The Biological Physics seminar series is organized by Gyan Bhanot, Anirvan Sengupta, and Alexandre Morozov. The purpose of these meetings is to present latest research and to foster an exchange of ideas in quantitative biology and biophysics, and occasionally to discuss latest developments from the Biological Physics group. Our goal is to keep most presentations general enough to be accessible to anybody with a physics background.

Unless announced otherwise, the meetings will be held from 12.30pm to 1.30pm in Hill 260 (**note the change in venue**).

The talks usually last 50-55 mins, with 5-10 mins devoted to questions and discussion. Presenters have a choice of using either the overhead projector or the blackboard.

      Organizer: Gyan Bhanot
      email: gyanbhanot at gmail dot com

• Speaker: Chase Broedersz, Princeton University
• Title: Organizing the bacterial chromosome for division
• Time/place: Friday, 02/07/2014 12:30pm Hill 260
• Abstract: The organization of the bacterial chromosome is complicated by the requirement for replication and segregation. Partitioning proteins of the ParABS system mediate chromosomal segregation many bacteria. At its heart, this segregation machinery includes a large ParB-DNA complex consisting of roughly 1000 ParB proteins. The nature of interactions between DNA-bound ParB proteins, and how these determine the structural properties of the partitioning module remain unclear. A central question is whether ParB spreads along the DNA to form a filamentous protein-DNA complex with a 1D character, or rather assemble to form a 3D complex on the DNA. Furthermore, it is unclear how the presence of only one or even a few parS sites can lead to robust formation and localization of such a large protein-DNA complex. We developed a simple model for interacting proteins on DNA, and found that a combination of 1D spreading bonds and a 3D bridging bond between ParB proteins constitutes the minimal model for condensation of a 3D ParB-DNA complex. These combined interactions provide an effective surface tension that prevents fragmentation of the ParB-DNA complex. Thus, ParB spreads to form multiple 1D domains on the DNA, connected in 3D by bridging interactions to assemble into a 3D ParB-DNA condensate. Importantly, this model accounts for recent experiments on ParB-induced gene-silencing and the effect of a DNA "roadblock" on ParB localization. Furthermore, our model provides a simple mechanism to explain how a single parS site is both necessary and sufficient for the formation and localization of the ParB-DNA complex.

• Speaker: Professor Jean-Marc Victor, Laboratoire de Physique Theorique de la Matiere Condensee Universite Pierre et Marie Curie, Paris, France
• Title: In silico single-molecule manipulation of chromatin fibers with physics engines
• Time/place: Thursday, 02/13/2014 12:00pm Hill 260 (Note special date and time!)
• Abstract: We develop a new powerful method to reproduce in silico single-molecule manipulation experiments. We demonstrate that flexible polymers like DNA or chromatin fibres can be simulated using physics engines thanks to an original implementation of Langevin dynamics in the open source library called Open Dynamics Engine. We moreover implement a global thermostat which accelerates the simulation sampling by two orders of magnitude. We retrieve force-extension as well as rotation-extension diagrams of reference experimental studies. We also obtain plectoneme diffusion along the DNA molecule and multiplectoneme conformations sporadically, in agreement with quite recent experiments [van Loenhout MTJ, de Grunt MV, Dekker C (2012) Dynamics of dna supercoils. Science 338: 94-97] and theoretical predictions [Emanuel M, Lanzani G, Schiessel H (2013) Multiplectoneme phase of double-stranded dna under tension. Phys Rev E 88: 022706].

• Speaker: Ann Hermundstad, University of Pennsylvania
• Title: Natural scene statistics predict perceptual salience of visual textures
• Time/place: Friday, 03/14/2014 12:30pm Hill 260
• Abstract: The statistical regularities of natural signals provide insight into characteristics of early sensory processing (e.g. redundancy removal via spatiotemporal decorrelation in the early visual system). Can the matching between natural signal statistics and neural processing mechanisms be extended beyond the sensory periphery? Recent results revealed that human visual sensitivity to fourth-order spatial correlations, known to arise in cortex, is closely related to the structure of fourth-order spatial correlations in natural scenes. This finding leads us to propose the following organizing principle: the perceptual salience of local spatial correlations increases with the variance, or unpredictability, of the corresponding correlations over the ensemble of natural scenes. In this seminar, I will discuss recent work that tests this principle in the human visual system by measuring the cortically-determined perceptual salience of a mathematically well-defined set of textures (a set of synthetic images with complex but controlled statistical properties). We find a strikingly detailed quantitative match between the measured sensitivity values and those predicted by natural scene statistics. This work provides clues to the mechanisms that enable a detailed match between the statistics of sensory inputs and the allocation of neural resources in the central nervous system.

• Speaker: Armita Nourmohammad, Princeton University - POSTPONED
• Title: TBA
• Time/place: Friday, 03/28/2014 12:30pm Hill 260 - POSTPONED DUE TO VISA PROBLEMS
• Abstract: TBA

• Speaker: David Schwab, Princeton University
• Title: Simple models of multicellular computation
• Time/place: Friday, 04/18/2014 12:30pm Hill 260
• Abstract: Populations of cells exhibit a remarkable diversity of behaviors, from the reliable development of multicellular structures to complex coding in neural ensembles. Proper characterization of these phenomena requires an understanding of how dynamics at the single-cell level, when combined with intercellular signaling and environmental cues, give rise to the collective behaviors observed in populations. First, I will present results characterizing the universal signaling dynamics in individual cells of social amoebae, and discuss cell density-dependent transitions to collective, synchronized oscillations. I will then consider population coding in retinal ganglion cells and demonstrate how complex collective behavior robustly arises due to shared stimulus input.

• Speaker: Shashi Thutupalli, Princeton University
• Title: Not-so-random walks in biology: two tales of how and why bacteria get to where they do
• Time/place: Friday, 05/02/2014 12:30pm Hill 260
• Abstract: The ability of individuals and their collectives to position themselves in space and time is a key driver of ecology. Here, I will present two experiments of the spatiotemporal redistribution of bacteria and its consequences on their multicellularity and population dynamics. First, I will describe how the soil bacteria myxococcus xanthus regulate their motility, in response to starvation, and form multicellular aggregates. The modulation of the individual motility allows the cells to explore space and aggregate into patterns beyond what is allowed by simple random walk dynamics. Second, I describe a predator-prey (worm-bacteria) system in which immotile bacterial cells hitch-hike on predatory worms and disperse to extremely long ranges. This dispersal has surprising consequences for the spread and growth of the bacteria (prey) and in turn the dynamics of the worm (predator) population.

The Biological Physics seminar series is organized by Gyan Bhanot, Anirvan Sengupta, and Alexandre Morozov. The purpose of these meetings is to present latest research and to foster an exchange of ideas in quantitative biology and biophysics, and occasionally to discuss latest developments from the Biological Physics group. Our goal is to keep most presentations general enough to be accessible to anybody with a physics background.

Unless announced otherwise, the meetings will be held from 12.30pm to 1.30pm in Hill 260 (**note the change in venue**).

The talks usually last 50-55 mins, with 5-10 mins devoted to questions and discussion. Presenters have a choice of using either the overhead projector or the blackboard.

      Organizer: Gyan Bhanot
      email: gyanbhanot at gmail dot com

• Speaker: Prof. Marcelo O. Magnasco, Laboratory of Mathematical Physics, The Rockefeller University, New York, NY
• Title: Phase Transitions in Neural Firing
• Time/place: Friday, 10/25/2013 12:30pm Hill 260
• Abstract: TBA

• Speaker: Dima Krotov, Princeton University (hosted by Pavel Khromov)
• Title: Criticality in transcriptional networks
• Time/place: Friday, 11/01/2013 12:30pm Hill 260
• Abstract: A transcriptional network's state is characterized by expression levels of multiple genes. If we take several copies of the same network in a given state, these expression levels will vary slightly due to fluctuations. These fluctuations are not statistically independent because some transcription factors can regulate the expression of others. Can we use the pattern of correlations of these fluctuations to say something about the architecture of the underlying network? Is there anything special about real biological regulatory networks as opposed to hypothetical networks that one can theoretically design? I will discuss these questions using the gap gene network of the Drosophila embryo as a primary example. Analysis of the recent experiments on this network shows four well-pronounced features: strong correlations, hierarchy of time scales in the temporal evolution of expression levels, long range correlations in space, and non-gaussianities in the distribution of fluctuations. All these signatures are related in ways predicted by theory and suggest that the underlying transcriptional network is tuned to a critical surface in its phase diagram. I will conclude with speculations about a possible biological function of this tuning.

• Speaker: Prof. Ken Irvine, Waksman Institute of Microbiology, Rutgers University, Piscataway, NJ
• Title: Regulation of Hippo signaling by cytoskeletal tension
• Time/place: Friday, 11/22/2013 12:30pm Hill 260
• Abstract: TBA

• Speaker: Prof. Luke F. Czapla, Department of Chemistry and Department of Engineering Science and Physics, College of Staten Island CUNY
• Title: Statistical Mechanics on Multiple Length Scales With Enhanced Sampling Techniques
• Time/place: Friday, 12/06/2013 12:30pm Hill 260
• Abstract: Molecular simulation is an established tool in investigating complex systems. In this talk, I will demonstrate a number of techniques for solving problems on multiple scales. The first will be the Wang and Landau Monte Carlo algorithm for investigating a complex free energy surface along the landscape of mesoscale looped DNA conformations. Next, I will demonstrate the String Method with swarms of trajectories for a complex problem involving single-stranded DNA translocation through a biological nanopore. Finally, I will illustrate the use of simulated annealing and replica exchange Molecular Dynamics for investigating complex lipid mixtures with a new coarse-grained model. It is hoped that the combination of results from simulations on multiple scales along with complex mathematical models can give greater insight into some of the major scientific challenges surrounding these problems.

