2016-2017 Seminars

Tuesday, October 18, 2016

Dr. David Zimmerman
Office of Research Commercilization

TITLE:  SoCrates A Software and Creative Works Licensing Program at Rutgers


A growing number of schools are providing support for licensing and distribution of university-based software and copyrighted materials.  In addition to traditional success stories such as Stanford and MIT, schools such as Minnesota, New Hampshire, BYU, McMaster, and others have generated millions of dollars for their faculty, departments and schools through such licensing.

The SoCrates program is a new initiative at Rutgers Office of Research Commercialization (“ORC”) that will support the licensing and commercialization of other, non-patent-based types of IP such as content (creative works) and software.  In its early stages SoCrates is currently supporting the development, distribution and licensing of assets such as: apps, diagnostic questionnaires, enterprise software, videos, classroom teaching modules and as well as other assets.   Departments served by the SoCrates program include: GSAPP, School of Criminal Justice, Chemistry, SHRP, Food Science, NJ Medical School, and others.

Tuesday, October 11, 2016

Dan Russo and Nicole Revaitis
CCIB Students

RUSSO TITLE: CIIProCluster: Developing Predictive Toxicity Models Using Big Data

RUSSO ABSTRACT:  Accurate predictive computational models for complex toxicity endpoints, e.g. oral acute toxicity and hepatotoxicity, have remained elusive. The difficulties in model development for these endpoints can be attributed to the complex mechanisms relevant to the toxicity phenomena.  Recent work has shown that incorporating biological data into model development has resulted in better predictivity and allowed for intuition on mechanisms of action for toxicants. However, in the current big data era, finding and characterizing relevant biological data to evaluate the chemical toxicity of interest is a major challenge.  The Chemical In-vitro, In-vivo Profiling portal was created to use big data sources for the prediction of new compounds (ciipro.rutgers.edu). As a major advancement of the CIIPro project, we present CIIProCluster, a new approach for creating predictive toxicity models based on the available bioassay data for chemicals of interest. Briefly, all available biological data for the target compounds are automatically extracted. Chemical features relevant to each bioassay testing are identified by using Fisher’s Exact Test (p < 0.5) to rank chemical fragments existing in the target compounds of each bioassay dataset. The available bioassays can be clustered by the chemical fragment features that contribute to their activation.  In this study, PubChem bioassays were prioritized and clustered based upon the chemical-in vitro relationships described above for rat oral acute toxicity. Clusters of PubChem bioassays not only are able to predict acute toxicity for new compounds but also show toxicity mechanisms for toxicants containing the relevant chemical features. This new approach can be easily applied to generate predictive models for other animal toxicity endpoints.

REVAITIS TITLE:  The TGF-? like ligand, Gurken, controls the dynamics of EGFR activation during Drosophila oogenesis.

REVAITIS ABSTRACT:  The epidermal growth factor receptor (EGFR) signaling pathway is an essential regulator of tissue development across animals. During Drosophila melanogaster oogenesis, GRK is restricted around the oocyte nucleus, and activates a uniformly expressed EGFR in the overlaying follicle cells.  In several other Drosophila species, GRK distribution extends towards the posterior of the egg chamber, the precursor of the mature egg. The differences in GRK distribution among species is the mechanism underlying different activation patterns of EGFR, which are monitored by the diphosphorylated ERK (dpERK) in the follicle cells. These changes are responsible for the evolution of eggshell structures, including the respiratory tubes called dorsal appendages, and the lumen-like structure called the dorsal ridge. Combining experimental work and computational modeling, we aim to understand the mechanism controlling different distributions of GRK among species. This model encompasses several parameters of the EGFR signaling pathway.  The most novel of which is the dynamic positioning of the oocyte nucleus, which generates a transient signal across the overlaying follicle cells.  Other parameters include the rate of GRK diffusion, the internalization of the EGFR, and the effects of pathway’s inhibitors.  Using these parameters, we were able to model the distribution of GRK and EGFR activation. This model will be used to predict changes in the signaling network that can account for GRKs’ distributions.


Tuesday, October 4, 2016

Ashley Forsythe
Career Services, Rutgers-Camden

TITLE:  The Who, What, Where, When and How of Career Services.

ABSTRACT:  The Career Center is here is help you with all things related to your career goals; including the job/internship search, networking, and/or assistance continuing your education. An overview of Career Center services will help you to see what is available to you and what you may utilize in your journey. Job searching techniques and resources will also be discussed to help all students, especially those graduating or currently seeking a position.

Tuesday, September 27, 2016

Dr. Erol Akay
University of Penn

TITLE:  Social inheritance in animal social networks and its consequences

ABSTRACT:  The social network structure of animal populations has major implications for survival, reproductive success, sexual selection, and pathogen transmission of individuals. But as of yet, no process-based theory of social network structure exists that can explain the diversity of social networks observed in nature, and serve as a null model for detecting species and population-specific factors. In this talk, I will present a simple and generally applicable model of social network structure. In our model, network structure emerges from social inheritance, in which newborns are likely to bond with maternal contacts, and via forming bonds randomly. We compare model output to data from several species, showing that it can generate networks with properties such as those observed in real social systems. Our model demonstrates that important observed properties of social networks, including heritability of network position or assortative associations, can be understood as consequences of social inheritance. I will also present data from a long-term study on spotted hyenas in which we can quantify social inheritance directly.

Tuesday, September 20, 2016

Wenyi Wang
CCIB Student

TITLE:  Virtual Gold Nanoparticle Library: Simulation, Modeling and Experimental Validation


The use of nanomaterials in cosmetics, food and medicine has been sky-rocketing over the past decade. Experimentally designing biocompatible nanomaterials (e.g. featuring the desired bioactivities) is expensive and time-consuming. Computational modeling methods are expected to be able to predict biological activities of nanomaterials before chemical synthesis accurately. However, the current available approaches are either not applicable for nanomaterials or strongly unsatisfactory in terms of predictive performance due to the limitation of the existing modeling approaches and the complexity of nanomaterial structures. Here we designed and constructed a novel computational approach that can develop large virtual nanomaterial (i.e. nanoparticle) libraries to guide the future experimental studies. To this end, we first experimentally synthesized 34 Gold Nanoparticles (GNPs), which have different sizes and surface ligands, as the modeling set. Then we tested their hydrophilicity, HO-1 level in A549 cell line and cellular uptake against A549 cell line and HEK293 cell line. For these 34 GNPs, we virtually simulated their structures, calculated the chemical descriptors and developed Quantitative Nanostructure Activity Relationship (QNAR) models. The resulting QNAR models were firstly cross-validated by using the modeling set GNPs themselves, then used to predict and design new GNPs. Based on the prediction results, we synthesized seven new GNPs with new structures and tested them against the same four bioassays in the two cell lines. The high predictivity of the QNAR models, indicated by both cross-validation and external prediction, showed its capability for designing new GNPs. Therefore, with the virtual GNP library and experimental validation, we proved the feasibility and applicability of using computational modeling to greatly reduce the experimental cost of nanoscience. The development of virtual GNP library and the resulting QNAR approach paved the path to the new generation of nano-modeling and can be easily applied for designing biocompatible nanomaterials.

Tuesday, September 13, 2016

Catherine Rosenberg
Coriell Institute

TITLE:  Approaches to Calculating Limb Volume for Lymphedema Patients

ABSTRACT:  Lymphedema is a condition of localized fluid retention and tissue swelling caused by a compromised lymphatic system.  This is a condition that can sometimes be associated with post cancer treatments and has a greater possibility in occurring in patients that have been treated for breast cancer, gynecological cancers, or sarcomas.  However; lymphedema can develop with other types of cancer or patients can be born with the condition. Currently, there are a few surgical interventions available to assist patients in maintaining control of their edematous limb.  Therefore, it is imperative to be able to monitor each patient’s individual post-surgical progress.  To monitor the overall improvement from one of the surgical interventions a patient undergoes is extremely important and be done in various ways.  However, not all facilities have the equipment necessary to calculate the volume of a limb in identical ways.  Therefore, we looked at some possibilities that strictly use circumferential measurements to numerically calculate the volume of a limb.  These methods include using formulas associated with different geometric shapes. A mathematical model for the estimation of a true volume was generated using cubic splines for an initial comparison of volume calculations. The ultimate goal is to find the most accurate numerical formula with the least amount of error that computes the volume closely to both water displacement and the perometer, an optical-electronic device that is the new “gold-standard” for limb volume calculation.  Our numerical method of choice cannot rely on a specific number of intervals since every patient could potentially have a different number of cross sectional volume segments.


2015-2016 Seminars

Tuesday, April 26, 2016

Dr. Grace Brannigan
CCIB, Rutgers-Camden

TITLE:  Mechanisms of small molecule action on membrane proteins

ABSTRACT: Membrane proteins constitute about 60% of all drug targets, but the presence of a complex lipid bilayer around the native state of the protein dramatically increases the difficulty of determining structure and quantifying function, resulting in numerous obstacles to elucidating mechanisms of action of small molecules.   For many membrane proteins, both structure and function have a complex dependence on membrane composition that is difficult to characterize experimentally, originates in both direct interactions with lipids as well as indirect effects via the membrane, and is neglected in most drug-discovery tools. The family of pentameric Ligand-gated Ion Channels, including the GABA(A) receptor and nicotinic acetylcholine receptor (nAChR), are especially promising central nervous system targets that are also highly sensitive to lipid composition. Here I present results from a multi-pronged computational approach that aims to fully incorporate the unique properties of lipid bilayers into our understanding of the mechanisms underlying action of molecules such as anesthetics, neurosteroids, and thyroid hormone on the GABA(A) receptor and nAChR.

Tuesday, April 19, 2016

Dr. Laura Scheinfeldt
Coriell Institute

TITLE:  Challenges in translating GWAS results to clinical care

ABSTRACT: Several factors contribute to health-related quality of life, including: healthcare quality and access, individual behavior and lifestyle choices, environment, and genetics. The way in which genetic information can contribute to health-related quality of life can be further subdivided into the research component that focuses on understanding the underlying biology and inherited component of disease, and the implementation component that applies research knowledge in a clinical setting to improve health outcomes. Clinical genetic testing for Mendelian disorders is standard of care in many cases; however, it is less clear to what extent and in which situations clinical genetic testing will improve preventive efforts, diagnosis and/or prognosis of complex disease. One of the challenges in implementing clinical genetic testing in the management of complex disease is that much of the research reported to date relies on tag single nucleotide polymorphisms (SNPs) to act as proxies for assumed underlying functional variants that are not yet known. This assumption is especially problematic when reported studies do not include representative population samples, and the results are generalized across diverse populations. Here I will use the Coriell Personalize Medicine Collaborative (CPMC) as a case study to evaluate how well reported genetic risk variants for complex disease tag surrounding variants across population samples in the CPMC and in the 1000 Genomes Phase 3 data. I will also discuss the translational implications of simulated tag SNP performance.

Tuesday, April 12, 2016

Joseph Kawash
CCIB Student

TITLE:  Comparative Genome Analysis Utilizing Machine Learning Techniques

ABSTRACT: NGS has appeared as a powerful tool to query genotypes. It is widely used for genome re-sequencing allowing one to find differences between genomes especially between tumor/normal pairs. Identifying these mutations with acute confidence is key to being able to ascertain important differences. However, changes in sequencing methods or algorithm use can lead to widely varying output. Differing variety and amplitude of noise inherently present in the NGS data (from GC biases, PCR biases, sample heterogeneity, etc.) often hinders the ability to make accurate predictions. Traditional methods of detecting genome variations can become increasingly difficult to improve if greater consideration of feature variance and interactions are not taken into account. These interactions can be difficult to predict or account for when using simple filtering methods. Several possible factors may need to be considered under unique circumstances that increase algorithm complexity and cannot be easily accounted for manually. Presently we have begun to expand and test our existing algorithm with a machine learning module that utilizes gradient tree boosting. Machine learning provides an edge in creating a comprehensive set of parameters that are transferable between samples for analysis. These interactions and data transformations could be key to reliable prediction of calls through a wide range of sequencing conditions. We believe that by using publicly available validated data combined with machine learning we can identify the requisite key parameters and subsequent feature interactions of various mutation types. This enables us to create a robust algorithm that accurately detects genomic variants across differing genome samples. 

Tuesday, April 5, 2016

Sean McQuade
CCIB Student

TITLE:  Sensitivity of human Cholesterol Metabolic Networks, and Analysis of Cis-Regulatory Modules via Cell Lineage Asymmetry.

ABSTRACT: Two Projects will be discussed involving biological networks.  The first is an analysis of reaction pathways in human cholesterol metabolism, based on techniques from Bernhard Palsson’s, “Systems Biology”.  In the analysis, we find a stoichiometric matrix and use the kernel of this matrix to describe possible equilibria (sets of flows on the network which represent a Steady State).  We then perturb a given flow to determine the sensitivity of the flow on the network.  Our goal is to understand the nature of the network’s response to the perturbations.  We work in collaboration with the Translational Informatics department of Sanofi, a pharmaceutical company.

The second project is a theoretical analysis of a cell lineage.  We are testing an analytic method to infer spatial activity of Cis-Regulatory Modules(CRMs), based on the data provided by a specific experiment.  The experiment has been done before, and we believe an understanding of the spatial distribution of CRM activity can be obtained from this high throughput, quantitative data.  We combine two methods of limiting candidate cell groups that drive CRM expression.  The first method is called the “Probabilistic” method, and the second is called “Rank ordered profile reconstruction”.  The latter method implements a simulation of the cell Lineage of the organism to be tested.  In this case the organism is a Purple Sea Urchin. 

Tuesday, March 29, 2016

Min Kyung Min
CCIB Student

TITLE: E-Flux2 and SPOT: Validated Methods for Inferring Intracellular Metabolic Flux Distributions from Transcriptomic Data


Understanding how the activity of intracellular metabolic pathways changes in response to environmental or genetic perturbations is important to figure out how the living cell controls its metabolism and other cellular processes. Although intracellular metabolic flux (i.e. reaction rate) distributions are desirable information to this end, it is challenging to directly measure them. Several computational methods thus have been developed to predict system-wide and condition-specific intracellular metabolic fluxes by integrating transcriptomic data which is relatively easy to obtain, with genome-scale metabolic models. While powerful in many settings, existing methods have several shortcomings, and it is unclear which method has the best accuracy in general because of limited validation against experimentally measured fluxes.

 We developed a general optimization strategy for inferring intracellular metabolic flux distributions from transcriptomic data coupled with genome-scale metabolic reconstructions. It consists of two different template models called DC (determined carbon source model) and AC (all possible carbon sources model) and two different new methods called E-Flux2 (E-Flux method combined with minimization of l2 norm) and SPOT (Simplified Pearson cOrrelation with Transcriptomic data), which can be chosen and combined depending on the availability of knowledge on carbon source or objective function. 

 The predictive accuracy of algorithm was then validated by calculating the Pearson correlation between predicted fluxes and measured fluxes. To this end, we compiled 20 experimental conditions (11 in E. coli and 9 in S. cerevisiae), of transcriptome measurements coupled with corresponding central carbon metabolism intracellular flux measurements, which is the largest dataset assembled to date. In both organisms, our method outperformed a representative sample of competing methods. 

 In several collaborative research, our method has been used to help better understand differences in metabolism among cells, each of which is with a phenotype of interest. Easy-to-use implementations of E-Flux2 and SPOT are available as part of the open-source package MOST (http://most.ccib.rutgers.edu/).

Tuesday, March 22, 2016

Dr. Michael Levine
Princeton University

TITLE:  Computational and quantitative analysis of animal enhancers.

ABSTRACT:  Enhancers are short segments of DNA, typically 50-500 bp in length, that activate and repress gene expression in response to a variety of intrinsic and external signals.  The human genome is thought to contain ~1 million enhancers, and sequence polymorphisms in these enhancers are thought to be a major source of population variation and predilection to disease.  I will discuss several basic properties of enhancers, based on live-imaging studies in Drosophila and high throughput assays in the protovertebrate, Ciona.  Several topics will be considered, including the regulation of transcriptional bursts, and the suboptimization of developmental enhancers mediating tissue-specific patterns of gene activity. 

Tuesday, March 8, 2016

Dr. Alicia Ebert
University of Vermont

TITLE:  FGF8 signaling is required for proper vascularization of the zebrafish retina

ABSTRACT:  Fibroblast growth factors (FGFs) are critical in many aspects of embryonic development and other cellular functions including apoptosis, cell adhesion, and proliferation. FGF8a, specifically, is known to work in coordination with FGF3 to initiate retinal ganglion cell (RGC) differentiation (Martinez-Morales et al., 2005). We identified FGF8a mRNA expression in the RGCs themselves a day after differentiation. Inhibition of FGF8 using the acerebellar (ace) mutant zebrafish, we show a decrease in retinal proliferation leading to smaller eyes. We also identified FGFR1b expression in the adjacent vascular tissue. Inhibiting FGFR1b with an antisense morpholino led to a phenocopy of FGF8 mutants. Loss of either the ligand (FGF8) or the receptor (FGFR1b) led to mispatterned retinal vasculature with decreases in blood flow through the eye. Our working model is that FGF8 secreted from the RGCs stimulates vascularization in the retina allowing for nutrient provisions to the developing nervous tissue. This neurovascular interaction is unique and has not been previously described in the retina.

Tuesday, February 23, 2016

Daniel Pinolini
CCIB Student

Title: Melatonin Synthesis Pathway in Neurospora Crassa

Abstract: Melatonin is a hormone that has been shown to be secreted rhythmically and anticipates the daily onset of darkness, and its receptors have been shown to play a major role in the treatment of various sleep disorders. While the synthesis and response pathways are fairly well characterized in humans, little to no research has been done to characterize the same pathways in the model organism Neurospora crassa. Previous research has, however, revealed that melatonin is secreted in N. crassa. Preliminary data has shown that exposure to melatonin in constant conditions elicits the same effect on observable circadian rhythm in N. crassa as previously demonstrated in humans. It is hoped that through further research, this circadian effect can be confirmed, the fungal melatonin synthesis and response pathways can be characterized in N. crassa, and that the model organism Neurospora crassa can be established as a viable testing ground for new pharmaceutical compounds for the melatonin receptor related treatment of various sleep disorders.

February 16, 2016

Dr. Kyung-Jae Won
University of Pennsylvania

Title: Finding Orders in Heterogeneity: Studying X Chromosome Inactivation using Single Cell Transcriptome

Abstract: We studied X chromosome inactivation (XCI) during the human embryonic cell (hESC) differentiation using single-cell transcriptomic data. Cells were collected in hESCs and the differentiated cells by treating ESCs with BMP4 (Diffs). As expected, the expression levels of the master regulator (Oct4, Sox2, and Nanog) in ESCs were reduced drastically in Diffs. Interestingly, the expression level of Xist, a long intergenic non-coding RNA that controls XCI, was not correlated well with these master regulators. Classifying genes based on the Xist expression levels, we found a group of genes that are potentially regulated by Xist in ESCs. More importantly, we observed that many genes including the genes known to subject to XCI were not entirely inactivated in the inactivated X chromosome. Our analysis using single cell transcriptomic data expanded our knowledge about XCI.  In addition, I present a study about pancreatic cell development using single cell transcriptomic data.

Tuesday, February 9, 2016

Dr. Brad Davidson
Swarthmore College

Title: Mitotic membrane turnover: inscribing heart cell fate during division.

Abstract: Cell fate decisions can be impacted by trafficking of signal components. Recent studies have overturned the long-held assumption that trafficking is shutdown during mitosis. Thus, mitotic trafficking of signaling components may play a profound, largely unrecognized role in embryonic and stem cell fate. We have gained significant insights regarding the interplay between division and signaling by examining embryonic development in the basal chordate, Ciona intestinalis. The extreme cellular simplicity of Ciona embryos facilitates high-resolution, in vivo analysis of inductive signaling mechanisms. In particular, we focus on Fibroblast Growth Factor (FGF) dependent induction of the heart progenitor lineage. We have found that mitotic redistribution of FGF receptors (FGFRs) promotes differential heart progenitor induction. We are currently investigating the role of mitotic kinases in FGF receptor localization. 

Tuesday, February 2, 2016

Catherine Guay
CCIB Student

TITLE: Functional adaptation of the maternal skeleton to reproduction and lactation

Tuesday, January 26, 2016

Dr. Xaiowei Sherry Liu
University of Pennsylvania

TITLE: Functional adaptation of the maternal skeleton to reproduction and lactation

ABSTRACT:  The maternal skeleton serves as an important source of calcium for fetal/infant bone growth and undergoes substantial changes during pregnancy and lactation. Despite a substantial increase in bone formation following weaning, bone mass is only partially restored. However, most epidemiology studies report that the number of pregnancies and the duration of lactation have either no long-term adverse effect, or have a positive effect on fracture risk later in life. This represents a paradox that reproduction and lactation reduce bone mass without increasing future risk of fractures. To uncover the mechanisms behind this paradox, we compared the mechanical integrity between the highly load-bearing bone regions and other sites post-lactation, and demonstrated reduced bone loss and more efficient recovery in the load bearing vs. non-load bearing region. Furthermore, although post-lactation rats have lower bone mass than virgin rats, they have a distinct bone structural phenotype and a much slower rate of bone loss when exposed to estrogen deficiency by ovariectomy (OVX). These discoveries suggested that skeletal changes that occur during reproduction and lactation represent a physiological adaptation of bone structure, which minimizes the impact of reproduction on the skeleton’s mechanical function and prepares the skeleton to be more resistant to estrogen deficiency induced bone loss later in life. These amazing adaptive mechanisms in bone may help to protect the maternal skeleton from future menopausal bone loss.

Tuesday, December 8, 2015

Spyros Karaiskos
CCIB Student

TITLE: Transfer RNA-derived fragments in Drosophila and their potential targets

ABSTRACT: We present rather unusual suspects in the world of gene regulation–transfer RNA fragments (tRFs). Such fragments have previously escaped detection or have been generally ignored as noise due to low count numbers in of small RNA libraries. While the focus in the analysis of such libraries has been primarily on microRNAs (miRNAs), recent studies have reported findings of fragments of transfer RNAs (tRFs) across a range of organisms. We had originally investigated the age-related dynamics of miRNA loading into different RNA-induced silencing complexes (RISC) of Drosophila melanogaster using small RNA-Seq. Here we describe tRFs found in the same transcriptome libraries, and focus on their structural and functional features that make these fragments similar to miRNAs. Similar to miRNAs tRFs have distinct isoforms with precise ends preferentially originating from 5′ or 3′ end of a precursor molecule (tRNA). Analogously to the seed sequences in miRNAs, we observe that tRF ends possess short 7-mer sequences matching conserved regions across 12 Drosophila genomes, preferentially in 3′ UTRs but also in introns and exons. Like miRNAs, tRFs display specific isoform loading into Ago1 and Ago2 and thus likely function in RISC complexes. And finally, as is the case with miRNAs, we observe the levels of tRF loading into Ago1 and Ago2 to differ considerably and both tRF expression and loading appear to be age-dependent, indicating potential regulatory changes from young to adult organisms. We found that Drosophila tRF reads mapped to tRNA genes for all 20 amino acids, while previous studies have usually reported fragments from only a few tRNAs. Moreover, we detected fragments of both nuclear and mitochondrial tRNAs, while only the former have been described. Following the similarities with miRNAs and based on complementarity with conserved Drosophila genome regions we described seed sequence found in the most abundant tRFs. Further, we identified their possible targets with matches in the Drosophila melanogaster 3’UTR regions. Strikingly, these potential target genes of the most abundant tRFs show significant Gene Ontology enrichment in development and neuronal function. This observation suggests that involvement of tRFs in the RNA interfering pathway may play a role in brain activity or brain changes with age.

Tuesday, December 1, 2015

Dr. Robert Best
National Institutes of Science

TITLE: How well do atomistic simulations of folding compare to theoretical expectations, and to experiments?

ABSTRACT:  It has recently become possible to perform all-atom molecular simulations, in explicit solvent, of proteins folding and unfolding at equilibrium. These unbiased trajectories provide a ‘movie’ of protein folding which can be used to test directly the assumptions made in developing theoretical models for folding. I will discuss two such assumptions, firstly that only native contacts are important in determining folding mechanism, and secondly that folding can be modeled as diffusion on a low-dimensional free energy surface. We can also ask how well the results of the simulations agree with experimental data. To this end, we have developed a method for obtaining protein folding phi-values from simulation, allowing us to test the observed mechanism against experiment. We find reasonable agreement in many cases, but a surprising heterogeneity in folding mechanism is hidden by the ensemble-average phi-values.

Tuesday, November 24, 2015

Dr. Tianhai Tian
Monash University

TITLE: Simplified model for molecular process of multi-step reactions

ABSTRACT: Many molecular processes include a number of detailed chemical reactions. Example of this type process include gene transcription, translation and molecule degradation. Currently these multi-step reactions are modelled by a single step reaction or chemical reaction with time delay. However, numerical results suggest that these models cannot describe multi-step process accurately. In this work we will discuss two new methods for modelling multi-step reactions.

Tuesday, November 17, 2015

Dr. Marc Halfon
University of Buffalo

TITLE: Regulatory Genomics of Model and Non-Model Organisms

ABSTRACT:  Regulation of gene expression is essential for proper metazoan development and homeostasis, yet our knowledge of regulatory DNA sequences—transcriptional cis-regulatory modules (CRMs)—is strikingly limited. This is particularly true for non-model organisms, in which the reagents and resources necessary for large-scale CRM discovery are often lacking. We have developed the SCRMshaw algorithm, which leverages extensive available knowledge of Drosophila regulatory sequences to enable CRM discovery in both closely and distantly related insects. SCRMshaw has great potential for studying the regulatory genomics of both model and non-model organisms, including enabling rapid annotation of the regulatory genomes of newly-sequenced insects, distinguishing between divergent and convergent regulatory sequence evolution, and understanding the mechanisms underlying the evolution and neofunctionalization of developmental regulatory networks.

Tuesday, November 10, 2015

Yinghui Zhong
Drexel University

TITLE:  Metal ion binding-mediated drug delivery mechanism

ABSTRACT:  We developed a novel drug delivery mechanism: metal ion binding-mediated interaction for sustained release of hydrophilic small molecule drugs with high metal ion binding affinity. Minocycline Hydrochloride (MH) is a tetracycline derivative antibiotic with anti-inflammatory, anti-oxidative, and anti-apoptotic properties. Moreover, it has demonstrated great therapeutic potential in treating debilitating spinal cord injury and neurodegenerative diseases. MH can chelate divalent metal ions such as Ca2+ and Mg2+ ions which can enhance its stability in aqueous environment without affecting its biological activities. Dextran sulfate (DS) is a biodegradable polysaccharide that also has a high binding affinity for Ca2+ and Mg2+ ions. We found that the metal ions can be used as the linkers to attach MH to DS molecules. Utilizing this property, we have developed two drug delivery systems: layer-by-layer (LbL) thin film coatings and self-assembled insoluble complex for sustained release of MH. We will discuss the potential mechanisms that mediate the interactions between DS, MH and metal ions, which lead to the complex formation between a charged polymer and a neutral small drug molecule. We will also discuss the application of these complexes in spinal cord repair.

Tuesday, November 3, 2015

Sweta Sharma
CCIB Student

TITLE:  Empirical Evidence Supporting a Systematic Approach to Gene Network Identification

ABSTRACT:  A major cellular systems biology challenge of the past decade has been the development of a comprehensive model for gene regulatory networks (GRNs). Particularly, there is growing impetus for the extraction of regulatory information from expression data as it becomes increasingly available and accurate. Identifying networks from such information requires deciphering direct interactions from indirect ones. For instance, if gene A regulates gene B and B regulates gene C, then changing A’s expression will directly affect B’s expression while indirectly affecting C’s.

Recently, Birget et al proposed a systematic approach for network identification. They consider a binary model that captures the non-linear dependencies of GRNs and reverse-engineer the network using assignments (perturbations to the expression level of a single gene) and whole transcriptome steady-state expression measurements. Under this model, their approach achieves identification of acyclic networks with worst-case complexity costs in terms of assignments and measurements that scale quadratically with the size of the network. For networks with cycles, the worst-case complexity cost scales cubically. 