• Speaker: Dr. Roland Krause, University of Luxembourg, Luxembourg Centre for Systems Biomedicine
• Title: Pharmacogenomics for epilepsy
• Time/place: Wednesday (note special time!), 12/11/2013 12:30pm Hill 260
• Abstract: Epilepsies affect about 3% of the European population in their lifetime. Existing anti-convulsant drugs have strong side-effects and fail in about 30% of patients. EpiPGX is a pharmacogenomics project with the long term aim to identify suitable drug treatment based on the genomic mark-up. Within the EpiPGX project, clinicians across Europe collaborate to assemble a sample collection with a detailed clinical phenotype. We provide data management and statistical support to the project. Genotyping and sequencing of this collection will enable a variety of analysis across questions such as the specics of adverse drug reaction, late response to drugs or general failure of control. I will show our recent progress in the project and our challenges in data analysis that require novel algorithms to tie in the variety of molecular and clinical data.

• Speaker: Dr. Gustavo Stolovitzky, Functional Genomics and Systems Biology, IBM Computational Biology Center, IBM Research, Yorktown Hts., NY
• Title: Seeking The Wisdom Of The Crowds Through Challenge-Based Competitions In Biomedical Research
• Time/place: Friday, 12/13/2013 12:30pm Hill 260
• Abstract: To enhance the impact that rich biological datasets can have in increasing our understanding of biological systems we created the DREAM (Dialogue for Reverse Engineering Assessment and Methods) initiative. DREAM’s mission is to contribute to the solution of important problems in biomedical research by posing double-blind prediction challenges to the computational biology community. The blind nature of the challenge allows us to evaluate predictions in a rigorous framework thus avoiding the traps of self-assessment. The many predictions submitted by the community allow us to tap on the “wisdom of the crowds”, the observation that the aggregate prediction is often better than the best individual prediction. In this talk I will discuss several challenges organized in the context of the DREAM initiative, including the DREAM5 Gene Network Inference challenge, the Sage-DREAM breast cancer prognosis challenge, and the NCI-DREAM drug sensitivity prognosis challenge. In these challenges we leveraged the participation of more than 150 research teams to infer gene regulatory networks, prognosticate survival in breast cancer patients and predict the sensitivity of cancer cell lines to different therapeutic compounds.

The Biological Physics seminar series is organized by Alexandre Morozov, Anirvan Sengupta, and Gyan Bhanot. The purpose of these meetings is to present latest research and to foster an exchange of ideas in quantitative biology and biophysics, and occasionally to discuss latest developments from the Biological Physics group. Our goal is to keep most presentations general enough to be accessible to anybody with a physics background.

Unless announced otherwise, the meetings will be held from 12.30pm to 1.30pm in Hill 260 (**note the change in venue**).

The talks usually last 50-55 mins, with 5-10 mins devoted to questions and discussion. Presenters have a choice of using either the overhead projector or the blackboard.

      Organizer: Alexandre V. Morozov
      email: morozov at physics dot rutgers dot edu

• Speaker: Purushottam Dixit, Brookhaven National Laboratory
• Title: A maximum entropy approach to extrinsic noise
• Time/place: Friday, 03/15/2013 12:30pm Hill 260
• Abstract: There exists a large cell-to-cell variability in the copy number of proteins and mRNA molecules. This variability is conceptually understood as arising from a combination of intrinsic random statistical mechanical fluctuations and global variation in extrinsic factors (e.g. number of ribosomes, RNA polymerase, etc.). While a large body of literature exists on modeling intrinsic noise, there has been limited theoretical attention to extrinsic noise. We present a maximum entropy framework to separate the intrinsic and the extrinsic contributions to noisy gene expression. We express the experimentally accessible probability distribution of the copy numbers of biochemical species by accounting for possible variations various rate constants due to fluctuating global extrinsic factors. The joint distribution of rate constants and the chemical species is estimated by maximizing its entropy. We will work out, in detail, the case of a constitutively expressing gene. Our results show that extrinsic factors quantitatively and qualitatively affect the experimentally observed distribution. Specifically, we suggest that the cell-to-cell variation in extrinsic factors accounts for the wider that Poisson distribution of mRNA copy numbers. We successfully test our framework on a numerical simulation of a simple gene expression scheme that accounts for the variation in extrinsic factors. We also test our predictions on previous experiments in E. coli.

• Speaker: Benjamin B. Machta, Princeton University
• Title: Critical fluctuations in cellular membranes
• Time/place: Friday, 04/26/2013 12:30pm Hill 260
• Abstract: The plasma membrane is a two dimensional liquid composed of a diverse soup of lipids and embedded proteins. In addition to separating inside from outside, the plasma membrane contains much of the cell’s machinery for receiving and processing information. Recent experiments suggest that these membranes are tuned very close to a liquid-liquid miscibility critical point in the 2D Ising universality class. I will first review the evidence for this critical point and argue that it likely underlies much of the lateral heterogeneity seen in the membranes of intact cells. I will then discuss criticality’s implications for processes mediated by membrane bound proteins. Composition fluctuations mediate a critical Casimir force that acts between proteins, becoming long-ranged close to the critical point. These forces may indirectly regulate protein function by affecting their localization. In addition, a protein’s functional state could directly couple to the local membrane composition. Such a protein would be allosterically regulated by membrane perturbations that change the critical temperature or the area fractions of the two liquid phases. This type of regulation may be widespread in membrane bound receptors and ion channels.

• Speaker: Hernan G. Garcia, Princeton University
• Title: Dynamical design principles for developmental patterning in live Drosophila embryos
• Time/place: Friday, 05/03/2013 12:30pm Hill 260
• Abstract: In single-celled organisms, synthetic biology has delivered on the promise of programming and controlling biological circuits in much the same way as electronic circuits. Multicellular organisms, however, have stayed relatively untouched by these efforts. Technological limitations have kept us in the dark about many of the design principles of developmental patterns, a necessary first step towards the synthetic design of de novo developmental response. In this talk I present a new method to access developmental decisions in living fruit fly embryos at the single nucleus level. Using this method we can determine developmental input-output functions by measuring where, when and how fast nuclei express a gene in response to an input morphogen. I show that the standard picture of transcriptional decisions, stemming mostly from knowledge from single-celled organisms, is insufficient to explain the formation of sharp boundaries along the embryo and that novel regulatory strategies are invoked by the fly in order to amplify otherwise shallow boundaries. This work provides a framework to understand and control developmental response by identifying the different regulatory strategies employed by the fly in the generation of patterns of gene expression.

• Speaker: Jeffrey Chuang, Jackson Laboratory for Genomic Medicine
• Title: Integrating Chemical Footprinting Data into RNA Secondary Structure Prediction
• Time/place: Friday, 05/17/2013 12:30pm Hill 260
• Abstract: Chemical and enzymatic footprinting experiments, such as shape (selective 2'-hydroxyl acylation analyzed by primer extension), yield important information about RNA secondary structure. Indeed, since the hydroxyl is reactive at flexible (loop) regions, but unreactive at base-paired regions, shape yields quantitative data about which RNA nucleotides are base-paired. Recently, low error rates in secondary structure prediction have been reported for three RNAs of moderate size, by including base stacking pseudo-energy terms derived from shape data into the computation of minimum free energy secondary structure. Here, we describe a novel method, RNAsc (RNA soft constraints), which includes pseudo-energy terms for each nucleotide position, rather than only for base stacking positions. We prove that RNAsc is self-consistent, in the sense that the nucleotide-specific probabilities of being unpaired in the low energy Boltzmann ensemble always become more closely correlated with the input shape data after application of RNAsc. From this mathematical perspective, the secondary structure predicted by RNAsc should be 'correct', in as much as the shape data is 'correct'. We benchmark RNAsc against the previously mentioned method for eight RNAs, for which both shape data and native structures are known, to find the same accuracy in 7 out of 8 cases, and an improvement of 25% in one case. Furthermore, we present what appears to be the first direct comparison of shape data and in-line probing data, by comparing yeast asp-tRNA shape data from the literature with data from in-line probing experiments we have recently performed. With respect to several criteria, we find that shape data appear to be more robust than in-line probing data, at least in the case of asp-tRNA. I will also describe some recent work from our lab on ribosome footprinting and the use of RNA structure to interpret protein-RNA interactions.

The Biological Physics seminar series is organized by Alexandre Morozov, Anirvan Sengupta, and Gyan Bhanot. The purpose of these meetings is to present latest research and to foster an exchange of ideas in quantitative biology and biophysics, and occasionally to discuss latest developments from the Biological Physics group. Our goal is to keep most presentations general enough to be accessible to anybody with a physics background.

Unless announced otherwise, the meetings will be held from 12.30pm to 1.30pm in Hill 260 (**note the change in venue**).