We conduct a proof-of-concept experiment for this approach by reverse-engineering a five-gene sub-network of the outer-membrane protein regulator (ompR) in E. coli. Through assignments achieved by gene deletions and expression measurements from qPCR, we successfully identify the regulatory relationships and discern direct from indirect interactions. We also performed computational experiments on in silico networks derived from known regulatory relationships in E. coli and S. cerevisiae, where gene regulation is thermodynamically modeled using the system of ODEs that was used to generate data for previous DREAM challenges. We achieve 100% identification for noiseless acyclic networks of size ranging from 100 to 4,000 genes. For noisy acyclic E. coli networks of size 100, we obtain an AUPR of .95. This is significantly improved from the .71 AUPR obtained by the top performer in the DREAM3 inference challenge for acyclic in silico networks. Furthermore, we achieve this using ten-fold fewer assignments and measurements. For noisy cyclic E. coli networks of size 100, we obtain an AUPR of .75, compared to .45 for the top performer in the DREAM4 InSilico_Size100 sub-challenge containing cyclic networks. We achieve this using roughly the same number of assignments and half as many measurements. 

Taken together, our results imply that the reverse engineering method of Birget et al is not only experimentally feasible but uses reasonable resources. It can therefore serve as the basis for systematic, accurate reverse engineering of large-scale gene regulatory networks.

Tuesday, October 20, 2015

Dr. Jia Song
University of Delaware

TITLE: microRNA cross-regulation of signaling pathways

ABSTRACT:  In early development, cell specification and pattern formation are controlled by cross-regulation of gene regulatory networks (GRN) and signaling pathways. Signaling morphogen gradients are critical regulators that need to be tightly controlled in order to ensure that the precise organization of the embryo is achieved. This research addresses the overarching hypothesis that microRNAs (miRNAs) perform this critical regulatory function. The miRNAs are small non-coding RNAs that repress the translation and reduce the stability of target mRNAs in animal cells. microRNA-31 (miR-31) has been found to play a role in cancer, bone formation, and lymphatic development. However, the function of miR-31 in embryogenesis is not known. We examined the regulatory role of miR-31 in early development of the sea urchin.  We found that miR-31 is expressed in all stages of development and its knockdown (KD) results in decrease in embryo size, formation of extra cells and cell clumps in the blastocoelar space of the embryo and disrupts the patterning and function of the primary mesenchyme cells (PMCs), which form the embryonic skeleton spicules. Using bioinformatics approach and luciferase reporter constructs, we identified miR-31 to repress directly Pmar1, Alx1, Snail and VegfR7 within the PMC GRN. Further, blocking the miR-31-mediated repression of Alx1 and/or VegfR7 genes in the developing embryo resulted in defects in PMC patterning and skeletogenesis. The majority of the mislocalized PMCs in miR-31 KD embryos did not express VegfR10, indicating that miR-31 regulated VegfRs within the PMCs. In addition, miR-31 indirectly suppresses Vegf3 expression in the ectoderm. These results indicate that miR-31 coordinately suppresses genes within the PMCs and in the ectoderm to impact PMC patterning and skeletogenesis.

Tuesday, October 13, 2015

Dr. Sean Ekins
Collaborative Drug Discovery

TITLE: Open Science for Rare and Neglected Diseases

ABSTRACT: As a computational scientist I have been fortunate to work with many collaborators to generate biological data to train and test my models. We are in a position with increasing amounts of data becoming accessible in the public domain to generate models and predictions relevant to finding molecules for many diseases. For example databases like ChEMBL and PubChem become a potential goldmine when combined with computational algorithms that can be applied quickly to identify new molecules to test. Over the past 8 years I have made extensive use of public datasets for screening against M. tuberculosis, T. Cruzi, responsible for tuberculosis and Chagas disease, respectively. This work has lead to collaborators testing a small number of compounds and finding novel actives. This approach is more broadly applicable to other diseases. The subsequent publication of the models and molecules into the public domain has also been addressed by developing tools on the desktop which can enable the sharing of machine learning models, and use on mobile devices. Many of the lessons learned have also been applied to work on rare diseases. For example, utilizing some of the high throughput screening data generated to identify inhibitors of the Ebola virus has been used to create machine learning models to find new molecules not previously tested. For many rare diseases there are huge data gaps and other approaches need to be taken. In spite of the many incentives offered it is likely most of the rare diseases do not present big commercial opportunities and hence there is definitely a place for more openness and collaboration to bring ideas from the lab to the clinic quickly.

Learning objectives: 1. Demonstrate how open data can be used to create models, identify new leads and how this is increasingly accessible to anyone 2. Describe experiences working on rare and neglected diseases and what could be done to increase success in bringing ideas to the clinic.

Tuesday, October 6, 2015

Wenyi Wang 
CCIB, Rutgers-Camden

TITLE: Quantitative Nanostructure Toxicity Relationship

ABSTRACT: The toxicity of nanomaterials has become a major concern due to its increased usage in a variety of applications (e.g., electronics, cosmetics, and medicine). Nanoparticles have different sizes, shapes, chemical compositions and surface modifications, making it difficult to simulate the toxicity as opposed to small organic compounds. Furthermore, there is a lack of comprehensive data and standardized toxicity endpoints on nanoparticles necessary for modeling the toxicity of compounds. I gathered and curated several data points related to nanotoxicity, along with the crucial parameters mentioned above. Using the datasets, I aim at designing Quantitative Nanostructure Toxicity Relationship (QNTR) approaches to develop validated and predictive models. Specifically, I will develop novel approaches to calculate the surface properties, as well as overall chemical properties of nanoparticles, integrate the various parameters with the conventional Quantitative Structure-Activity Relationship (QSAR) modeling process and publish the predictors. The novel approaches will be applicable to various nanomaterials and endpoints, while the established models and predictors will be used to prioritize potentially toxic nanomaterials. 

Tuesday, September 29, 2015

Daniel Russo
CCIB, Rutgers-Camden

TITLE: CIIPro:  An online cheminformatics portal for large scale chemical data analysis

ABSTRACT: The massive amount of chemical data that currently exists in this big data era is difficult to extract and hard to rely on.  To this end, we developed a public Chemical In vitro In vivo Profiling (CIIPro) portal that can automatically extract biological data from public resources (i.e., PubChem) for compounds based on user input.  Unlike querying a typical chemical database, a novel algorithm in the portal allows users to query compounds with a target activity (e.g., specific animal toxicity testing results), extracts biological data based on the in vitro-in vivo correlation, and outputs the data in a format conducive to research.  The resulting biological data for target compounds can be used for modeling purposes.  For example, the CIIPro portal can identify the chemical and biological similarity between compounds based on their chemical structure and optimized biological profile.  This portal was used to develop multiple novel predictive models for complex biological activities (e.g., complex animal toxicity endpoints).  The CIIPro portal is free and accessible through the internet at ciipro.rutgers.edu

Tuesday, September 22, 2015

Nicole Pope
University of Pennsylvania

TITLE:  The TGF-? like ligand, Gurken, shapes the formation of dorsal eggshell structures in Drosophila species

ABSTRACT: The epidermal growth factor receptor (EGFR) signaling pathway is an essential regulator of tissue development across animals.  In Drosophila melanogaster, the EGFR ligand, Gurken (GRK), is a central regulator of dorsal ventral and anterior posterior axes formation. During Drosophila oogenesis, gurken is restricted around the oocyte nucleus.  The nucleus positions are dynamic, initially at the posterior end, and later it moves to a dorsal position. Consequently, the combination of nuclear movement and ligand secretion, generates a transient signal in the overlaying follicle cells through a uniformly expressed receptor. The follicle cells form the 3D eggshell structures, including the respiratory filaments, the dorsal appendages, and the lumen-like dorsal ridge. These structures reflect the numerous signaling pathways’ activities, including EGFR. Interestingly, the pattern of EGFR activation is different among Drosophila species. These patterns are consistent with GRK’s distribution and are consistent with the different positions and shapes of eggshell morphologies. The sequence of GRK is highly evolved among species. We hypothesize that changes in the GRK protein enable different persistence of the ligand, which control the length of the transient signal, and consequently the formation of the corresponding morphologies. Using experimental and computational tools, we are studying the mechanisms underlying GRK distributions among species.

Tuesday, September 15, 2015

Dr. Feng Gai
CCIB, Rutgers-Camden

TITLE:  Probing Protein Hydrogen Bonding Dynamics via 2D IR Spectroscopy

ABSTRACT: Hydrogen bonds (HBs) play a critical role in determining the structure, function and folding dynamics of proteins.  In this talk, we will discuss how linear and nonlinear infrared spectroscopic methods, in conjunction with unnatural amino acid-based infrared probes, can be used to study the dynamics of such HBs in a site-specific manner.


2014-2015 Seminars

Tuesday, April 28, 2015

Robert Marmion
Rutgers University-Camden

TITLE:  Wishful thinking is regulated by a P-MAD binding site that varies among Drosophila species

ABSTRACT: The Drosophila eggshell is an established model to study cell signaling, tissue patterning, and morphogenesis. The bone morphogenetic protein (BMP) signaling pathway is a crucial regulator of tissue growth during multiple stages of Drosophila development. We found the type II receptor, wishful thinking (wit), to be dynamically and non-uniformly expressed in the follicle cells, which are a mono-layer of epithelial cells engulfing the developing oocyte.  wit is transcriptionally regulated by BMP signaling and necessary for BMP signal transduction within the follicle cells. We studied gene regulation by BMP via studying the cis-regulatory module (CRM) responsible for wit expression.  Here we describe a binding site for P-MAD, the transcription factor of the BMP pathway, which differs from the literature description.  We utilized D. virilis, a species separated by 45 million years of evolution from D. melanogaster.  Interestingly, wit patterning differs both in width and dynamics.  We recapitulated this pattern in D. melanogaster by expression driven by the homologous CRM.  We suggest that spacing between MAD & MED binding sites underlies the patterning differences.

Tuesday, April 21, 2015

Dr. Lan Yang
Washington University

Title: Whispering-Gallery Microresonators and Microlasers for nanoscale sensing and beyond

Abstract:  Optical sensors based on Whispering-Gallery-Mode (WGM) resonators have emerged as front-runners for label-free, ultra-sensitive detection of nanoscale materials and structures due to their superior capability to significantly enhance the interactions of light with the sensing targets. A WGM resonator traps light in circular orbits in a way similar to a whisper, i.e., a sound wave, traveling along a circular wall, an effect found in the whispering gallery of St. Paul’s Cathedral in London. The basis for resonator sensors is that the physical associations and interactions of nanomaterials on the surface of a high-Q optical WGM resonator alter the trajectory and lifetime of photons in a way that can be measured and quantified. I will first present a laser-assisted processing method to create Si-chip based optical microresonators with Q-factors in excess of 100 million. Sol-gel process will be introduced as a convenient and efficient method to incorporate optical gain dopants into the oxide layer deposited on a silicon wafer, providing a route to achieve arrays of microlasers on silicon wafer with emission spectral windows from visible to infrared. I will then present a recent discovery of using ultra-high-Q microresonators and microlasers for ultra-sensitive self-referencing detection and sizing of single virion, dielectric and metallic nanoparticles. I will also discuss using optical gains in a microlaser to improve the detection limit beyond the reach of a passive microresonator. These recent advancements in WGM microresonators will enable a new class of ultra-sensitive and low-power sensors for investigating the properties and kinetic behaviors of nanomaterials, nanostructures, and nanoscale phenomena. In the end, I will discuss exploration of fundamental physics, such as parity-time symmetry and light-matter interactions around exceptional point (EP) in high-quality WGM resonators, which can be used to achieve a new generation of optical systems enabling unconventional control of light flow.

Tuesday, April 7, 2015

Marlene Kim
Rutgers University-Camden

TITLE:  Mechanism Profiling of Hepatotoxicity Caused by Oxidative Stress Using the Antioxidant Response Element Reporter Gene Assay Models and Big Data Sources 

ABSTRACT: Hepatotoxicity accounts for a substantial number of drugs withdrawn from the market. Traditional animal models used to detect hepatotoxicity are expensive and time consuming.  Alternative in vitro methods, especially cell-based high-throughput screening (HTS) studies, have provided the research community with rich toxicity data.  Among the various assays used to screen potential toxicants, the Antioxidant Response Element beta lactamase reporter gene assay (ARE-bla), which identifies chemicals that have the potential to induce oxidative stress, has been used to test over 10,000 compounds from the Tox21 program.  The ARE-bla computational model and HTS data from big data sources (e.g., PubChem) were used to profile environmental and pharmaceutical compounds with hepatotoxic data.   Quantitative Structure-Activity Relationship models were developed based on ARE-bla data.  The models predicted the potential oxidative stress response for known liver toxicants when there was no ARE-bla data available.  Liver toxicants were used as probe compounds to search PubChem Bioassay and generate a response profile, which contained thousands of bioassays (>10 million data points).  By ranking the in vitro-in vivo correlations (IIC), the most relevant bioassay(s) related to hepatotoxicity were identified.  The liver toxicants profile contained the ARE-bla and relevant PubChem assays.  Toxicity pathway maps for well-known toxicants were created by identifying chemical features that existed only in compounds with high IIC.  The chemical IIC profiling created an opportunity to fully explore the source-to-outcome continuum of modern experimental toxicology using cheminformatics approaches and big data sources.

Tuesday, March 31, 2015

Nastassia Pouradier Duteil
Rutgers University-Camden

TITLE:  Modeling Gurken and dpERK distributions in Drosophila melanogaster oogenesis.

ABSTRACT: Tissue patterning and cell fate determination are guided by a multitude of cell signaling pathways working independently and in cooperation. At this level of complexity, computational simulations can serve as an efficient tool to narrow down potential mechanisms. We study tissue patterning in Drosophila, which is a commonly used model organism for cell signaling, tissue patterning, and morphogenesis. More specifically, we aim to understand the mechanisms leading to the formation of a particular eggshell structure, the dorsal ridge. The dorsal ridge is present with various lengths in the species D. nebulosa and willistoni, and is absent in D. melanogaster. It has been shown that the distribution of the TGF-alpha like ligand Gurken in the egg chamber, the precursor to the mature eggshell, is not only consistent with the patterns of the eggshell structure, it is also responsible to mediate dorsal ridge formation. We propose a mathematical model to explain the evolution of the Gurken distribution during oogenesis in D. melanogaster. Gurken is secreted from near the oocyte nucleus into the perivitalline space surrounding the oocyte. It then binds to the EGF receptors in the overlying follicle cells, internalizes, and initiate a signaling cascade of phosphorilations monitored by dpERK. These processes occur over the course of ~27h, during which the Drosophila egg chamber undergoes morphological changes, including the relative movement of the oocyte nucleus with respect to the follicle cells, and the considerable growth and elongation of the oocyte. Previously, the diffusion of Gurken was modeled to determine its impact on follicle cells’ patterning, however, the dynamics of oocyte nucleus location was not considered. Our contribution is to consider the oocyte nucleus as a moving source of Gurken. We are also developing a mathematical framework that will allow us to account for the growth of the oocyte.

Tuesday, March 24, 2015

Sruthi Murlidaran
Rutgers University-Camden

TITLE:  Effects of genetic variance and general anesthetics on ligand gated ion channels.

ABSTRACT: GABA(A) receptors are critical for proper transmission of inhibitory signals in the central nervous system, and are common targets of anesthetics, neurosteroids and thyroid hormone. Several naturally occurring mutations in such receptors can cause an increased likelihood of seizures.

Molecular Dynamics simulations with atomic resolution were conducted on a GABA(A) receptor model based on the GluCl template, including a single nucleotide polymorphism (SNP) K289M associated with increased likelihood of febrile seizures.  Receptors with the K289M SNP had statistically significant differences in numerous conformational variables, including pore radius. From these results we propose a molecular mechanism for rapid but unstable closure of GABA(A) receptors, which would be likely to cause the flickering effect reported  in single channel recordings.  Mechanisms underlying modulation were also investigated using Molecular Dynamics simulations. Photoaffinity labeling and mutagenesis studies have suggested numerous potential binding sites for modulators of GABA(A) receptors such as general anesthetics and neurosteroids, but relative affinities of the modulators for the individual sites are challenging to characterize experimentally. Molecular dynamics simulations and the alchemical free energy perturbation technique were used to calculate the isolated affinities of general anesthetics such as propofol and sevoflurane, for the intersubunit sites in the transmembrane domain.

Tuesday, March 10, 2015

Dr. Curt Breneman
Dean, School of Science
Rensselaer Polytechnic Institute

TITLE:  “A Fast Tour of Predictive Cheminformatics: From Drug Discovery to Materials Informatics.”

ABSTRACT:  Given the data rich environment present in many fields of study, it has become imperative to develop methods and “Best Practice” workflows that can extract information from these data repositories that enable “Data to Action” design strategies.  Some of the first major efforts in this area took place in the domain of drug discovery, where many mistakes were made and lessons were learned that now serve us well within that original field as well as in bioinformatics and materials informatics applications.  This presentation will emphasize the principles involved in developing and validating data-driven models that incorporate “just enough physics” to have meaningful domains of applicability.  Examples and anecdotes will be plentiful… 

Tuesday, March 3, 2015

Mr. Vincent Smeraglia
Executive Director, Strategic Alliances
Office of Translational Sciences

TITLE: What is Translational Sciences?

ABSTRACT: Rutgers Translational Sciences (RTS) is designed to assist biomedical research faculty create and build interdisciplinary collaborations. RTS connects intellectual property, marketing and contracts capabilities to build strategic alliances with the private sector. By providing access to facilities and expertise in molecular design and synthesis, nonclinical imaging, histopathology and toxicology, drug discovery screening, structural biology and related technologies, RTS is committed to meeting the needs of university and industry collaborators.

February 24, 2015

Sweta Sharma
Rutgers University–Camden

TITLE: Empirical Evidence Supporting a Theoretical Approach to Gene Network Identification

ABSTRACT: An important challenge in systems biology is the reverse engineering of biological networks. For gene regulatory networks, expression profile data for networks under various conditions are often used to identify regulatory interactions. Predictions from the best-performing existing network inference methods are plagued with low accuracy, often due to an inability to discern direct from indirect interactions. Recently, a theoretical model has been proposed to ascertain whether expression data is sufficient for identifying the network and, if so, how many single-gene perturbations (assignments) and whole-genome expression profile measurements are necessary. They show that for an n gene network, identification can be achieved with quadratic complexity in terms of these assignments and measurements.

Using a five-gene sub-network of the E. coli K-12 strain, we show in vivo evidence of the models effectiveness in discerning direct from indirect interactions. We also perform computational experiments on dynamical in silico E.coli and S. cerevisiae sub-networks generated by the same method as those used for previous DREAM challenges. Networks were probed by making assignments, specifically modifying the expression value of a gene to a fixed value, and then measuring the corresponding steady-state expression profile. Assuming no molecular or experimental noise, we achieve 100% identification for networks of size ranging up to 4,000 genes. We further assess performance with varying model assumptions such as additive Gaussian noise in the expression data and the presence of cycles in the network. For a 100-gene network with noise, we achieve an AUPR of .95 using ten-fold fewer assignments and measurements as compared to the DREAM3 top performer (AUPR .75).

February 17, 2015

Dr. Luis Cruz Cruz
Associate Professor, Physics Department
Drexel University

TITLE: Possible Connection between Neuronal Locations and Network Firing Patterns: A Computational Approach

ABSTRACT:  In normal aging, our brains suffer from progressive loss of function expressed as a gradual deterioration in memory, learning, and concentration. This is an important scientific and social problem as an increasingly larger percentage of our population ages.  The causes of this cognitive decline remain unclear and cannot be assigned to any particular mechanism, unlike neurodegenerative disorders such as Alzheimer’s disease where the cause of progressive cognitive impairments is the massive and progressive loss of cortical neurons.  However, normal aging causes subtle alterations in positional correlations between neurons in some brain areas, specifically within microcolumns: arrays of interconnected neurons which may constitute fundamental computational units in the brain.  This age-related loss of correlations is hypothesized to be a result of subtle deteriorating processes that change the underlying organization of the neuronal architecture and that may affect network firing dynamics.  Using a dynamical model applied to virtual 3D representations of neuronal arrangements, micron-sized random displacements in neuronal positions are shown to account for the experimentally measured loss of

organization in aged brains and to correlate with age-related cognitive decline.  In addition, by using an empirically-based computational framework, a connection between neuronal positions, topology of connectivity, and network firing dynamics will be presented.         

February 10, 2015

Harish Swaminathan
Rutgers University-Camden

TITLE: Computational methods for the interpretation of forensic DNA samples

ABSTRACT: Repetitive sequences in the human genome called Short Tandem Repeats (STRs) are used in human identification for forensic purposes. An STR profile developed from a biological sample collected at a crime scene is compared with that of a person of interest or run against a database to check for a match. Interpretation of STR profiles is problematic because of dropout, allele overlap and PCR amplification artifacts like stutter. The goal of this research is to develop computational methods and tools for analysis of STR profiles that are robust to these phenomena and that utilize quantitative peak height information captured in profiles. These methods are expected to improve significantly on existing methods for analysis of STR profiles, particularly in cases of low amounts of template DNA or where there are many contributors. The first aim of this research is to characterize the signal, noise and stutter peak heights and study their dependence on template DNA amount. Our second aim is to develop a method to identify the number of contributors (NOC) to a DNA sample. We developed a computational method called NOCIt that calculates the a posteriori probability (APP) on the number of contributors to a forensic sample. NOCIt takes into account signal peak heights, population allele frequencies, allele dropout and stutter. Among the samples tested, NOCIt had a higher accuracy than two of the existing methods to determine the NOC. The ultimate objective of mixture interpretation is to determine whether a person of interest contributed to the sample. Though methods have been developed to tackle this problem by deconvolving mixtures, they are generally not suitable for complex mixtures that contain significant amounts of dropout, stutter and allele sharing. Our third aim is to develop a computational tool (MatchIt) to directly calculate the LR for a person of interest and to compute a p value for the LR.

Tuesday, February 3rd

Dr. Joel Freundlich
Rutgers University–Newark

TITLE: A Novel Intersection of Computation, Chemistry, and Biology in the Study of Tuberculosis

Tuberculosis, due to Mycobacterium tuberculosis infection, represents a global health pandemic. New drugs are needed to combat resistance to existing therapeutics, mycobacterial persistence, and latent infection. In particular, novel therapeutic targets must be validated. We propose an innovative combination of cheminformatics, chemistry, and biology to find novel small molecule antituberculars, understand their effects on M. tuberculosis from both the pathway and biological target perspectives, and demonstrate their potential to seed new drug discovery strategies.

His research interests are:  The design and synthesis of chemical tools and their use in conjunction with biological methods to study infectious diseases (currently tuberculosis and malaria).


CANCELLED: Due to Inclement Weather

Tuesday, January 27th

Robert Best
National Institute for Health

TITLE: How well do all-atom folding simulations conform to the “funnel” picture of protein folding?

Cell fate determination is dependent upon the reliable integration of extracellular signaling cues into appropriate transcriptional outputs. When starved for nutrition, Saccharomyces cerevisiae can enter one of two differentiation pathways, meiosis or filamentous growth. Post-translational histone modifications are central to regulating the complex transcriptional programs that underlie cell fate decisions. Histones can be modified in a number of ways including acetylation, phosphorylation, ubiquitination, and methylation; dynamic and reversible combinations of these modifications allow communication between chromatin and the RNA pol II holoenzyme complex. While histone H3 Lys4 methylation is the best studied methyl mark, questions remain regarding how its regulation impacts cell fates.  In this talk, I will describe our genetic, molecular, biochemical and genomic results that detail how the CDK subcomplex of the RNA pol II holoenzyme interacts with the histone H3 Lys4 methylation regulators SET1 and JHD2 to guide cell fate decisions in yeast. 


Tuesday, January 20th

Dr. David Liberles
Department of Biology and Center for Computational Genetics and Genomics
Temple University

TITLE: Lineage-specific processes of genome diversification

Computational genomics is now generating very large volumes of data that have the potential to be used to address important questions in both basic biology and biomedicine. Addressing important biological questions becomes possible when mechanistic models rooted in biochemistry and evolutionary/population genetic processes are developed. Examples are described on problems involving the inference of duplicate gene retention mechanisms to apply in a gene tree/species tree reconciliation setting and towards understanding the role of gene duplication and deletion in cancer progression. Additionally, two classes of models for characterizing amino acid transitions during protein evolution are presented, one rooted in population genetics and the other rooted in protein physical chemistry. Ultimately, the development of such models adds to our tool box to enable inference of lineage-specific processes in comparative genomics.


Tuesday, November 18th

Catherine Guay
Doctoral Student, CCIB, Rutgers University–Camden



Tuesday, November 11th

Michael Law, PhD
Dept of Molecular Biology, School of Osteopathic Medicine
Rowan University

TITLE: Tipping the Balance: How CDK and histone methylation guide cell fate decisions

Cell fate determination is dependent upon the reliable integration of extracellular signaling cues into appropriate transcriptional outputs. When starved for nutrition, Saccharomyces cerevisiae can enter one of two differentiation pathways, meiosis or filamentous growth. Post-translational histone modifications are central to regulating the complex transcriptional programs that underlie cell fate decisions. Histones can be modified in a number of ways including acetylation, phosphorylation, ubiquitination, and methylation; dynamic and reversible combinations of these modifications allow communication between chromatin and the RNA pol II holoenzyme complex. While histone H3 Lys4 methylation is the best studied methyl mark, questions remain regarding how its regulation impacts cell fates.  In this talk, I will describe our genetic, molecular, biochemical and genomic results that detail how the CDK subcomplex of the RNA pol II holoenzyme interacts with the histone H3 Lys4 methylation regulators SET1 and JHD2 to guide cell fate decisions in yeast. 


Tuesday, October 28th

Dr Jinglin Fu
Assistant Professor, Rutgers–Camden 

TITLE: BioInspired Molecular Complexes on DNA nanoscaffolds

Living systems have evolved complex macromolecular nanostructure networks to mediate a range of cellular activities with high efficiency and specificity, including metabolic pathways, signaling transduction, gene expression and regulation. Many of these macromolecular systems are spatially organized with precisely controlled position and orientation of biomolecule components, which facilitate the functionality. Such examples include the substrate channeling in the multienzyme cascades and the light harvesting systems in photosynthesis. If these systems can be mimicked and constructed artificially, they could be applied to the realization of smart nanobioreactors and devices that have utility in the production of high-value chemicals, the conversion of a variety of energy forms, and the development of new bio-diagnostics. These studies will also increase our fundamental knowledge of biomolecule selfassembly and cellular metabolism in general. Recently, DNA has emerged as promising molecular scaffolds to organize macromolecule structures on the nanoscale with controlled geometries and nanomechanical capabilities. In this talk, I will present a DNA scaffold-directed strategy to assemble artificial biomolecular complex systems with precisely controlled spatial arrangements, and mimic biological functions for applications in catalysis, bioenergy and biomedicine.


Tuesday, October 21st

Rob Marmian
CCIB, Rutgers–Camden

TITLE: Space and time at the molecular level: Lessons from Wishful thinking


Tuesday, October 14th

Dr. Sean Smith
Post-Doctoral Researcher, CCIB, Rutgers – Camden

TITLE: Structural Variant Detection Using Whole Genome Sequencing

Structural variants are variations in chromosome structure that include deletions, insertions, duplications, inversions, and translocations.  Structural variants have been linked to several diseases including cancer.  This talk will describe how structural variants are detected using whole genome sequencing data and describe current work developing the structural variant detection algorithms GROM and GROM-RD.