The talks usually last 50-55 mins, with 5-10 mins devoted to questions and discussion. Presenters have a choice of using either the overhead projector or the blackboard.

      Organizer: Alexandre V. Morozov
      email: morozov at physics dot rutgers dot edu

• Speaker: Siobain Duffy, Rutgers University
• Title: Fast evolution in DNA viruses: causes and consequences
• Time/place: Friday, 10/12/2012 12:30pm Hill 260
• Abstract: Emerging viruses -- viruses that are host-shifting and infecting new hosts -- usually have either RNA or single-stranded DNA (ssDNA) genomes. Estimates of their rates of evolution are similar, but the mechanisms by which ssDNA generate variation at the same rate as fast-mutating RNA viruses are unclear. ssDNA viruses replicate with the low mutation rate DNA polymerases of their host cells, and recombination alone cannot explain how ssDNA viruses behave like RNA viruses. We present bioinformatic analyses that indicate that one way ssDNA viruses increase their mutation rate is toleration of high rates of spontaneous oxidation of their nucleotide bases, especially at cytosines. This biased substitution pattern calls into question whether our current phylogenetic models are optimal for reconstructing the history of some viruses, which may compromise molecular epidemiology during outbreaks.

The Biological Physics seminar series is organized by Alexandre Morozov, Anirvan Sengupta, and Gyan Bhanot. The purpose of these meetings is to present latest research and to foster an exchange of ideas in Quantitative Biology and Biophysics, and occasionally to discuss latest developments from the Biological Physics group. Our goal is to keep most presentations general enough to be accessible to anybody with a Physics background.

Unless announced otherwise, the meetings will be held from 12.30pm to 1.30pm in E287, Serin every other Friday.

The talks usually last ~50-55 mins, with ~5-10 mins devoted to questions and discussion. Presenters have a choice of using either the overhead projector or the blackboard.

      Organizer: Alexandre V. Morozov
      email: morozov at physics dot rutgers dot edu

• Speaker: Suckjoon Jun, Harvard University
• Title: Chromosome, Cell Cycle and Entropy (or: why I love E. coli)
• Time/place: **Monday**, 01/23/2012 1:30pm **Hill 260** (note the special time & place!)
• Abstract: Before an Escherichia coli cell divides to give two viable daughter cells, the constantly growing cell must replicate, topologically decatenate, and spatially segregate its genetic materials. These processes pose non-trivial, conceptual questions at the interface between physics and biology. In this talk, I will discuss the questions in two independent and yet related contexts. In the first part, I will focus on the spatial processes involving chromosomes, and present experimental and theoretical results to show that the bacterial chromosome behaves as a loaded entropic spring, strongly confined by a crowded environment inside the cell. The second part concerns temporal processes the cell must coordinate, and I will show that E. coli possess a very robust mechanism of growth. I will conclude with one of the long-standing questions in biology, which we physicists may view as a "causality" problem.

• Speaker: Eva-Maria Schoetz, Princeton University
• Title: Body sculpting: Collective phenomena in development, regeneration, and asexual reproduction
• Time/place: **Monday**, 02/13/2012 3:00pm **Hill 260** (note the special time & place!)
• Abstract: Embryogenesis and regeneration are among the most striking and beautiful phenomena in nature. For a physicist, this brings together many major themes—pattern formation, information processing, the mechanics of complex fluid-like materials—that are essential for our understanding of life more broadly. Connecting macroscopic observables which we can quantify to their microscopic origins is one of the major challenges toward an understanding of these complex processes. In my talk I will give two examples that try to make this connection. First, I will discuss how tissue surface tension is connected to the mechanical properties of the constituent cells, such as cortical tension and adhesion. I will directly compare theoretical predictions with experimental data using primarily zebrafish embryonic tissues as the experimental system. In the second part of my talk, I'll switch gears to discuss asexual reproduction in planarians. Asexual reproduction and the ability to regenerate are intrinsically connected, but despite this important link, little is known about asexual reproduction in planarians due to experimental challenges. I will discuss our current understanding of the asexual population dynamics based on a large-scale experiment in which we have been tracking >10,000 divisions over the course of ~3 years and up to 55 generations using a custom-built Scan-Add-Print database system. Statistical analysis of the reproduction dynamics reveals a reproductive memory whose molecular basis we have now begun to elucidate.

• Speaker: Wolfram Moebius, Harvard University
• Title: Using minimal physical models to understand nucleosome organization around transcription start sites
• Time/place: Friday, 04/27/2012 12.30pm E287, Serin
• Abstract: The organization of nucleosomes along eukaryotic genomes strongly influences which parts of the DNA are accessible for binding of regulatory proteins and thus is an important factor controlling gene expression. Although a large amount of experimental and theoretical work has aimed to understand nucleosome organization, it so far remains only partially understood. We focus on a salient feature of nucleosome organization revealed by many experiments, a nucleosome-free region close to transcription start sites flanked by a pronounced periodic pattern in average nucleosome density. Using a top-down approach we investigate which minimal physical model can quantitatively explain this pattern. We find that a gas of hard rods is sufficient to describe the data for S. cerevisiae when taking different boundary conditions on both sides of the nucleosome-free region into account. The simple hard rod model, however, cannot describe the combined data for twelve different yeast species in a biologically sensible way. By considering transient unwrapping of DNA from the histone core within nucleosomes we derive a unified model which overcomes this limitation. In both models, oscillations in nucleosome density are caused by repulsive interactions, an effect known as statistical positioning. However, recent experiments appear incompatible with statistical positioning and indicate important roles for chromatin remodelers. While the available data is not sufficient to reconstruct remodeling mechanisms, we consider a minimal extension of our unified model and discuss how it can rationalize these new experimental results.

The Biological Physics seminar series is organized by Alexandre Morozov, Anirvan Sengupta, and Gyan Bhanot. The purpose of these meetings is to present latest research and to foster an exchange of ideas in Quantitative Biology and Biophysics, and occasionally to discuss latest developments from the Biological Physics group. Our goal is to keep most presentations general enough to be accessible to anybody with a Physics background.

Unless announced otherwise, the meetings will be held from 12.30pm to 1.30pm in E287, Serin every other Friday.

The talks usually last ~50-55 mins, with ~5-10 mins devoted to questions and discussion. Presenters have a choice of using either the overhead projector or the blackboard.

      Organizer: Alexandre V. Morozov
      email: morozov at physics dot rutgers dot edu

• Speaker: Alberto Perez, SUNY at Stony Brook
• Title: DNA flexibility
• Time/place: Friday, 10/21/2011 12:30pm E287, Serin
• Abstract: DNA usually interacts with some protein in order to carry out its biological functionality. There are two main aspects involved in describing these interactions. The first one is the direct contacts a given protein can establish with DNA. The second one has to do with the ability of DNA to deform into a conformation that allows interaction with the protein. This last point has been called the indirect readout, and it depends on the DNA sequence specific flexibility. During this talk I will focus on how atomistic models of DNA can help understand DNA flexibility and applications derived from these models.

• Speaker: Jeremy Curuksu, NYU
• Title: DNA conformational flexibility studied by molecular dynamics simulations of induced hinges and supercoiled minicircles
• Time/place: Friday, 11/04/2011 12:30pm E287, Serin
• Abstract: Bending and torsional deformations of DNA are important for its biological functions including recognition by proteins, packaging, replication and transcription. Recently it was shown that in free, circular DNA of length 100 base pairs which is the bending regime of nucleosomal DNA in vivo, the combined effect of torsional and bending stress can cause local unusual conformations [1]. My talk presents the methods I have used to study DNA flexibility by molecular dynamics simulations, including free energy simulations of kink defects [2] and simulations of supercoiled minicircles (circular DNA, [3]). Base pair kinks are observed in overwound minicircles and base pair unwinding in underwound minicircles. In the characteristic shape of the kinked minicircles only two-thirds of the fragment strongly bends (360� including kinks at the apexes) and writhes (360�), while the remaining segment is close-to-straight. I discuss further influences of local unusual conformations on DNA minicircle characteristic shapes.

  [1] Du, Kotlyar, Vologodskii (2008) Nucleic Acids Res. 36: 1120-8.

  [2] Curuksu, Zacharias, Lavery, Zakrzewska (2009) Nucleic Acids Res. 37: 3766-7.

  [3] Curuksu, Zakrzewska, Lavery, Maddocks (in preparation).

• Speaker: Adel Dayarian, UCSB (KITP)
• Title: Learning about evolution from sequence data
• Time/place: Friday, 11/18/2011 12:30pm E287, Serin
• Abstract: Recent advances in sequencing and in laboratory evolution experiments have made it possible to obtain quantitative data on genetic diversity of populations and on the dynamics of evolution. This dynamics is shaped by the interplay between selection acting on beneficial and deleterious mutations and recombination which reshuffled genotypes. Mounting evidence suggests that natural populations harbor extensive fitness diversity, yet most of the currently available tools for analyzing polymorphism data are based on the neutral theory. Our aim is to develop methods to analyze genomic data for populations in the presence of the above-mentioned factors. We characterize different evolutionary regimes - Muller’s ratchet, mutation-recombination-selection balance and positive adaption rate – as a function of the parameters of the model. We revisit a number of quantities and observables considered in the nearly-neutral theory of evolution. In particular, we examine the coalescent structure in the presence of recombination and calculate quantities such as the distribution of the coalescent times along the genome and the distribution of haplotype block sizes.