Tuesday, October 7th

Dr. Sudha Moorthy
Scientist at PMC Advanced Technologies

TITLE: Vibrio cholerae: Lifestyle choices seen through the “genomics” lens


Tuesday, September 30th

Dr Laura Scheinfeldt
Research Scientist, Coriell Institute for Medical Research

TITLE: Using the Coriell Personalized Medicine Collaborative data to conduct a genome-wide association study of sleep duration

Sleep is critical to health and functionality, and several studies have investigated the inherited component of insomnia and other sleep disorders using genome-wide association study (GWAS) methodologies. However, genome-wide studies focused on sleep duration are less common. I will present sleep data from participants in the Coriell Personalized Medicine Collaborative (CPMC)(n=3948) together with demographic and lifestyle variables, and genome-wide SNP data to better understand genetic contributions to variation in sleep duration. I used stepwise ordered logistic regression with the following predictive variables: age, gender, weight, physical activity, physical activity at work, smoking status, alcohol consumption, ethnicity, and ancestry (as measured by principal components analysis). The strongest candidate loci replicated several genomic regions that were previously identified in GWAS related to sleep duration (TSHZ2, ABCC9, FBXO15) and narcolepsy (NFATC2 and SALL4). In addition, I have identified novel candidate genes for involvement in sleep duration including SORCS1 and ELOVL2. These results demonstrate that the self-reported data collected through the CPMC is robust, and even with a modest sample size, genome-wide association analysis has identified biologically interpretable genetic candidate genes involved in sleep duration. More generally, this study contributes to a better understanding of the complexity of human sleep variation.


Tuesday, September 23rd

Dr Percival Zhang
Biological Systems Engineering Department
Virginia Polytechnic Institute and State University

TITLE: Biotechnology Paradigm Shift: From Living Microorganisms to in vitro Synthetic Biosystems

The largest production challenge of biocommodities (e.g., biofuels, renewable chemicals, food, and feed) is the economically viable production with satisfying three manufacturing criteria: high product yield, easy product separation, and fast productivity. In vitro synthetic biosystems for biomanufacturing (ivSB2) are the implementation of complicated biological reactions via the in vitro assembly of numerous standardized and exchangeable enzymes or their complexes and/or (biomimetic) cofactors. Compared to microbial fermentation, ivSB2 features manufacturing advantages, such as high product yield, fast reaction rate, easy access and control for open systems, tolerance of toxic compounds and broad reaction conditions.

In this talk, I will introduce the concept of this disruptive technology platform, present its four major applications: (i) the highest yield production of hydrogen for C5 and C6 sugars; (ii) enzymatic transformation of cellulose to amylose, a value-added co-product, and (iii) the generation of electricity via a sugar biobattery; as well as develop building blocks — synthetic metabolons and engineered redox enzymes working on biomimetic cofatcors. In a word, ivSB2 could lead to a biotechnology paradigm shift, especially in the sustainability revolution pertaining to the energy-water-food nexus.


Tuesday, September 16th

Leonid Chindelevitch
Postdoctoral Fellow
Harvard School of Public Health

TITLE: Probing Networks to Understand Nature

Networks are a fundamental tool for understanding the intricate interconnections that govern biological systems. This talk will describe two ways in which networks, in combination with mathematical models and algorithmic techniques, can yield valuable biological insights. 

Causal regulatory networks help reveal the hidden regulators of gene expression patterns. To facilitate their analysis we established an efficient method for evaluating the significance of the overlap of ternary signals, which generalizes Fisher’s exact test. We used this method to analyze a large-scale causal regulatory network and uncovered new regulators of cardiac hypertrophy.

Metabolic networks help identify novel drug targets. We uncovered structural features of these networks that had been missed by previous researchers, and developed a theoretical framework based on duality for analyzing them in a consistent fashion. We used this theoretical framework to create a new metabolic network for Mycobacterium tuberculosis by algorithmically merging two existing networks, and identified several putative drug targets.

2013-2014 Seminars:

Wednesday, April 30th

Dr Mary Mullins

Cell and Developmental Biology
Perelman School of Medicine, University of Pennsylvania

TITLE: Dynamics and Shaping of a BMP Signaling Gradient

The vertebrate embryonic dorsoventral (DV) axis is patterned by a bone morphogenetic protein (BMP) activity gradient during blastula and gastrula stages.  This BMP morphogen gradient is shaped by BMP antagonists emanating from dorsal regions that block signaling dorsally and lead to a gradient of signaling with highest levels ventrally. Quantitation of this gradient, defining its range and the dynamics of its formation, as well as its modulation during gastrulation has not been investigated. We quantified in every cell of the embryo at 30-minute intervals the nuclear intensities of phosphorylated-Smad5 (P-Smad) protein, the BMP signal transducing protein. We use automated algorithms to identify the thousands of individual nuclei present at each embryonic time point, and to measure their corresponding P-Smad intensities. The quantitative dynamics of the gradient in blastula and gastrula stages will be presented, as well as the distinct roles of BMP antagonists in shaping this gradient.


Wednesday April 30th

Matthew Niepielko
CCIB Ph.D. Candidate


TITLE: Changes in BMP and EGFR signaling components underlie the evolution of Drosophila eggshell morphologies.

FIRST EVER CCIB Ph.D. Thesis Defense at Rutgers–Camden 


Thursday, April 17th

Tejashree Redij

TITLE: Studies on the biochemical and molecular mechanisms of thiourea mediated abiotic stress tolerance inBrassica juncea L.

Salinity and drought are the major abiotic stresses responsible for reducing the crop productivity and hence, worldwide research is focused to develop strategies for enhancing plant stress tolerance. In this context, the present study was initiated to evaluate the ameliorative potential of thiourea [TU; a non-physiological thiol based ROS scavenger] in Brassica juncea under salt and PEG stress. The entire study was performed on pot experiment. The concentration of 175mg/50g soil of NaCl, 1g/50g of soil of PEG (and 50mg/50g of soil thiourea was used throughout the experiment. The analyses were performed at two developmental stages viz. at seedling (1, 2 and 3 d after stress) and seed soaking (1 and 6 h after stress). In seedlings, thiourea supplementation along with NaCl or PEG stress was found to maintain the reduced redox state, which in turn favored the coordinated action of various enzymatic and non-enzymatic antioxidants and pro-oxidants to reduce the oxidative damage inside the plants. In seeds, thiourea supplementation differentially regulates the expression of a set of genes already known as markers of stress tolerance. The effect of thiourea was also found to be dependent upon ABA and calcium based signaling. Thus, the present study highlights the use of thiourea application as a technology for enhancing NaCl and PEG stress tolerance in Indian mustard.


Tuesday, April 15th

Kuhn Ip

TITLE: Mathematical Modeling of Bacterial Metabolism

The ubiquity of microbes in our lives has made research into microbial metabolism an important are of study. The biochemical reactions that comprise metabolism determine the consumption and production of chemical compounds and thus, directly relate to efficiency of microbial industrial fermentation. Metabolism and its regulation is also a key determinant in the virulence and survival of pathogenic microbes.

The key to engineering microbial metabolism for a particular purpose is finding targets for manipulation or modification to study experimentally. Microbial metabolism is complex and effects of modifications to a metabolic pathway are not necessarily localized and may be indirect. Trying to study metabolism as a whole entity by investigating all potential sets of modifications experimentally is infeasible. Thus, mathematical models combined with computational search algorithms have been used to ease the experimental burden by directing laboratory efforts towards promising candidates in a systematic and efficient fashion.

Constraint-based modelling, where metabolism is represented as a directed stoichiometric network of constrained biochemical reactions, is one such widely used framework for predicting metabolic phenotype.

Here, we present projects that consider two issues with the application of predictive modelling to metabolic engineering.

First, the complexity of genome-scale metabolic models affects our ability to interpret the predictions generated. A useful tool for understanding and manipulating cellular metabolism is decomposition into elementary flux modes, which systematically organize metabolic networks into potential pathways associated with biochemical functions. Its utility, however, is severely limited since the number of modes increases exponentially with the size of the network. We developed a new method for decomposition that can easily operate on genome-scale metabolic networks. We demonstrated the utility of our method for metabolic engineering of Escherichia coli and for understanding the survival of Mycobacterium tuberculosis during infection.

Second, the underlying model must successfully capture the effects of manipulations on the metabolic behavior of an organism. With constraint-based modelling techniques, it is not immediately clear how to model the correct behavior of inserted heterologous genes under artificial control. We developed a modelling method that we call Proportional Flux Forcing (PFF) to model artificially induced enzymatic genes within constraint-based modelling schemes. We applied PFF in conjunction with flux balance analysis-based computational strain optimization to yield non-obvious genetic manipulation strategies that significantly increase free fatty acid production in Escherichia coli with an artificially induced heterologous thioesterase.


Tuesday, April 15th

Martin Golubitsky
Mathematical Biosciences Institute
Ohio State University

Patterns of Synchrony: From Animal Gaits to Binocular Rivalry

This talk will discuss previous work on quadrupedal gaits and recent work on a generalized model for binocular rivalry proposed by Hugh Wilson. Both applications show how rigid phase-shift synchrony in periodic solutions of coupled systems of differential equations can help understand high level collective behavior in the nervous system.  For gaits the symmetries predict unexpected gaits and for binocular rivalry the symmetries predict unexpected percepts.


Elizabeth Demaray

Floraborgs, Victimless Leather: Work Samples From the Field of Art and Science Collaboration

Prof. Elizabeth Demaray manufactures alternative forms of housing for hermit crabs, cultures lichen on the sides of skyscrapers in New York City and, with the engineer Dr. Qingze Zou, is currently building the IndaPlant Project: An Act of Trans-Species Giving in which light-sensing robotic floraborgs allow houseplants to roam freely in a domestic environment, in search of sunlight. Demaray will present her work along with a brief overview of other artwork currently being made in the field of art and science collaboration. This emerging field of practice creates opportunities to heighten scientific literacy in the general public while illuminating the research of individual scientists. Demaray will additionally addresses the challenges and rewards inherent in soliciting institutional support, dealing with the media and presenting work in this genre of art making.


Tuesday, March 11th

Joanna Slusky

TITLE: The Ins and Outs of Membrane Proteins

Membrane proteins comprise 30% of all proteins and are the majority of modern drug targets. My talk will span both the inner and outer membrane and will use methodologies ranging from molecular biology to protein design to bioinformatics. I will discuss I) how charge affects membrane protein insertion and topology in the inner membrane, II) the relative forces responsible for membrane protein-protein interactions, and III) how charge location clarifies a mechanism for protein insertion in the outer membrane.


Monday, March 10th

Christopher C Govern
Postdoctoral Researcher
FOM Institute AMOLF Amsterdam, NL

TITLE: Fundamental limits on the precision of cellular sensing 

Cells can sense the concentrations of chemicals in their environments with remarkable precision, rivaling the sensory abilities of the best machines that humans build. Yet, they are built very differently than typical machines, with complex networks of molecular interactions and considerable noise in their outputs.  While much is known about sensory machines in general, we do not understand how cells actually build them out of molecular components or the design constraints cells face in doing so.  I first discuss how common signaling motifs affect the precision of cellular sensing, leading to the specific motifs that can achieve fundamental sensing limits.  I then consider design trade-offs that emerge between the performance of these networks and the resources required to build and operate them at the molecular level, like energy (fuel), copies of signaling proteins, and signal processing time.


Thursday, March 6th

Amin S. Ghabrial
Dept of Cell and Developmental Biology
University of Pennsylvania, School of Medicine

TITLE: “Tube morphogenesis”


Tuesday, March 4th

Buz Barstow

TITLE: Understanding the Bridge Between Renewable Electricity and Biological Metabolism

Electrosynthesis is a new approach to the production of renewable fuels and chemicals that combines the energy capture efficiency of renewable electricity with the metabolic versatility of biology. Naturally occurring electroactive microbes, that in the wild participate in the geochemical cycling of metals, provide the biological foundation for the uptake of renewable electricity into metabolism. However, despite recent advances, very few of these microorganisms, and others that offer unique capabilities to synthetic biology, can be easily genetically engineered and the systems biology of their unique behavior remains poorly understood. In this talk, I will describe the use of novel high-throughput genetic screens and sequencing methods to discover genes and molecular pathways that underly electron uptake in the model electroactive organism Shewanella oneidensis MR-1.


Thursday, February 27th

Vyacheslav Labunskyy

TITLE: New insights into translational regulation by the unfolded protein response and its role in aging revealed by ribosome profiling

Impaired protein function caused by protein misfolding and aggregation has been implicated in the development of age-related diseases and regulation of lifespan. Accumulation of misfolded proteins in the endoplasmic reticulum, a cellular organelle responsible for protein folding and trafficking, activates protective signaling pathways that restore protein homeostasis. One such conserved signaling pathway is mediated by the protein misfolding sensor Ire1p and the transcription factor Hac1p, which up-regulate endoplasmic reticulum chaperones, oxidative folding components and factors that facilitate degradation of misfolded proteins to alleviate increased protein folding demand. Here, we describe the role of the unfolded protein response (UPR) signaling pathway and its downstream targets in regulation of lifespan in yeast. While the loss of Ire1p itself had little effect on lifespan, we found that selective inactivation of the individual protein folding and maturation factors led to increased longevity. We also provide evidence that this increased longevity depends on functional Ire1p and is associated with constitutive activation of upstream UPR signaling. We applied RNA-seq and ribosome profiling coupled with next generation sequencing to elucidate the mechanism by which the UPR regulates longevity. Ribosome profiling is based on deep sequencing of ribosome-protected mRNA fragments and provides quantitative information on translation at the genome-wide level. Using this method, we performed detailed characterization of translational changes that are associated with increased UPR activity and identified a set of stress response factors up-regulated in the long-lived mutants. In addition to activation of known UPR targets, we observed induction of other cytoprotective pathways that result in resistance of cells to multiple stresses. These findings establish a novel role for UPR in multiple stress resistance and identify a signaling network that couples stress resistance to longevity.


Tuesday, February 25th

Dr. Orly Levitan
Environmental Biophysics and Molecular Ecology Program,
Institute of Marine and Coastal Sciences, Rutgers University, New Brunswick

TITLE: The Intelligent Design of Algal Biofuels

Although marine microalgae account for <1% of the photosynthetic biomass they account for > 45% of the global primary production. Over geological time scales, ca. 10-4 to 10-5 % of their organic carbon becomes incorporated into petroleum reservoirs. Each year, humans extract ~1 million years worth of accumulated oil, leading not only to an inevitable depletion of the reservoirs but to a massive increase in atmospheric CO2. Owing to their high productivity-to-biomass ratio, algae have been long considered as leading  candidates for biodiesel feedstock. Indeed, lipids derived from fossils of a specific algal taxon, the diatoms, are a major component of the highest quality petroleum. Diatoms are an extremely successful taxon in the contemporary oceans and accumulate triacylglycerols (TAG) as storage lipids. In the late 1990’s, genetic tools were developed for diatoms, and several fully sequenced genomes are now available in the public domain with more in the pipeline. These tools have enabled us to use diatoms as a platform for developing high lipid producing cells using a synthetic biological approach.

Using biochemistry, molecular biology, physiology, and biophysical tools, I took an integrative approach to understand the ‘carbon decision tree’ of the model diatom, Phaeodactylum tricornutum, and to denote several potential regulatory nodes that could alter its cellular carbon and energy allocation. Transcriptomic analysis revealed key pathways involved in the remodeling of intermediary metabolism of carbon and nitrogen that allow for the increase in lipid production. I have used molecular and advances transformation tools, to generate several knock-down (RNAi approach) and over-expression plasmids and target some of the postulated regulatory nodes of the central carbon and nitrogen metabolic pathways. The results have led to new cell lines with increased lipid production. An integrative analysis of the transformants indicates that manipulation of the diatom’s cellular carbon flow could be achieved by modification of the nitrogen assimilation pathway, TAG biosynthesis, and by overexpression of specific transcription factors. To displace the total U.S. consumption of fossil fuels, algae must be grown at a scale that yields approximately 20 million barrels of oil per day. Based on my work, I propose that by using genetically engineered diatoms as a platform, it is possible to achieve annual lipid yields that will enable the production of economically viable and environmentally sustainable biofuels for the transportation sector of the economy.


Thursday, February 20th

Abid Saleem
TITLE: “Localization of Brain Bio-Iodine”


Scott Davis
TITLE: “Starflag”


Wednesday, February 19th

CCIB Qualifying Exam
Thesis Director: Dr Hao Zhu

Marlene Kim


Oxidative stress causes cell damage which can lead to a variety of neurodegenerative diseases. Reactive oxygen species (ROS) that cause oxidative stress can trigger the transcription of antioxidative enzymes found in the antioxidant response element (ARE) signaling pathway. This pathway is essential for alleviating cell injury, but the mechanisms that lead to cytotoxicity and animal toxicity are still unclear. Previously, a cell-based ARE beta-lactamase reporter gene assay was used to screen over 2,800 compounds from the National Toxicology Program (NTP) and Environmental Protection Agency (EPA) libraries in a Quantitative High Throughput Screening (qHTS) format in efforts to evaluate environmental chemicals that activate the ARE pathway. These compounds were identified and used to develop predictive ARE models using Quantitative Structure-Activity Relationship (QSAR) approaches. The resulting models can be used to virtually screen other compounds of interest (e.g. Tox21 chemical library). Unfortunately, most QSAR models cannot be used to predict animal toxicity. Therefore, we hope to improve the current QSAR models by incorporating more biological information, especially in vitro information, to solve this problem. The integration of chemical and biological information will be used to develop Quantitative Structure In Vitro-In Vivo Relationship (QSIIR) approaches. The in vitro and in vivo relationships established in this step could be used to develop predictive models for complicated animal toxicity endpoints (e.g. neurotoxicity). Furthermore, the final alternative computational toxicity predictors could be used to prioritize potentially toxic compounds, that induce the ARE pathway, for experimental animal tests.


Thursday, February 13th

Joanna Slusky

TITLE: The Ins and Outs of Membrane Proteins

Membrane proteins comprise 30% of all proteins and are the majority of modern drug targets. My talk will span both the inner and outer membrane and will use methodologies ranging from molecular biology to protein design to bioinformatics. I will discuss I) how charge affects membrane protein insertion and topology in the inner membrane, II) the relative forces responsible for membrane protein-protein interactions, and III) how charge location clarifies a mechanism for protein insertion in the outer membrane.


Tuesday, February 11th

Dr. Kevin Chen
BioMaPS Institute for Quantitative Biology
Department of Genetics, Rutgers University, NB

TITLE: Spectral Learning of Hidden Markov Models for Genomic Segmentation

Since 93% of disease-related variants in the human genome reside outside of protein coding genes, it is important to develop computational techniques to predict which of these variants are most likely to be causal for the disease. Our group mainly uses computational techniques to interpret variation in the genome that affects the function of non-coding RNAs and gene regulatory elements. In this talk, I will describe our recent results on extending and implementing a novel class of spectral learning algorithms for Hidden Markov Models and related graphical models, with the goal of segmenting the genome into distinct chromatin.


Thursday, February 6th

Ruchi Lohia

TITLE: Prediction of the effects of the Val66Met polymorphism on the conformational ensemble of an intrinsically disordered protein, Brain-Derived Neurotrophic Factor

The discovery of Intrinsically Disordered Proteins (IDP) has challenged the structure-function paradigm and forced us to find new ways for identifying functional mechanisms of proteins. Studies show that IDPs can function while being partly disordered or may fold once they bind to their receptors. Disease-associated Single Nucleotide Polymorphisms (SNP) are common in the disordered regions of proteins, but not much is known about their effect on the protein structure. Brain Derived Neurotrophic Factor (BDNF) belongs to the family of neurotrophins, and facilitates neurogenesis in its short (mature) form but apoptosis in its long (pro) form. A common (found in 4% of the United States population) SNP that results in the Val66Met mutation in the disordered N terminus domain of the long form of BDNF (proBDNF) has been associated with various neuropsychiatric disorders such as bipolar disorder and Parkinson’s and Alzheimer’s diseases. In order to explore the effect of this SNP on protein structure and dynamics, we conducted Molecular dynamics simulations to identify the effect of the above SNP on likely conformations of proBDNF. Although IDPs have been identified to change their conformations rapidly, many also exhibit some residual secondary structure, which might be biased towards the bound conformation. To construct the ensemble of proBDNF in both forms, large-scale fully atomistic replica exchange calculations of both the Val and Met forms of proBDNF were carried out. We find significant differences in the secondary structure available to Val and Met forms of the protein in the region surrounding the SNP, with results that agree with recent NMR studies. This suggests a position specific residue-type dependence of the residual secondary structure of proBDNF, which might account for functional compromise.


Tuesday, February 4th

Dr. Darius Balciunas
Department of Biology, Temple University

TITLE: Conditional gene traps for genetic analysis of regeneration in zebrafish

Regeneration is one of the most fascinating and biomedically relevant biological processes. Studies implicating classical developmental pathways- Wnt, Fgf, Bmp and retinoic acid- in regeneration underscore the overlap between genetic control of development and regeneration, necessitating the use of conditional mutants to study regeneration. However, conditional mutants are only readily generated in the mouse, which has rather poor regenerative capacity. Conversely, in vertebrate model systems with extensive regenerative capacity, such as the zebrafish, very few conditional mutants exist. To address this chiasmus in regeneration biology, we have constructed a fully conditional gene trap vector for use in zebrafish. Several mutants affecting development of the cardiovascular system have been recovered from our pilot screens, including an insertional allele of tbx5a. Our data indicate that in addition to playing an essential role in pectoral fin and heart development, tbx5a plays an essential role in cardiac regeneration. Our future studies will focus on thorough characterization of regeneration defect in tbx5a mutants, while also testing regenerative capacity of other conditional cardiovascular mutants.


Thursday, January 30th

Kyle Jenkins

TITLE: Biomusicology: An Interdisciplinary Look at the Crossroads of Science and Art


Tuesday, January 28th

Zhijun Li, Ph.D. 

TITLE: Three-dimensional Structure Modeling of Transmembrane Proteins

Transmembrane proteins account for 30% of the human genome and are important drug targets. Elucidating the three-dimensional structures of membrane proteins is crucial to understanding their structure-function relationships and to their structure-based drug design. In disparity to their biological significance, the structure of most membrane proteins remains unknown, comprising less than 1% of the total structures in the Protein Data Bank. This is mainly due to the challenge of experimental structure determination of membrane proteins. As a result, computational modeling plays an important role in the studies of membrane proteins and in structure-based drug design efforts targeting these proteins.

In this talk, three ongoing projects from our lab that is related to structure modeling of helical membrane proteins will be presented: (1) Developing an objective measure for quality assessment of membrane protein structures/models through bioinformatics approaches; (2) Developing a computational approach for conformational sampling to improve the standard homology modeling techniques; and (3) Applying computational modeling techniques to the chemoreceptors and their regulatory enzyme. 


Thursday, January 23rd

Rachel Sohn

TITLE: Memory Reconsolidation as a Treatment Option for Opioid Dependency

Drug dependency, specifically to opioids, is a detrimental disease which has no known cure at the current time. Research has shown that abnormalities within the mesolimbic pathway in the brain can account for the negative behaviors associated with users. Posttraumatic stress disorder is another malady that is affected by the mesolimbic pathway, specifically to anomalies in the amygdala. By further researching this pathway, more conclusions can be drawn and pharmacological ways of treating the disease can be developed. Recent studies have focused on memory reconsolidation, a process of recalling memories and altering them. Using propranolol and clonidine, patients with PTSD showed great improvement in their quality of life as well as displayed minimal symptoms. Although not yet proven, this technique could be applied to those who are opioid dependent as a way to eliminate the triggering memories that cause a patient to relapse.


Thursday, November 7th, 2013

Dr. Bing Yan
School of Chemistry and Chemical Engineering
Shangdong University, China

TITLE: Modulation of the Biological Activities of Nanoparticles


Nanomaterials are widely used in various industrial sectors, biomedicine, and more than 1300 consumer products. Although there is still no unified safety regulation, their potential toxicity is a major concern worldwide. We discovered that nanoparticles target and enter human cells, perturb cellular signaling pathways, affect various cell functions, and cause malfunctions in animals. Because the majority of atoms in nanoparticles are on the surface, chemistry modification on their surface may change its biological properties significantly. We modified nanoparticle surface using a nano-combinatorial chemistry approach. Novel nanoparticles were discovered to possess reduced toxicity, enhanced cancer targeting ability, or increased cell differentiation regulation. Quantitative nanostructure-activity relationships (QNAR) models have been built and applied for predicting biocompatible nanoparticles.


Thursday, October 31st, 2013

Sulbha Choudhari
Center for Computational & Integrative Biology, Rutgers University-Camden

TITLE: Insights into Glacial Ecosystem using Metagenomics

The temperature in the Arctic region has been increasing in the recent past accompanied by melting of its glaciers. We took a snapshot of the current microbial inhabitation of an Alaskan glacier (which can be considered as one of the simplest possible ecosystems) by using metagenomic sequencing of 16S rRNA recovered from ice/snow samples. Somewhat contrary to our expectations and earlier estimates, a rich and diverse microbial population of more than 2,500 species was revealed including several species of Archaea that has been identified for the first time in the glaciers of the Northern hemisphere. The most prominent bacterial groups found were Proteobacteria, Bacteroidetes, and Firmicutes. Firmicutes were not reported in large numbers in a previously studied Alpine glacier but were dominant in an Antarctic subglacial lake. Principal component analysis of nucleotide word frequency revealed distinct sequence clusters for different taxonomic groups in the Alaskan glacier community and separate clusters for the glacial communities from other regions of the world. Comparative analysis of the community composition and bacterial diversity present in the Byron glacier in Alaska with other environments showed larger overlap with an arctic soil than with a high arctic lake, indicating patterns of community exchange and suggesting that these bacteria may play an important role in soil development during glacial retreat.


Tuesday, October 29th, 2013

William J. Welsh, Ph.D.
N. H. Edelman Professor in Bioinformatics
Department of Pharmacology, Rutgers University
Robert Wood Johnson Medical School

TITLE: Computational Approaches to Accelerate Drug Discovery

The recent emergence of the translational medicine paradigm has imposed a high premium on advanced computational platforms to accelerate the discovery of new diagnostic and therapeutic agents. We thus introduce two computational tools, Shape Signatures and Avalanche, developed in the Welsh laboratory that offer a central portal for drug discovery, virtual screening of chemical libraries, and predictive toxicology. Among their many attractive features, Shape Signatures and Avalanche are extremely fast, are accessible via a user-friendly GUI, and can handle any number and type of molecular species. Our current Shape Signatures and Avalanche chemical databases comprise over 3 million commercially available organic compounds including natural products and FDA-approved small molecule drugs. I will present Case Studies, taken from my research laboratory, to demonstrate the utility of Shape Signatures and Avalanche within an integrated drug discovery project. Examples will be drawn from projects aimed at the discovery of novel treatments for cancer, pain, and infectious, as well as cosmetic agents.


Thursday, October 24th, 2013

Dr. Wei Xu
Department of Oncology

McArdle Laboratory for Cancer Research, University of Wisconsin

TITLE: Developing in vitro and in vivo models for probing environmental estrogens’ action via estrogen receptor dimers

Many environmental estrogens so called xenoestrogens mimic the action of endogenous estrogens to regulate the risk of breast cancer. The effects of xenoestrogens are mediated by functional estrogen receptor dimers. Although numerous biochemical evidence exist in support of ERa/b heterodimer formation, the functions of heterodimers were completely unknown.

We have developed Bioluminescence Resonance Energy Transfer (BRET) assay to study intermolecular interactions of ERa/b heterodimers. Further, this assay was used for high throughput screening and identified several ERa/b heterodimer inducing compounds.

These compounds allow us to reveal the growth inhibitory function of ERa/b heterodimers and in silico modeling identifies possible pharmacophore conferring ERa/b selectivity. Finally, I will discuss recent animal models developed to screen ligands specific to ERa and ERb in vivo.