The Biological Physics seminar series is organized by Alexandre Morozov, Anirvan Sengupta, and Gyan Bhanot. The purpose of these meetings is to present latest research and to foster an exchange of ideas in Quantitative Biology and Biophysics, and occasionally to discuss latest developments from the Biological Physics group. Our goal is to keep most presentations general enough to be accessible to anybody with a Physics background.

Unless announced otherwise, the meetings will be held from 12.30pm to 1.30pm in E287, Serin every other Friday, starting January 28th, 2011.

The talks usually last ~50-55 mins, with ~5-10 mins devoted to questions and discussion. Presenters have a choice of using either the overhead projector or the blackboard.

      Organizer: Alexandre V. Morozov
      email: morozov at physics dot rutgers dot edu

• Speaker: Alexei Tkachenko, Brookhaven National Laboratory
• Title: Nanoparticles with DNA-mediated interactions: from mess to order and complexity
• Time/place: Friday, 02/11/2011 12:30pm E287, Serin
• Abstract: By decorating colloids and nanoparticles with various biomolecules, one can introduce highly selective key-lock interactions between them. This leads to a new class of systems and problems in soft condensed matter physics. In my talk, I will review a number of theoretical possibilities and recent experimental achievements in this new field. In particular, I will discuss DNA-mediated self-assembly of nanostructures and nanoclusters. The specificity and tunability of the interactions result in a remarkable morphological diversity of in such systems. In some of the proposed schemes, DNA can be used to essentially "program" the self-assembly of a desired structure. The colloids with type-dependent interactions can also be used for experimental realization of one of the simplest self-replicating system. Its study may shed some light onto such important problems as prebiotic evolution and the origin of life.

• Speaker: Nicolas Clauvelin, Rutgers University
• Title: Effects of histone tails on local structure and global properties of chromatin
• Time/place: Friday, 02/25/2011 12:30pm E287, Serin
• Abstract: Communication between sequentially distant sites along DNA is important in gene regulation and expression. These long-range interactions require deformations of the DNA, such as its tight wrapping around nucleosomes in chromatin. Indeed, the observed communication between transcription factors bound to widely spaced sites along nucleosome-decorated DNA is markedly greater than that along free DNA. In order to gain insight into how nucleosomes and the constituent DNA and histone proteins contribute to these effects, we have developed a simple, structurally based model of chromatin and performed Monte Carlo simulations of nucleosome-decorated DNA chains. Our coarse-grained representation takes account of the local structure and deformability of histone-bound and free (linker) DNA and the electrostatic interactions of representative DNA and amino-acid atoms. The simulated probabilities of long-range contacts mirror the enhancement of gene expression detected in model biochemical systems. The structure-based model (see figure) makes it possible to relate specific changes in nucleosome structure to global properties of the fluctuating chromatin chains. Analysis of the inter-nucleosome interactions is helping to unravel the details of distant communication on DNA as well as develop a simpler coarse-grained model of chromatin applicable to the study of longer, biologically relevant fragments.

• Speaker: Jayanth Banavar, Pennsylvania State University
• Title: Geometry and Physics of Proteins
• Time/place: Friday, 04/08/2011 12:30pm E287, Serin
• Abstract: Globular proteins are a key component of the network of life. We show that the results accumulated over the years lead to a unified framework for understanding proteins. The framework predicts the existence of a fixed menu of folds determined by geometry, clarifies the role of the amino acid sequence in selecting the native-state structure from this menu, explains the propensity for amyloid formation, and reveals an astonishing simplicity underlying the protein problem.

The Biological Physics seminar series is organized by Alexandre Morozov, Anirvan Sengupta, and Gyan Bhanot. The purpose of these meetings is to present latest research and to foster an exchange of ideas in Quantitative Biology and Biophysics, and occasionally to discuss latest developments from the Biological Physics group. Our goal is to keep most presentations general enough to be accessible to anybody with a Physics background.

Unless announced otherwise, the meetings will be held from 12.30pm to 1.30pm in E287, Serin every other Friday, starting September 17th, 2010.

The talks usually last ~50-55 mins, with ~5-10 mins devoted to questions and discussion. Presenters have a choice of using either the overhead projector or the blackboard.

      Organizer: Alexandre V. Morozov
      email: morozov at physics dot rutgers dot edu

• Speaker: Arjun Raj, University of Pennsylvania
• Title: Nature, nurture or just dumb luck: from single molecules to cell fate
• Time/place: Friday, 10/01/2010 12:30pm E287, Serin
• Abstract: Gene expression, the biochemical process by which a cell's genetic code is read out to produce proteins, is a fundamentally stochastic process. One consequence is that even genetically identical populations of cells in homogenous environments can often display significant cell-to-cell variability in the numbers of mRNAs and proteins. This raises a couple of questions. Can cells exploit this randomness in the execution of the genetic code for their own benefit? Conversely, do cells reduce the impact of variability in order to produce reliable outcomes in other contexts? We have developed an method that allows for the detection of individual mRNA molecules in a host of organisms to help us answer these questions by providing us with very sensitive measures of gene expression in individual cells. In particular, we have explored the impact of variability in gene expression on the process of development by studying the gene regulatory network responsible for gut formation during early embryonic development in C. elegans. We found that the normal gut development pathway is remarkably robust, but this robustness can be destroyed by mutations to a single gene that result in wildly varying embryonic fates. We have shown that these different fates result from the variable expression of a key upstream regulator in the rewired mutant gut pathway. These results suggest that redundancy in developmental gene networks can serve to mask and buffer otherwise hidden sources of gene expression variability.

• Speaker: Chris Henley, Cornell University
• Title: "Modeling virus capsid assembly: a multiscale approach"
• Time/place: Friday, 10/15/2010 12:30pm E287, Serin
• Abstract: I present work on two aspects of virus assembly, both from the thesis of Dr. Steve Hicks. The common theme is the use of toy models in statistical physics which, however, can be connected to real viruses (in particular HIV). The first project was an irreversible growth model in which triangular units are accreted, and the question is what parameters permit the formation of a closed shell at all. The second project was to extract from molecular dynamics simulations a number of elastic constants to represent the real interactions of two protein domains in the CA protein (that forms the mature HIV capsid).

• Speaker: Tobias Reichenbach, Rockefeller University
• Title: A ratchet mechanism for low-frequency hearing in mammals
• Time/place: Friday, 10/29/2010 12:30pm E287, Serin
• Abstract: Humans can hear sound at frequencies from about 20 Hz to 20,000 Hz. The lower part of this enormous frequency range, however, suffices for most of speech and music: telecommunication employs a voice frequency range from approximately 300 Hz to 3,400 Hz, and a piano's keys are tuned from 27.5 Hz to 4,186 kHz. Sound detection is achieved in the inner ear, or cochlea, which spatially separates frequencies: high frequencies are detected at the organ's base, and lower frequencies at more apical positions. While a mechanism, termed critical-layer absorption, has been identified for spatial separation of the high frequencies above 4,000 Hz, it does not apply for lower frequencies; understanding of low-frequency selectivity is currently lacking. We discuss a recently proposed ratchet mechanism for spatial separation of low frequencies. The mechanism employs the synergistic interplay of two known active processes in the mechanoreceptive hair cells to implement unilateral amplification; it thereby represents a mechanical analogue of the operational amplifier from electrical engineering.

• Speaker: Weiqun Peng, George Washington University
• Title: Epigenomics: from statistical analysis to biology
• Time/place: Friday, 12/10/2010 12:30pm E287, Serin
• Abstract: Eukaryotic genomes are organized into chromatin, the structure of which plays critical role in transcriptional regulatory program and the determination and maintenance of cell identity. Chromatin structure and function is regulated by a myriad of post-translational modifications on histone tails of the nucleosomes, which constitutes a major component of epigenomic information. Thanks to the recent advances in the next generation sequencing technology, the genomic landscapes of modified histones in higher eukaryotes have become available using chromatin immunoprecipitation followed with high-throughput sequencing (ChIP-Seq). These landscapes, however, turn out to be rather noisy and diffuse. I will discuss methods for sensitive and efficient identification of signals and domain strucutures in the epigenomic landscape, and present biological examples of important and unique information about gene regulation and cell differentiation provided by epigenomics.

The Biological Physics seminar series is organized by Gyan Bhanot, Alexandre Morozov, and Anirvan Sengupta. The purpose of these meetings is to present latest research and to foster an exchange of ideas in Quantitative Biology and Biophysics, and occasionally to discuss latest developments from the Biological Physics group. Our goal is to keep most presentations general enough to be accessible to anybody with a Physics background.

Unless announced otherwise, the meetings will be held from 12.30pm to 1.30pm in E287, Serin every other Friday, starting January 29th, 2010.

The talks usually last ~50-55 mins, with ~5-10 mins devoted to questions and discussion. Presenters have a choice of using either the overhead projector or the blackboard.

      Organizer: Alexandre V. Morozov
      email: morozov at physics dot rutgers dot edu

• Speaker: Thierry Mora, Princeton University
• Title: Statistical physics modeling of the bacterial flagellar motor
• Time/place: Friday, 01/29/2010 12:30pm E287, Serin
• Abstract: Many bacteria like E. coli swim by virtue of small rotary motors that drive rotation of helical flagella. Each motor is powered by a transmembrane proton flux passing through the motor. This flux is converted into torque with near-perfect efficiency by a mechanism whose details remain largely unknown. First I will describe the important biophysical properties of the motor, as measured in experiments, including the recent observation of a stepping behaviour at low speeds. I will then present a simple physical model that allows us to explain most of these data, but also to make new predictions. In particular, I will show how steps can be interpreted as barrier-crossing events in a corrugated energy landscape. Then I will show how to use our model to calculate the effect of shot noise (due to the discrete nature of the energy source--the protons) on motor diffusivity, and thus propose experiments to measure the proton cooperativity in the torque generation process.

• Speaker: Sridhar Hannenhalli, University of Pennsylvania
• Title: Comparative genomics of gene transcription
• Time/place: Friday, 02/12/2010 12:30pm E287, Serin
• Abstract: Our lab focuses on computational approaches to investigating eukaryotic transcriptional regulation and its evolution.In this talk, we will discuss a few projects that specifically exploit evolutionary signatures to (1) better model the interactions between transcription factors and their cognate cis elements (2) investigating functional divergence among gene copies after duplication. (3) time permitting, investigating signatures of selection acting via transcription factor binding sites in the human genome.

• Speaker: Konstantin Zeldovich, UMass Medical School
• Title: Linking evolution, protein stability, and cell growth dynamics
• Time/place: Friday, 02/26/2010 12:30pm E287, Serin
• Abstract: Thermodynamics of protein folding puts significant constraints on the rates and modalities of protein evolution. We will present an overview of recent models of protein and organismic evolution, highlighting the interplay between thermodynamic effects of mutations, mutation rates and population dynamics. Descending from population down to organism level, we will discuss a new model that links protein stability, fitness, and biomass growth rate, and show how seemingly disparate quantities such as the distribution of protein stabilities and distribution of interdivision times can be quantitatively reproduced within a single framework.

• Speaker: Gurinder Singh "Mickey" Atwal, Cold Spring Harbor Laboratory
• Title: Statistical Physics of Population Genetics
• Time/place: Friday, 03/26/2010 12:30pm E287, Serin
• Abstract: NA

• Speaker: Claus Wilke, The University of Texas at Austin
• Title: Selection for accurate and efficient gene expression
• Time/place: Friday, 04/09/2010 12:30pm E287, Serin
• Abstract: All cellular life depends on accurate and efficient expression of genes. Widely diverged organisms, from bacteria to vertebrates, experience similar selection pressures related to protein biosynthesis. (These selection pressures are often referred to as "translational selection".) I will present evidence for widespread occurrence of two different types of translational selection. First, I will discuss selection for translational accuracy. Synonymous codons differ in their translational error rates. Thus, the accuracy with which a gene is translated can be influenced by the codon usage bias of the gene. I will present evidence that codon usage is site-specific, such that more sensitive sites are encoded with codons that have reduced error rate. Thus, translational accuracy is increased at sites at which translation errors would be particularly harmful. Second, I will discuss selection for efficient translation initiation. Experimental work in E. coli has shown that strong mRNA secondary structure can interfere with efficient translation initiation. Motivated by this finding, we carried out a computational assesment of mRNA stability near the translation initiation site in over 340 complete genomes. We found that mRNA stability is generally reduced near the start codon in all three kingdoms of life. In prokaryotes, the strength of the effect correlates positively with genome GC content and negatively with the optimal growing temperature of the organism.

• Speaker: Chang Chan, Institute for Advanced Study
• Title: Hunting for Genes in Autism
• Time/place: Friday, 04/23/2010 12:30pm E287, Serin
• Abstract: Autism is a common childhood neuro-developmental disorder affecting one in 150 children. It is characterized by impaired social interaction and communication, and by restricted interests and repetitive behavior. Autism is a complex disease exhibiting strong genetic liability with a 25 fold increased risk for individuals having affected first-degree relatives. Moreover, the concordance for autism is over 90% for monozygotic twins while it is only 5-10% for dizygotic twins. Advances in genetics show autism to have etiological heterogeneity with each genetic susceptibility locus accounting for a few percent of cases or having a small effect. We have identified novel genes associated with autism. Our approach is to use single nucleotide polymorphism (SNP) genotyping chips to look for candidate genes. The data set provided by Autism Genetic Resource Exchange (AGRE) is a collection of over 800 families who have two or more autistic children. This choice of collection is to enrich for inherited genes in autism. We computed copy number variations (CNVs) and looked for associations with autism. Among the four best candidate genes we found, NRXN1 and CNTNAP2 previously had been found associated with autism. Both of these are membrane bound proteins found in neurons and the synapse. The other two genes are novel for association with autism and are similarly, membrane bound proteins found in neurons.

The Biological Physics seminar series is organized by Gyan Bhanot, Alexandre Morozov, and Anirvan Sengupta. The purpose of these meetings is to present latest research and to foster an exchange of ideas in Quantitative Biology and Biophysics, and occasionally to discuss latest developments from the Biological Physics group. Our goal is to keep most presentations general enough to be accessible to anybody with a Physics background.

Unless announced otherwise, the meetings will be held from 12.30pm to 1.30pm in E287, Serin every other Friday, starting September 18th, 2009.

The talks usually last ~50-55 mins, with ~5-10 mins devoted to questions and discussion. Presenters have a choice of using either the overhead projector or the blackboard.

      Organizer: Alexandre V. Morozov
      email: morozov at physics dot rutgers dot edu

• Speaker: Aleksandra Walczak, Princeton University
• Title: "Learning design principles from noisy small gene regulatory networks"
• Time/place: Friday, 09/18/2009 12:30pm E287, Serin
• Abstract: The regulation of gene expression in cells is a stochastic many body process. An important source of complexity in the interactions between genes lies in the molecular details, which control the properties of small genetic networks. The relatively small number of protein molecules of a given type present in the cell and the nonlinear nature of chemical reactions results in complex behaviours which are hard to predict from first principles. I will discuss mathematical models and approximations which allow for analytical progress in studying noise on different levels of the regulatory system. I will show examples of how molecular noise can influence the cell's phenotype and together with information flow considerations lead to predict not only the connectivity but also the detailed biochemistry of a biological network. Lastly, I will discuss different approaches of how a stochastic molecular level description can be successfully expanded to larger regulatory systems.

• Speaker: Joshua W. Shaevitz, Princeton University
• Title: "Bacterial Cell Mechanics and Motility"
• Time/place: Friday, 10/16/2009 12:30pm E287, Serin
• Abstract: Bacteria use several different structures to generate cells with specific mechanical properties. These properties are used by cells to weather a large variety of environmental stresses and play an important role in how many bacteria move. I will discuss our recent measurements of the interplay between bacterial mechanics and motility. To perform these measurements, we have had to develop a number of new techniques that combine elements of single-molecule biophysics, optical and force microscopy to perform detailed measurements in live cells.

• Speaker: Vikas Nanda, Department of Biochemistry, UMDNJ
• Title: "Negative Design and Supermolecular Assembly of Collagen"
• Time/place: Friday, 11/06/2009 12:30pm E287, Serin
• Abstract: Computational design has been successfully applied to the creation of new folds, biosensors and enzymes. Despite the fact that collagen is highly abundant and plays a key role in numerous biological processes, fibrous proteins have received little attention as computational design targets. Collagens are composed of three polypeptide chains that wind into triple-helices. We used a discrete computational model to design heterotrimer forming collagen-like peptides. Stability and specificity of oligomerization were concurrently targeted using a combined positive and negative design approach. The sequences of three peptides, A, B and C were optimized to favor charge-pair interactions in an ABC heterotrimer, while disfavoring the twenty-six competing oliogmers (i.e. AAA, ABB, BCA, etc.). Peptides were synthesized and characterized for thermal stability and triple-helical structure by circular dichroism. The designs were partially successful, associating with A:2B and 2B:C stoichiometry, while not forming other competing states. An analysis of structural models and computed versus experimental stabilities help us understand the role of electrostatics in collagen folding and provide important insight into how the stability and specificity of subsequent designs can be improved.

• Speaker: Michael Desai, Princeton University
• Title: "Watching a few mutations so we can imagine the rest: the dynamics of adaptation in large asexual populations"
• Time/place: Friday, 11/13/2009 12:30pm E287, Serin
• Abstract: We often think of beneficial mutations as being rare, and of adaptation as a sequence of selected substitutions: a beneficial mutation occurs, spreads through a population in a selective sweep, 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, evolution is a constant swarm of competing and interfering mutations. I will explain a new experimental system developed to enable us 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 an unexpected suggestion of frequency dependent selection in several populations. I will then describe ongoing theoretical work to understand the patterns of genetic diversity we expect to see in these populations, with an eye towards interpreting sequence data from a wide range of adapting asexual populations.

• Speaker: Gurinder Singh "Mickey" Atwal, Cold Spring Harbor Laboratory
• Title: Statistical Physics of Population Genetics
• Time/place: Friday, 12/11/2009 12:30pm E287, Serin
• Abstract: NA

The Biological Physics seminar series is organized by Gyan Bhanot, Alexandre Morozov, and Anirvan Sengupta. The purpose of these meetings is to present latest research and to foster an exchange of ideas in Quantitative Biology and Biophysics, and occasionally to discuss latest developments from the Biological Physics group. Our goal is to keep most presentations general enough to be accessible to anybody with a Physics background.