Thursday, October 17, 2013

Ammar Naqvi
Rutgers University-Camden

TITLE: Patterns of microRNA changes in Aging and Neurodegeneration

microRNAs (miRNAs) are 20~24nt small RNAs that impact a variety of biological processes, from development to age-associated events. To study the role of miRNAs in aging, studies have profiled the levels of miRNAs with time. However, evidence suggests that miRNAs show heterogeneity in length and sequences in different biological contexts. Here, by examining the expression pattern of miRNAs by northern blot analysis, we found that Drosophila miRNAs show distinct isoform pattern changes with age. Surprisingly, an increase of some miRNAs reflects increased 2′-O-methylation of select isoforms. Small RNA deep-sequencing revealed a global increase of miRNAs loaded into Ago2, but not into Ago1, with age. In addition, only specific miRNA isoforms showed increased loading into Ago2, but not Ago1, indicating a mechanism for differential loading of miRNAs between Ago1 and Ago2 with age. Mutations in Hen1 and Ago2, which lack 2′-O-methylation of miRNAs, result in accelerated neurodegeneration and shorter lifespan, suggesting an impact of the age-associated increase of 2′-O-methylation of small RNAs on age-associated processes. Our study highlights that miRNA 2′-O-methylation at the 3’end is modulated by differential partitioning of miRNAs between Ago1 and Ago2 with age, and that this process might impact age-associated processes in Drosophila.


Thursday, October 10th, 2013

Dr. Paolo Zunino
Department of Mechanical Engineering and Materials Science
University of Pittsburgh

TITLE: Computational models for fluid and chemical exchange between microcirculation and tissue interstitium

Reduced models of fluid flow or mass transport in heterogeneous media are often adopted in the computational approach when the geometrical configuration of the system at hand is too complex. A paradigmatic example in this respect is blood flow through a network of capillaries surrounded by a porous interstitium. We numerically address this biological system by a computational model based on the Immersed Boundary Method (IBM), a technique originally proposed for the solution of complex fluid-structure interaction problems. Exploiting the large aspect ratio of the system, we avoid resolving the complex 3D geometry of the submerged vessels by representing them with a 1D geometrical description of their centerline and the resulting network [1,2].

Cancer employs mass transport as a fundamental mechanism of coordination and communication and the physics of mass transport within body compartments and across biological barriers differentiates cancer from healthy tissues [3]. Mass transport is also at the basis of cancer pharmacological treatment Delivery of diagnostic and therapeutic agents differs dramatically between tumor and normal tissues. In contrast to healthy tissue, tumors exhibit interstitial hypertension, which is caused by the high permeability of tumor vessels in combination with the lack of functional lymphatic vessels in the tumor interstitial space.

The analysis of fluid and chemicals exchange in vascularized tumors is a relevant application of the model proposed here. We will use it to study fluid and mass exchange between the capillaries and the interstitial volume, as well as to compare different modalities to deliver chemotherapy drugs to the tumor mass, including using nanoparticles as delivery vectors.

[1] D’Angelo, C., Quarteroni, A. On the coupling of 1D and 3D diffusion-reaction equations. Application to tissue perfusion problems (2008) Mathematical Models and Methods in Applied Sciences, 18 (8), pp. 1481-1504.
[2] L.Cattaneo, P.Zunino, Computational models for fluid exchange between microcirculation and tissue interstitium. Networks and Heterogeneous Media (2013). MOX Report 25/2013
[3] Baxter, L.T., Jain, R.K. Transport of fluid and macromolecules in tumors. I. Role of interstitial pressure and convection (1989) Microvascular Research, 37 (1), pp. 77-104. 


Thursday, September 26th, 2013

Dr. Laura Scheinfeldt
Coriell Institute for Medical Research
Coriell Personalized Medicine Collaborative

TITLE: An integrated genomic approach to the study of human adaptation to high altitude

The recent availability of genomic data and related methodologies has resulted in several genome-wide studies of human adaptation across geographically diverse populations. Such studies have provided novel candidate genes and pathways putatively involved in adaptation to different environments, and in particular, to high altitude. However, one of the limitations of these studies is the high false positive rate for candidate loci, and additional work is needed to translate the strongest results into biologically interpretable adaptive candidate variants. I will discuss methods that may help to recover biological signals of adaptation to high altitude in Ethiopia and ways in which I have incorporated complementary phenotypic data. I will also present results from studies of other high altitude regions across the world and discuss the combined findings.


Tuesday, September 24th, 2013

Dr. Eric Klein
Dept. of Biology
Rutgers University-Camden

TITLE: Mechanical signaling pathways in bacteria

The dynamic regulation of virulence is an essential aspect of pathogenesis that holds great promise for combating infectious disease.  While the overwhelming emphasis of the field to date has been on the chemical cues that mediate bacteria-host interactions, there is evidence indicating that bacteria can also sense and respond to their mechanical environment.  In particular, I have demonstrated that uropathogenic Escherichia coli (UPEC) induce a novel gene expression program in response to adhesion to stiff surfaces.  While the mechanism by which fimbriae attach to their targets is well understood, little is known about how fimbrial attachment may trigger pathogenic gene expression.  Using a variety of genetic and microscopy-based approaches, my work will focus on how mechanical forces stimulate adhesion-mediated gene expression, the mechanism of bacterial mechanotransduction, and the role of mechanical signaling in pathogenic infection.  Ultimately, my goal is to identify components of the mechanotransduction pathway as targets for the development of novel therapeutics for use as alternatives to traditional antibiotics.


Thursday, September 19th, 2013

Dr. Luca Larini
Dept. of Physics, Rutgers University-Camden

TITLE: Bridging length and time scales in complex materials

Complex systems (such as biomolecules or glasses) are characterized by multiple time and length scales that are associated with different properties of the system under examination. As a consequence, simplified models (referred to as coarse-grained models) can be constructed that retain only the most relevant physical properties at a given scale. These models can be expected to render both theory and simulations more tractable. In this talk I will present examples of successful coarse-grained models and techniques applied to glass transition, biomolecules and simple liquids. These examples will be used to introduce basic notions of the theory and the algorithms employed in multiscale modeling.


Tuesday, September 17th, 2013

Dr. Jinglin Fu
Dept. of Chemistry, Rutgers University-Camden 

TITLE: Spatially Interactive Biomolecular Networks Organized by Nucleic Acid Nanostructures

The cellular activities of all organisms are governed by a variety of multi-step chemical conversion events, or biochemical pathways that exhibit extraordinary yield and specificity. Biological systems have evolved numerous mechanisms to regulate this process including molecular scaffolding and spatial confinement, where the function of a pathway is critically dependent on the relative position, orientation, and quantity of participating enzymes. Understanding the effect of spatial arrangement on pathway activity in multi-enzyme systems will not only advance our knowledge of fundamental biomolecule networks, but is also important to translate biochemical reaction pathways to non-cellular environment applications. Toward this goal, DNA nanostructures, that pieces of DNA can come together and spontaneously assemble into sophisticated structures, have been employed as assembly scaffolds to organize multiple enzymes with precisely-controlled spatial positions and orientation. This makes it possible to investigate and mimic several important mechanisms for multi-enzyme pathways, including the dependence of the distance between the enzymes on the overall reaction rate and specificity

(Fig.1A), the ‘Swing Arm’-organized substrate channeling (Fig.1B) and the regulatory enzymatic circuitry (Fig.1C). These approaches and principles provide a predictable framework to create efficient and regulatory nanoscale catalytic complexes, which will find utility in the development of the catalysts for chemical synthesis, bioenergy, diagnostic and therapeutic applications. 

2012-2013 Seminars:

Thursday, January 24, 2013, Science Building Lecture Hall
Extracting Essential Features of Biological Signaling Networks
Speaker: Dr Natalie Arkus, Postdoctoral Fellow, Department of Physics and Astronomy, University of Pennsylvania

Abstract: Because biological signaling networks have many components, it has become common to model such networks using large systems of coupled ordinary differential equations.  However, there is as yet no simple way of determining how solutions to large systems depend on their parameters.  In contrast, large systems of differential equations describing electronic circuits are routinely reduced to simpler systems that quantitatively capture circuit behavior using lumped parameters for resistance, capacitance, and inductance.  We show that biological signaling networks can similarly be reduced to systems involving a few equations and effective parameters.  The effective parameters lump the system’s many components together, yielding a simplified system that contains within it information on all of the many components.  We apply this method to a model from the literature of heat shock response in E. coli consisting of 31 equations and 48 parameters.  We reduce this model to just 1 equation and 3 effective parameters. The reduced system quantitatively agrees with the original, and demonstrates that feedback loops do not necessarily confer a faster heat shock response at lower cost, as had been claimed.  We discuss the application of this method to other models from recent literature, such as that of Beta-catenin degradation in the Wnt signaling network – where a model of 19 equations is reduced to 1-3 equations (depending on the initial conditions), and the features that determine the rate of beta-catenin degradation are extracted.

Tuesday, January 29, 2013, Armitage Hall Faculty Lounge
A Control Theory Approach to Engineering Biomolecular Networks
Speaker: Dr Domitillo del Vecchio, W. M. Keck Career Development Professor in Biomedical Engineering, Associate Professor, Laboratory for Information and Decision Systems (LIDS), Department of Mechanical Engineering, MIT

Abstract: The past decade has seen tremendous advances in the fields of Systems and Synthetic Biology to the point that de novo creation of simple biomolecular networks, or “circuits”, in living organisms to control their behavior has become a reality. A near future is envisioned in which re-engineered bacteria will turn waste into energy and kill cancer cells in ill patients. To meet this vision, one key challenge must be tackled, namely designing biomolecular networks that can realize substantially more complex functionalities than those currently available.

A promising approach to analyzing or designing complex networks is to modularly connect simple components whose behavior can be isolated from that of the surrounding modules. The assumption underlying this approach is that the behavior of a component does not change upon interconnection. This is often taken for granted in fields such as electrical engineering, in which insulating amplifiers enforce modular behavior by suppressing impedance effects. This triggers the fundamental question of whether a modular approach is viable in biomolecular circuits. Here, we address this research question and illustrate how, just as in many mechanical, hydraulic, and electrical systems, impedance-like effects are found in biomolecular systems. These effects, which we call retroactivity, dramatically alter the behavior of a component upon interconnection. We illustrate how, similarly to what is performed in electrical networks, one can reduce the description of an arbitrarily complex system by calculating equivalent retroactivities to the input. By merging disturbance rejection and singular perturbation techniques, we provide an approach that exploits the structure of biomolecular networks to design insulating amplifiers, which buffer systems from retroactivity effects. We provide experimental demonstration of our theory on a reconstituted protein modification cycle extracted from bacterial signal transduction and on a synthetic biology circuit in vivo.

Thursday, February 14, 2013, Science Building Lecture Hall
The Tox21 Program
Speaker: Menghang Xia, Ph.D., Group Leader, Cellular Toxicity & Signaling, NIH Chemical Genomics Center

Abstract: To meet the needs of toxicity testing in the 21st century, the National Toxicology Program (NTP), the NIH Chemical Genomics Center (NCGC), the U.S. Environmental Protection Agency (EPA), and the U.S. Food and Drug Administration (FDA) formed the Tox21 partnership. The goals of Tox21 are to identify mechanisms of compound action at the cellular level, prioritize chemicals for further toxicological evaluation, and develop useful predictive models of in vivo biological response. In the presentation, I will describe the Tox21 program, qHTS-based compound testing and the various Tox21 screening assays that have been validated and screened at the NCGC.

Thursday, March 7, 2013, 12:20pm – 1:20pm, Lecture Hall, Science Building 
Patterning challenges for optional sex: the case of reproductive polyphenism in aphids 
Speaker: Dr Gregory Davis, Assistant Professor, Biology, Bryn Mawr College

Abstract: The pea aphid, Acyrthosiphon pisum, exhibits several environmentally cued, discrete, alternate phenotypes (polyphenisms) during its life cycle. In the case of the reproductive polyphenism, differences in day length determine whether mothers will produce daughters that reproduce either sexually by laying fertilized eggs (oviparous sexual reproduction), or asexually by allowing oocytes to complete embryogenesis within the mother without fertilization (viviparous parthenogenesis). Oocytes and embryos that are produced asexually develop more rapidly, are yolk-free, and much smaller than oocytes and embryos that are produced sexually. Perhaps most striking, the process of oocyte differentiation is truncated in the case of asexual/viviparous development, potentially precluding interactions between the oocyte and surrounding follicle cells that might take place during sexual/oviparous development. Given the important patterning roles that oocyte-follicle cell interactions play in Drosophila, these overt differences suggest that there may be underlying differences in the molecular mechanisms of pattern formation. We have found differences in the expression of torso-like, as well as activated MAP kinase, suggesting that there are important differences in the hemipteran version of the terminal patterning system between viviparous and oviparous development. Establishing such differences in the expression of patterning genes between these developmental modes is a first step toward understanding how a single genome manages to direct patterning events in such different embryological contexts.

Wednesday, March 27, 2013, Campus Center Multi-Purpose Room
Fast Algorithms for Brownian Dynamics Simulation with Hydrodynamic Interactions
Speaker: Dr Shidong Jiang, Associate Professor, Department of Mathematical Sciences, New Jersey Institute of Technology

Abstract: In the Brownian dynamics simulation with hydrodynamic interactions, the motion of the Brownian particles can be described via a stochastic differential equation (SDE). The change of the displacement vectors of Brownian particles in the popular Ermak-McCammon algorithm for Brownian dynamics simulation consists of two parts: a deterministic part which is proportional to the product of the Rotne-Prager-Yamakawa (RPY) tensor and the given external forces; and a hydrodynamically correlated random part whose covariance is proportional to the RPY tensor. For an arbitrary N-particle configuration, the computation cost of the classical algorithms for computing the deterministic part is quadratic in N; and the computational cost for generating random vectors with a specific covariance is cubic in N. These form the bottleneck for long term large-scale Brownian dynamic simulation.

In this talk, we will first present two fast multipole methods (FMM) for computing the deterministic part. We then discuss several methods of generating random vectors whose covariance matrix is proportional to the RPY tensor.  The performance of our algorithms will be illustrated via several numerical examples. The algorithms are expected to be useful for the study of diffusion limited reactions, polymer dynamics, protein folding, and particle coagulation.

This is joint work with Zhi Liang at NJIT, Zydrunas Gimbutas & Leslie Greengard at NYU, & Jingfang Huang at UNC at Chapel Hill.