Unless announced otherwise, the meetings will be held from 12.30pm to 1.30pm in E287, Serin every other Friday, starting January 30th, 2009.

The talks usually last for about 50 mins, with 10 mins devoted to questions and discussion. Presenters have a choice of using either the overhead projector or the blackboard.

      Organizer: Alexandre V. Morozov
      email: morozov at physics dot rutgers dot edu

• Speaker: Hanna Salman, Department of Physics & Astronomy, University of Pittsburgh
• Title: "Effects of Nutrients and Concentration on Bacterial Thermotaxis"
• Time/place: Friday, 01/30/2009 12:30pm E287, Serin
• Abstract: We have developed new methods to explore the response of E. coli to temperature changes. A strong correlation between the population density and the response to a temperature gradient is observed. Bacteria that are grown below a critical concentration, in batch-mode cultures, swim towards warm regions when subjected to a temperature gradient. Above that concentration, they swim towards colder regions. Our findings indicate that a secreted intercellular signal, glycine, mediates this switch through methylation of Tsr receptors. At high bacterial concentration, the switch is reinforced by an inversion of the Tar/Tsr expression ratio.

• Speaker: Eric Vanden-Eijnden, Courant Institute, NYU
• Title: "Transition Pathways of Rare Reactive Events in Complex Systems"
• Time/place: Friday, 02/13/2009 12:30pm E287, Serin
• Abstract: The dynamics of biomolecular systems is typically characterized by a wide range of time scales, complicating their study via computer simulations. Of particular difficulty are situations which involve rare reactive events such as conformation changes of macromolecules, nucleation events during first-order phase transitions, chemical reactions, or bistable behavior of genetic switc. The occurrence of these rare events is related to the presence of dynamical bottlenecks of energetic and/or entropic origin which effectively partition the configuration space of the system into metastable basins. The system spends most of its time fluctuating within these long-lived metastable states and only rarely makes transitions between them. The rare events then determine the long-time evolution of the system. In this talk, I will present a general theoretical framework termed transition path theory (TPT) for the description of rare reactive events and compare it to other approaches such as the classical transition state theory (TST) and the more recent transition path sampling (TPS). I will also show that TPT can used to design efficient numerical algorithms such as the string method for the identification of the pathway, free energy and rate of the rare events. Both the theory and the numerics will be illustrated via examples.

• Speaker: Peter C. Kahn, Department of Biochemistry & Microbiology, School of Environmental and Biological Sciences, Rutgers University
• Title: Stabilizing Cellulase: On the Role of Buried Charge in Protein Conformational Stability
• Time/place: Friday, 02/27/2009 12:30pm E287, Serin
• Abstract: The research described here proceeds on two levels: fundamental and practical. The fundamental question concerns the role of ionically charged groups in protein stability. Ionically charged groups are strongly hydrated; the free energy cost of removing their water of hydration is large, although in the case of biomolecules, we do not know what that exact cost is. Because of the difficulty of "dehydrating" a charge, it has been understood since the classic review of Kauzmann in 1959 that charged moieties would tend to be found on the outside of proteins, while the hydrophobic effect would tend to drive aliphatic and aromatic groups into the protein interior. However, we have shown that a much larger fraction of the charged atomic surface area of proteins is buried out of contact with the aqueous solvent than had previously been believed. This raises the possibility that replacement of buried charged amino acids by polar uncharged residues of similar structure would reduce the free energy penalty of burial, leading to more stable enzymes. The hypothesis has been tested and shown to be correct. The immediate practical aim is to use our understanding of charge effects on stability to engineer a thermally stable cellulase. The enzyme would then be useful in converting biomass to glucose, which could be either fermented to produce fuel or used as a feedstock in other processes, such as making plastics. Work on the cellulase is intended to address both the fundamental and practical questions.

• Speaker: Troy Shinbrot, Department of Biomedical Engineering, Rutgers University
• Title: Why decussate? - Topological constraints on 3D wiring (Troy Shinbrot & Wise Young)
• Time/place: Friday, 03/13/2009 12:30pm E287, Serin
• Abstract: Many vertebrate motor and sensory systems "decussate", or cross the midline to the opposite side of the body. The successful crossing of millions of axons during development requires a complex of tightly controlled regulatory processes. Since these processes have evolved in many distinct systems and organisms, it seems reasonable to presume that decussation confers a significant functional advantage - yet if this is so, the nature of this advantage is not understood. In this talk, we examine constraints imposed by topology on the ways that a three dimensional processor and environment can be wired together in a continuous, somatotopic, way. We show that as the number of wiring connections grows, decussated arrangements become overwhelmingly more robust against wiring errors than seemingly simpler same-sided wiring schemes. These results provide a predictive approach for understanding how 3D networks must be wired if they are to be robust, and therefore have implications both for future large-scale computational networks and for complex biomedical devices.

• Speaker: Gary D. Stormo, Department of Genetics, Washington University in St. Louis
• Title: Modeling DNA-protein interactions
• Time/place: Friday, 03/27/2009 12:30pm E287, Serin
• Abstract: Is there a useful "recognition code" that can be employed to predict binding affinities of novel proteins? For many years researchers have searched for a "recognition code" that would predict quantitative affinities of protein-DNA complexes based only on their sequences and the known structures of transcription factor families. Such codes are required to be probabilistic, and there are now extensive data sets from which one can build models. But so far the best models are only moderately successful. This talk will describe the state-of-the-art, the likely limitations, and potential avenues for improvements.

• Speaker: Alexander Vologodskii, Department of Chemistry, New York University
• Title: DNA Bending
• Time/place: Friday, 04/10/2009 12:30pm E287, Serin
• Abstract: To analyze various issues related with DNA bending we need a theoretical model which provides accurate description of the phenomenon. The great majority of DNA macroscopic conformational properties are well described by a simple model, the discrete wormlike chain. For some important problems, however, we need information about DNA bending with base pair resolution, so we need a more detailed model. Four major features of such detailed model are considered in the talk: 1) Sequence dependence of DNA bending rigidity; 2) Intrinsic bends in the double helix 3) Anisotropy of the bending; 4) Deviations of the bending potential from the simplest harmonic form. More attention will be paid to the last issue which is directly related to the formation of local disruptions, kinks and open base pairs, in strongly bent DNA segments.

• Speaker: Edo Kussell, Center for Genomics and Systems Biology, New York University
• Title: Sensing and selection in bacterial populations
• Time/place: Friday, 04/24/2009 12:30pm E287, Serin
• Abstract: The ability to sense changes in the environment allows bacteria to respond by altering their phenotype, or behavior, to adapt to new conditions. Alternatively, bacteria have the ability to spontaneously change their phenotype, without sensing. Such behavior is known as stochastic switching. By simply observing dividing bacteria, is it possible to tell whether the cells are sensing their environment? This talk presents a theory that can decouple the action of sensing from the action of natural selection using single-cell observation of bacteria.

• Speaker: Chandran R. Sabanayagam, Department of Physics, Delaware State University
• Title: Molecular motors studied by fluorescence correlation spectroscopy
• Time/place: Friday, 05/08/2009 12:30pm E287, Serin
• Abstract: Molecular motors are fundamental components of living systems, and they can be classified as either rotary motors (e.g., F1-ATPase) or linear (e.g., kinesin). This talk will focus on the bacteriophage T4 molecular motor involved packaging DNA into a preformed capsid. We have used single-molecule fluorescence spectroscopy to understand the DNA (substrate) requirements for efficient packaging: DNA bubbles, single-stranded regions, overhangs, nicks and gaps were explored. Our general results give evidence that the T4 viral motors acts to compress DNA, and the resulting stored potential energy is then used to drive the linear motion of DNA into the capsid.

• Speaker: Marek Cieplak, Institute of Physics, Polish Academy of Sciences
• Title: Coarse-grained models of biomolecules, virus capsids, and proteins with knots
• Time/place: Friday, 06/05/2009 12:30pm E287, Serin
• Abstract: The structure-based models of proteins are defined through the condition that their ground state coincides with the native state of the proteins. There are many variants of such models and they yield different properties. Optimal variants can be selected by making comparisons to experimental data on single-molecule stretching. Among the best variants turn out to correspond to: a) the Lennard-Jones potential in the native contacts with the uniform amplitudes and variable length parameters. This model is applied to several problems: 1) theoretical surveys of stretching properties of thousands of proteins of known native structure, 2) dynamics of proteins with knots, 3) unravelling of proteins by fluid flows, and 4) modelling of nano-indentation of virus capsids. It is then generalized to DNA and used to study stretching, shearing, and twisting of the DNA double helix.

The Biological Physics seminar series is organized by Gyan Bhanot, Alexandre Morozov, and Anirvan Sengupta. The purpose of these meetings is to present latest research and to foster an exchange of ideas in Quantitative Biology and Biophysics, and occasionally to discuss latest developments from the Biological Physics group. Our goal is to keep most presentations general enough to be accessible to anybody with a Physics background.

Unless announced otherwise, the meetings will be held from 12.30pm to 1.30pm in E287, Serin every other Friday, starting September 12th, 2008.

The talks usually last for about 50 mins, with the rest devoted to questions and discussion. Presenters have a choice of using either the projector or the blackboard.

      Organizer: Alexandre V. Morozov
      email: morozov at physics dot rutgers dot edu

• Speaker: David Talaga, Department of Chemistry and Chemical Biology, Rutgers University
• Title: "New methods and results for probing the conformational changes in the earliest stages of amyloid formation"
• Time/place: Friday, 09/12/2008 12:30pm E287, Serin
• Abstract: Alzheimer's Disease and Parkinson's Disease are two examples of a class of disorders marked by the accumulation of amyloid in the affected organ. The formation of plaques of amyloid fibrils is associated with the progression of these diseases. The Talaga group is investigating the earliest steps in the conversion of soluble proteins to amyloid fibrils with the goal of understanding and disrupting the "amyloid cascade" before it initiates. Toward this end the Talaga group has developed several new approaches to investigating amyloid formation and protein aggregation. These new approaches have provided new insights to the types of species present during amyloidogenic protein aggregation. These new approaches and the insights they have provided will be discussed.

• Speaker: Vijay Balasubramanian, Department of Physics, University of Pennsylvania
• Title: "Towards a theory of the structural and functional organization of the retina"
• Time/place: Friday, 09/19/2008 Note the special date! 12:30pm E287, Serin
• Abstract: The retina is a light-sensitive area of the central brain comprising ~65 types of cells and a complex web of microcircuitry. One hundred years of study since the work of Cajal have illuminated many details of the structural and functional organization of these circuits. I will argue that a theory of this organization can be developed by asking how information in natural scenes can be efficiently processed, subject to the metabolic, spatial, temporal and noise constraints inherent in biological computation. I will pay particular attention to metabolic constraints, and will describe our efforts to quantitatively measure the cost of communication in the optic nerve. The examples that I will discuss include: (a) the relative scarcity of Blue cones and the retina's indifference to Red/Green cone ratio, (b) the shape of individual retinal ganglion cell receptive fields, (c) the organization of these receptive fields into mosaics covering the visual space, (d) the separation into distinct cell types, each creating its own mosaic, and (e) the distribution of information traffic across the different channels in the optic nerve. Our analyses are based on a new, calibrated, high resolution database of chromatic images from a baboon habitat in the Okavango Delta, Botswana.

• Speaker: Sergei Maslov, Department of Condensed Matter Physics and Materials Science, Brookhaven National Laboratory, Upton, New York
• Title: "Equilibrium and dynamical properties of protein binding networks"
• Time/place: Friday, 10/10/2008 12:30pm E287, Serin
• Abstract: We study the Law of Mass Action equilibrium of the Protein-Protein Interaction (PPI) network in yeast using experimentally determined protein concentrations, localizations, and binding partners. In particular, we are interested in how this equilibrium responds to changes in copy numbers of individual proteins [1-3]. We show that the magnitude of shifts between the free (monomer) and bound (heterodimer) concentrations of perturbed proteins is mainly influenced by such factors as the topological structure of the network, concentrations of its protein nodes, and the average binding strength. Our primary conclusion is that on average the magnitude of the perturbation exponentially decays with the network distance away from the perturbed node. This explains why, despite a globally connected topology, individual functional modules in such networks are able to operate fairly independently. In a separate project [4] we quantify the interplay between specific and non-specific binding interactions under crowded conditions inside living cells. We show how the need to minimize the waste of resources to non-specific interactions limits the proteome diversity and the average concentration of co-expressed and co-localized proteins.

  [1] Propagation of large concentration changes in reversible protein binding networks, S Maslov, I. Ispolatov, Proc. Natl. Acad. Sci USA 104:13655-13660 (2007). arXiv:0708.2421.

  [2] Maslov, K. Sneppen, I. Ispolatov, New Journal of Physics 9: 273 (11 pages) (2007). arXiv:q-bio/0611026.

  [3] K-K. Yan, D. Walker, S. Maslo, Fluctuations in Mass-Action Equilibrium of Protein Binding Networks, (2008); Phys Rev. Lett. (submitted) arXiv:0803.1471.

  [4] J. Zhang, S. Maslov, and E. I. Shakhnovich, Constraints imposed by non-functional protein-protein interactions on gene expression and proteome size, Molecular Systems Biology, in press (2008).

• Speaker: Boris Reva, Memorial Sloan Kettering Cancer Center - Computational Biology Center
• Title: "Determinants of Protein Function Revealed by Combinatorial Entropy Optimization" (B.Reva, Y.Antipin, C.Sander)
• Time/place: Friday, 10/24/2008 12:30pm E287, Serin
• Abstract: We use a new algorithm (combinatorial entropy optimization, CEO) to identify specificity residues and functional subfamilies in sets of proteins related by evolution. Specificity residues are conserved in a subfamily, but differ between subfamilies, and typically encode functional diversity. We obtain good agreement between predicted specificity residues and experimentally known functional residues in protein interfaces. Such predicted functional determinants are useful for interpreting the functional consequences of mutations in natural evolution and disease.

• Speaker: Alexander E. Kister, The University of Medicine and Dentistry of New Jersey (UMDNJ)
• Title: "Supersecondary structures of proteins: folding patterns and sequence patterns"
• Time/place: Friday, 11/14/2008 12:30pm E287, Serin
• Abstract: To describe the supersecondary structure (SSS) of beta proteins, we introduced a SSS unit called the "strandon". Representing proteins as the assembly of strandons exposes the underlying similarities in their SSS and enables us to construct a novel structural classification scheme in the SSS database. Analysis of the SSS of sandwich-like proteins reveals two specific folding patterns, which describe the arrangement of strandons and strands in the almost all protein domains. In this work was shown that proteins from different families with very low sequence similarities but with an identical supersecondary structure (SSS) have a common sequence pattern. To find common sequence regularities a new algorithm of the multiple sequences alignment was developed. It follows from the results of this work that the protein sequence/structure relationship cuts both ways. That is both the sequence of amino acids determines the folding pattern, and the structure defines key positions in sequences and residues at these positions - sequence pattern.

• Speaker: Hanna Salman, Department of Physics & Astronomy, University of Pittsburgh
• Title: "Effects of Nutrients and Concentration on Bacterial Thermotaxis"
• Time/place: POSTPONED to 01/30/2009
• Abstract: We have developed new methods to explore the response of E. coli to temperature changes. A strong correlation between the population density and the response to a temperature gradient is observed. Bacteria that are grown below a critical concentration, in batch-mode cultures, swim towards warm regions when subjected to a temperature gradient. Above that concentration, they swim towards colder regions. Our findings indicate that a secreted intercellular signal, glycine, mediates this switch through methylation of Tsr receptors. At high bacterial concentration, the switch is reinforced by an inversion of the Tar/Tsr expression ratio.

• Speaker: Daibhid O'Maoileidigh, Max-Planck-Institut fur Physik Komplexer Systeme
• Title: "The active process of the mammalian inner ear"
• Time/place: Friday, 12/12/2008 12:30pm E287, Serin
• Abstract: Despite the passing of over 150 years since the discovery of the hearing organ the mechanism of hearing remains unknown. A nonlinear active process is thought to be responsible for the ear's large dynamic range, sensitivity, high frequency selectivity and ability to emit sound spontaneously. In particular, the mammalian inner ear contains sensory cells whose cell bodies are formed by the most piezoelectric material known and on whose apices reside active force generators. The role and relative importance of these cell properties has been the most hotly debated topic in the field of hearing research for the last 20 years. We present a physical description of cochlear mechanics by examining the interaction between these two key features of the sensory outer hair cell. The integrated system exhibits generic properties, resulting from the proximity of its operating point to a Hopf bifurcation, which account for the main characteristics of hearing.

The Biological Physics seminar series is organized by Gyan Bhanot, Alexandre Morozov, and Anirvan Sengupta. The purpose of these meetings is to present latest research and to foster an exchange of ideas in Quantitative Biology and Biophysics, and occasionally to discuss latest developments from the Biological Physics group. Our goal is to keep most presentations general enough to be accessible to everybody with a Physics background.

Unless noted otherwise, the meetings will be held from 12.30pm to 1.30pm in the Condensed Matter seminar room (W112, Serin - please note the room change!) every second Friday, starting on January 25th, 2008.

The talks will last for about 45-50 mins, with the rest devoted to questions and discussion. Presenters have a choice of using either the projector or the blackboard.

      Organizer: Alexandre V. Morozov
      email: morozov at physics dot rutgers dot edu

• Speaker: Eleni Katifori, Harvard University
• Title: Folding of pollen grains
• Time/place: Friday, 01/25/2008 12:30pm W112, Serin
• Abstract: At dehiscence, which occurs when the anther reaches maturity and opens, pollen grains dehydrate and their volume is reduced. The pollen wall deforms to accommodate the volume loss, and the deformation pathway depends on the initial turgid pollen grain geometry and the mechanical properties of the pollen wall. We demonstrate, using both experimental and theoretical approaches, that the design of the apertures (areas on the pollen wall where the stretching and the bending modulus are reduced) is critical for controlling the folding pattern, and ensures the pollen grain viability. An excellent fit to the experiments is obtained using a discretized version of the theory of thin elastic shells. Additionally, as a 2-D analogue of a dessicating pollen grain, we consider a hydrostatically pressurized ring and discuss how an arc-length dependent bending modulus would determine the ring deformation.