Thursday, March 28, 2013, 12:20pm – 1:20pm, Lecture Hall, Science Building 
Mathematical Models for Cancer Treatments – The Role of the Vasculature and the Immune System in Optimal Protocols for Cancer Therapies 
(joint research with Urszula Ledzewicz, Southern Illinois University) 
Speaker: Dr Heinz Schättler, Dept. of Electrical and Systems Engineering, Washington University, St Louis

Abstract: A systematic study of cancer treatments requires that we take into account not only the tumor and its growth, but also its microenvironment which comprises the cancerous cells, (sensitive and resistant to the treatment), healthy cells, tumor vasculature, immune system and more. In this talk, I will discuss some mathematical models that include increasingly more complex aspects of the tumor microenvironment such as tumor heterogeneity, angiogenic signaling, and tumor immune system interactions. These models will be analyzed from a dynamical systems point of view in the context of the optimal control problem of designing treatment protocols. Using methods of geometric optimal control, syntheses of optimal solutions will be described for some of these models. As more and more aspects of the tumor microenvironment are taken into account, optimal solutions change from bang-bang solutions (which correlate with the standard medical practice of giving chemotherapeutic agents in maximum tolerated doses) to administration schedules that favor singular controls (which administer agents at specific time varying reduced dose rates). This raises the possibility of metronomic administrations of agents (at low concentrations over prolonged periods without any major interruptions), an alternative scheduling approach that has shown some success in pediatric cancers. The talk will also address some of the mathematical challenges that arise in the analysis of these generally highly nonlinear, multi-input control systems. 

2011 – 2012 Seminars:

Monday, December 12, 2011, (BSB 334
Characterization of ultradian rhythms in adult male rats through EEG analyses and in Neuorspora crassa through growth data analyses 
Speaker: Steve Moffett, Ph.D. candidate, CCIB, Rutgers University

Abstract: The brain gives rise to rhythms on different time scales, including circadian or ultradian. In humans, hormone secretion is known to follow an ultradian rhythm of approximately 90 minutes. To date, ultradian rhythms have not been well-characterized in rodents. Adult male rats were prepared with electrodes for electroencephalography (EEG) and in the neck musculature for electromyography. After recovery, the EEG signal was recorded for 48-hours in a 12/12 L/D cycle. Following data acquisition, a window fast-Fourier transform (FFT) of EEG data was computed for 30-second epochs. The percentages of total power in 1-4 Hz, 4-8 Hz, or 1-8 Hz frequency bands were separately plotted by epoch over the course of the study. An ultradian rhythm in percent total power was apparent in the plots for each of the frequency ranges. To quantitate the ultradian rhythm, trained observers independently determined the time of occurrence of local minima in the window FFT plot. The means of measurements of periods between minima for given observers ranged from 9.4 to 13.2 minutes. A similar study was conducted on the growth data of the model circadian organism Neurospora crassa.

February 6, 2012
Systematic Structural Mass Spectrometry: Probing Structures of Membrane Skeletons Using Chemical Crosslinking, Mass Spectrometry and Homology Modeling
Speaker: David W. Speicher, Ph.D., Casper Wistar Professor in Computational and Systems Biology
Director, Center for Systems and Computational Biology, The Wistar Institute

Abstract: Crystallographic and NMR techniques have produced high resolution structures of many protein domains, small proteins and some protein complexes. However, few high resolution structures exist for proteins or protein complexes larger than 100 kDa, and no high resolution structures exist for the majority of proteins expressed by the human genome. A strategy for systematically determining novel protein structures is to use homology modeling since one or more high resolution structures exist for most protein folds. However, major challenges include: distinguishing between multiple plausible models, improving accuracy of predicted models, and experimental validation of models. A few distance constraints from chemical crosslinks, particularly “zero-length” linkers, can effectively address all of these challenges, and recent advances in tandem mass spectrometry (MS/MS) have improved in-depth analysis of complex peptide mixtures. Despite these advances, chemical crosslinkers remain under-utilized because there are no effective software tools for identification of peptides crosslinked by zero-length crosslinkers. While analysis of small proteins and protein complexes can be performed through manual review of the MS/MS data, this approach is very time consuming and tedious for moderate-sized proteins and impractical for large proteins and protein complexes. To address this roadblock, we recently developed software and a multi-tiered MS/MS analysis strategy that eliminates subjective, tedious manual review of MS/MS data, identifies more crosslinks, increases the confidence of crosslink assignments, and enables analysis of much larger proteins and protein complexes. We are applying this strategy to the systematic analysis of spectrin and other protein complexes in the membrane skeleton, a two-dimensional network on the cytoplasmic face of the membrane that provides membrane flexibility and integrity in red cells as well as other cell types. A long term goal is the development of a comprehensive medium resolution structure for the entire red cell membrane skeleton.

March 19, 2012 
What I Saw When I Watched Some Evolution 
Speaker: Dr. Michael Desai, Assistant Professor, Department of Organismic and Evolutionary Biology, Harvard University

Abstract: Evolutionary adaptation proceeds by the accumulation of beneficial mutations. We often think of these beneficial mutations as being rare, and adaptation is then characterized by a sequence of “selective sweeps”: a beneficial mutation occurs, spreads through an entire population, then later another beneficial mutation occurs, and so on. This simple picture is the basis for much of our intuition about adaptive evolution, and underlies a number of practical techniques for analyzing sequence data. Yet many large and mostly asexual populations — including a wide variety of unicellular organisms and viruses — live in a very different world. In these populations, beneficial mutations are common, and frequently interfere or cooperate with one another as they all attempt to sweep simultaneously. This radically changes the way these populations adapt: rather than an orderly sequence of selective sweeps driven by single strongly beneficial mutations, evolution is a constant swarm of competing and interfering mutations. The fate of any individual mutation depends on how it interacts with this background of other variation; no single mutation drives adaptation by itself. I will describe a new experimental system developed to directly visualize some aspects of these dynamics, and describe the results of 1000 generations of experimental evolution of 600 budding yeast populations. We see intriguing signatures of complicated patterns of interference between mutations, as well as the unexpected spontaneous evolution of stable polymorphisms in some populations. I will describe some further experiments to show how this dynamics depends on factors such as population subdivision and patterns of epistasis. If time allows I will also describe new theoretical work which predicts how many beneficial mutations collectively lead to variation in fitness within the population, and how each mutation interacts with this variation to determine its ultimate fate.  

April 9, 2012 
Automated Annotation of Chemical Names in the Literature
Speaker: Jun Zhang, PhD, Post-doc with Hao Zhu, Assistant Professor, Chemistry, Rutgers-Camden

Abstract: A significant portion of the biomedical and chemical literature refers to small molecules. The accurate identification and annotation of compound name that are relevant to the topic of the given literature can establish links between scientific publications and various chemical and life science databases. Manual annotation is the preferred method for these works because well-trained indexers can understand the paper topics as well as recognize key terms. However, considering the hundreds of thousands of new papers published annually, an automatic annotation system with high precision and relevance can be a useful complement to manual annotation. An automated chemical name annotation system, MeSH Automated Annotations (MAA), was developed to annotate small molecule names in scientific abstracts with tunable accuracy. This system aims to reproduce the MeSH term annotations on biomedical and chemical literature that would be created by indexers. To reduce the false-positive annotations, MAA incorporated several filters to remove “incorrect” annotations caused by nonspecific, partial, and low relevance chemical names. Accurate chemical name annotation can help researchers not only identify important chemical names in abstracts, but also match unindexed and unstructured abstracts to chemical records. The current work is tested against MEDLINE, but the algorithm is not specific to this corpus and it is possible that the algorithm can be applied to papers from chemical physics, material, polymer and environmental science, as well as patents, biological assay descriptions and other textual data.  

Monday, April 23, 2012, 12:10 – 1:10 pm, BSB 117 
Modeling and simulations of single-stranded RNA viruses 
Speaker: Mustafa Burak Boz, Georgia Institute of Technology, Ph.D. Candidate in Physical Chemistry

Abstract: We investigate the assembly of Satellite Tobacco Mosaic Virus (STMV) using coarse-grained models. We use multi-level coarse-grained representations to decrease the computational expenses and adequately represent the different parts of the viral structure. The RNA coarse-grained model is generated from a proposed secondary structure [1]. The RNA model has one pseudo-atom (bead) per residue. The coarse-grained model for the capsid contains twenty triangular units, each of which also contains three flexible positively charged protein tails. The assembly process as well as the stability of the virus mainly depends on RNA-protein and protein-protein interactions. The protein tails are attracted to the RNA by electrostatic interactions while the capsid proteins are weakly attracted with each other by hydrophobic interactions. We model RNA-protein interactions with a Debye-HÃŒckel potential and protein-protein interaction with a Lennard-Jones potential. We vary values of these two interactions to find regions where the virus is stable and will self-assemble. Finally, we investigate the assembly of the virus using molecular dynamics. These simulations help us understand the individual roles of these two interactions on viral assembly. 

Ref: 1. Schroeder JS, Stone, WJ et.al. Biophysical Journal,101: p. 167-175, 2011  

Thursday, April 26, 2012, 12:30 – 1:30 pm, Science Bldg, Science Lecture Hall 
Investigating functional roles of circadian rhythms in Neurospora crassa employing mathematical modeling and experimental validations
Speaker: Christian Hong, PhD, Assistant Professor, The Department of Molecular & Cellular Physiology, University of Cincinnati

Abstract: Fundamental cellular processes that maintain most organisms’ health and survival include cell cycle, DNA damage response, and circadian rhythms. Cell cycle is equipped with multiple checkpoints for controlled growth, DNA rep-lication, and divisions. DNA damage response (DDR) mechanisms control cell fate by either repairing single or double strand breaks, or triggering apoptosis for programmed cell death when the damage is fatal. Last, but not least, is circadian rhythm that keeps track of time of a day, and plays a central role in most organ-isms for setting the sleep/wake cycle, feeding rhythms, and other daily activities. These distinct molecular mechanisms communicate with each other and create a complex bio-molecular network to optimize conditions for cells to grow and adapt to the surrounding environment. We explore functional roles of circadian rhythms in other cellular processes such as cell cycle employing mathematical modeling and experimental validations using a modeling organism Neurospora crassa.  

Monday, April 30, 2012, 12:10 – 1:10 pm 
Immune-based identification of drug resistance in  Mycobacterium tuberculosis: Shifting a paradigm or tilting at windmills? 
Speaker: Gregory P. Bisson, MD, MSCE, Assistant Professor of Medicine and Epidemiology, Division of Infectious Diseases, Senior Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine

Abstract: Nearly 2 billion people, one third of the World’s population, are at risk of active tuberculosis (TB) because they are latently infected with the causative agent Mycobacterium tuberculosis ( Mtb ) , and almost 2 million TB-related deaths occur annually. A major barrier to TB control is that detection of Mtb drug resistance requires collection of microbiological samples, which are not available in many cases of active disease and in all cases of latent infection. Treatment of latent  Mtb  infection, a necessary approach to global TB control efforts, cannot be properly targeted if drug resistance is suspected, which represents a major knowledge gap. A central tenet of microbiology and infectious diseases holds that identification of antibiotic resistance in human pathogens requires direct access to the organism. In this talk, the hypothesis that the host adaptive cellular immune system responds to changes in the proteome of pathogens that specifically occur as a result of genetic mutation(s) conferring drug resistance will be presented, using rpoB mutation and rifampicin resistance in  Mtb   as an example.  The host immune system is not expected to consistently and specifically recognize epitope differences conferred by SNPs in rpoB , but data from model organisms phylogenetically related to Mtb indicate that rpoB mutation activates dormant gene networks not expressed by wild-type strains. The possibility that Mtb strains share conserved, ancestral responses of competition interference will be considered in light of preliminary proteomics data, and the public health implications of the approach will be discussed 

Thursday, June 21, 2012, 1:00pm – 2:00pm, Campus Center – South BC Conference Room 
Information Session on Entrepreneurial Collaborations 
Speaker: CCIB member faculty in conjunction with several faculty members of the School of Business

Abstract: The CCIB, in conjunction with several faculty members of the School of Business, is sponsoring a one-hour session to address possible collaborations on entrepreneurial endeavors, start-ups, etc., as well as the potential for related graduate course offerings and seminars. All interested parties are welcome to attend. 
The format for the meeting would be an initial general conversation on programmatic collaborations. This will be followed by a series of 5-10 minute presentations on projects of CCIB researchers and discussions with the members of the Business School on potential entrepreneurial ventures related to the research. Please reply to Karen Taylor at kdt41@camden.rutgers.edu if you would like to make a research presentation at the meeting. RSVP is requested via email to karen if you plan to attend. Thank you. 

Monday, June 25, 2012 
The Defence Science and Technology Organisation (DSTO) is part of Australia’s Department of Defence and Australian Government’s lead agency charged with applying science and technology to protect and defend Australia and its national interests ( http://www.dsto.defence.gov.au ). 
Speaker: Dr Gulay Mann BSc (Hons), Ph.D., Research Advisor to Defence Science Institute, Principal Research Scientist, Human Protection & Performance Division, Defence Science and Technology Organisation, Australia.

Abstract: In January 2002, Dr Mann commenced work with CSIRO Division of Plant Industry at the Black Mountain laboratories in Canberra. Her research activities included: a) The application of molecular/genetic analyses to investigate the genes responsible for complex dough attributes; b) Processing of novel cereal grains for maximum health benefit; c) Genetic basis of wheat quality; d) Development of improved analytical methods for key wheat quality traits; and e) Development of a laboratory scale baking facility. She has written numerous papers and conference proceedings on dough rheology, wheat and end product quality.
Dr Mann joined DSTO’ss Human Protection and Performance Division in February 2006 as an S&T 7 (corresponding to Principal Research Scientist), as Capability Leader of Defence Nutrition and Food Technology. Dr Mann provided scientific leadership for DSTO’ss research programs in Nutrition & Dietetics and Food Science & Technology, and also supervised the management of the freeze dried meal production line. 
In March 2009, Dr Mann took up a career development position at the DSTO Headquarters as the Director Strategic Planning and Coordination in Science Strategy and Policy Branch. In this role, she involved in the strategic coordination and science planning across DSTO as well as providing policy advice on the defence science and technology capabilities needed to achieve Defence’s broad objectives and priorities.
Since September 2011, Dr Mann is developing an enabling research program in Synthetic Biology.