• Speaker: Kerwyn Huang, Princeton University
• Title: ORGANIZATION OF THE CELL WALL OF GRAM-NEGATIVE BACTERIA
• Time/place: Friday, 02/08/2008 12:30pm W112, Serin
• Abstract: Bacterial cells come in a wide variety of shapes and sizes, with the peptidoglycan cell wall as the primary stress-bearing structure that dictates cell shape. In recent years, cell shape has been shown to play a critical role in regulating many important biological functions including attachment, dispersal, motility, polar differentiation, predation, and cellular differentiation. Though many molecular details of the composition and assembly of the cell wall components are known, how the peptidoglycan network organizes to give the cell shape during normal growth, and how it reorganizes in response to damage or environmental forces have been relatively unexplored. We introduce a quantitative mechanical model of the bacterial cell wall that predicts the response of cell shape to peptidoglycan damage in the rod-shaped Gram-negative bacterium Escherichia coli. To test these predictions, we use time-lapse imaging experiments to show that damage often manifests as a bulge on the sidewall, coupled to large-scale bending of the cylindrical cell wall around the bulge. The direction of bending confirms the hypothesis of a longitudinal orientation of peptides and a circumferential orientation of glycan strands in the peptidogylcan layer. Our simulations based on our physical model also suggest a surprising robustness of cell shape to damage, allowing cells to grow and maintain their shape even under conditions that limit crosslinking. Finally, we show that many common bacterial cell shapes can be realized within the model via simple spatial patterning of peptidoglycan defects, suggesting that subtle patterning changes could underlie the great diversity of shapes observed in the bacterial kingdom.

• Speaker: Paul Francois, Rockefeller University
• Title: Deriving structure from computational evolution
• Time/place: Friday, 02/22/2008 12:20pm W112, Serin
• Abstract: In superior animals, segmentation is the patterning process that leads to the formation of body metameric units such as segments in insects or vertebrae in vertebrates. Computational evolution is used to explore evolutionary pathways leading to possible segmentation networks. When the evolution is guided by a generic fitness function that just counts the number of segment boundaries, we invariably observe a very constrained evolutionary path. Surprisingly, the system spontaneously evolves towards a genetic network that implements the phenomenological ``clock and wavefront'' model proposed by Cooke and Zeeman in 1976. Simulations therefore propose explicit genetic interactions that may be later checked experimentally. Our computation illustrates how complex traits can evolve by the incremental addition of new functions on top of preexisting traits.

• Speaker: Benjamin Greenbaum, Rutgers University
• Title: Patterns and Evolution in RNA Viral Genomes
• Time/place: Friday, 03/07/2008 12:20pm W112, Serin
• Abstract: Viruses are obligate parasites that co-opt their host's replication machinery for survival. As such, they can be used to probe properties of hosts as well as viruses. After an introduction to the many types of viruses, I will focus on some computational approaches to finding significant motifs in viruses with single-stranded RNA genomes. These viruses can replicate outside of the nucleus, a fact which can test some ideas about viral properties, such as the origin of CpG underrepresentation. The evolution of CpG dinucleotides is studied in further depth for Influenza A, where we posses a ninety year time series of genomes. We conclude by speculating on the host mechanisms behind this viral evolution.

• Speaker: Gasper Tkacik, Princeton University
• Title: Information flow and optimization in transcriptional regulation
• Time/place: Friday, 04/04/2008 12:20pm W112, Serin
• Abstract: In the simplest view of transcriptional regulation, the expression of a gene is turned on or off by the changes in the concentration of a transcription factor (TF). Here we analyze transcriptional regulatory elements with the tools of information theory. Recent data on noise levels in gene expression are used to show that it should be possible to transmit much more than just one regulatory bit. Realizing this optimal information capacity would require that the dynamic range of TF concentrations used by the cell, the input/output relation of the regulatory module, and the noise levels of binding and transcription satisfy certain matching relations. This parameter-free prediction is in good agreement with recent experiments on the Bicoid/Hunchback system in the early Drosophila embryo, and this system achieves around 90% of its theoretical maximum information transmission. The dependence of information capacity on parameters that govern gene expression for simple, single-input / single-output, genetic regulatory elements is systematically examined and the extensions of the work to genetic circuits consisting of several interacting elements are presented.

• Speaker: Jean Lehmann, Rockefeller University
• Title: On the degeneracy of the genetic code
• Time/place: Friday, 04/18/2008 12:20pm W112, Serin
• Abstract: In this talk, I will discuss the main constraints on the anticodon-codon interaction within the ribosome. A simple analysis shows that the stability of the base-pair at the second position of the anticodon determines the type of degeneracy allowed at the third position.

• Speaker: Kerri-Ann Norton, Rutgers University
• Title: A Mechanistic Model of DCIS Progression
• Time/place: Friday, 05/02/2008 12:20pm W112, Serin
• Abstract: We have developed a 2D in-silico model of the growth of DCIS in a single breast duct. Every time step in the simulations, cells can either divide or die. In silico cells are subjected to forces due to adhesion, intra-ductal pressure and thermal fluctuations, and are found to produce tumors of varying morphologies. The tumors grow as a single monolayer that fills the intra-ductal space as new cells are created. We study the effects of parameters: polarity, apoptosis, necrosis, intra-ductal pressure and proliferation, on the morphology and time course of tumor growth. Our simulation reproduces all morphologies known from in-vivo observations, each morphology emerging in a distinct parameter regime. We identify the boundaries between different morphological forms in the space of parameters, and we find that under conditions of high intra-ductal pressure, medium to low apoptosis and high proliferation, the model generates papillary tumors which progress to cribriform and develop a necrotic core after long times. On the other hand, a high apoptotic rate results in papillary tumors which never develop a necrotic core, whereas at high proliferation and low apoptotic rates, we see solid tumors which progress to the comedo form. At very high apoptotic rates, as long as the proliferation rate is not too high we find that the subtype stays papillary and does not progress into other subtypes over long periods of time. This indicates that different cancerous growth behaviors (represented by different initial parameters) may have different invasive potentials even though they have the same morphologies.

This is an informal discussion session organized by Gyan Bhanot, Alexandre Morozov, and Anirvan Sengupta. The purpose of these meetings is to discuss interesting papers in quantitative biology and biophysics, and to present latest results from the Biological Physics group. The presentations will be general enough to be accessible to everybody with a Physics background.

Unless noted otherwise, the meetings will be held from 12.30pm to 1.30pm in the Cond. Matt. Theory discussion room (E287, Serin) every second Friday, starting on September 21st, 2007.

The talks will last for about 30-35 mins, with the rest devoted to questions and discussion. Most talks will be blackboard (the room choice limits us to that as well) but occasionally one may have printed figures or a laptop going around the room.

      Organizer: Alexandre V. Morozov
      email: morozov at physics dot rutgers dot edu

• Speaker: Pankaj Mehta, Princeton University
• Title: Exponential sensitivity of noise-driven switching in genetic networks
• Time/place: Friday, 12/14/2007 12:30pm E287, Serin
• Abstract: Cells are known to utilize biochemical noise to probabilistically switch between distinct gene expression states. We demonstrate that such noise-driven switching is dominated by tails of probability distributions and is therefore exponentially sensitive to changes in physiological parameters such as transcription and translation rates. However, provided mRNA lifetimes are short, switching can still be accurately simulated using protein-only models of gene expression. Exponential sensitivity limits the robustness of noise-driven switching, suggesting cells may use other mechanisms in order to switch reliably.

• Speaker: Gyan Bhanot, Rutgers University
• Title: Boolean Networks: Can they be used to model states of cells? (Journal Club)
• Time/place: Friday, 11/16/2007 12:30pm E287, Serin
• Abstract and References: I will discuss the contents of a paper by Tang et al. [1] which describes a Boolean network model for the stability and robustness of the yeast cell cycle. Since this will be a chalk talk, the audience is encouraged to print the paper and bring it to the meeting (reading the paper in advance is also highly encouraged). Following this, I will propose some other problems that might benefit from similar modeling.
  1. "The yeast cell-cycle network is robustly designed" by Li et al, Proc.Nat.Acad.Sci. 101, 4781 (2004)

• Speaker: Justin Kinney, Princeton University
• Title: Fitting physical models of protein-DNA binding energy to sequence data
• Time/place: Friday, 11/02/2007 12:30pm E287, Serin
• Abstract: One of the defining characteristics of modern biology is the ease with which one can obtain massive amounts of DNA sequence information. I will discuss how such data, coupled with relatively crude functional measurements, can be used to infer precise physical models of protein-DNA interaction energy. The relationship between likelihood and mutual information plays a central role in this inference problem, and suggests a general way in which modern sequencing technology might be used to probe the complex physical interactions underlying the regulation of gene expression.

• Speaker: Swagatam Mukhopadhyay, Rutgers University
• Title: Stochasticity in Gene Expression - Part 1 (Journal Club)
• Time/place: Friday, 10/19/2007 12:30pm E287, Serin
• References:
  1. "Tunability and noise dependence in differentiation dynamics" by Elowitz et al, Science 315, 1716 (2007)
  2. "Stochastic gene expression in single cell" by Elowitz et al, Science 297, 1183 (2002)

• Speaker: Mohammad Sedighi, Rutgers University
• Title: Epigenetic Chromatin Silencing: Bi-stability and Front Propagation
• Time/place: Friday, 10/05/2007 12:30pm E287, Serin
• Abstract: A mean-field dynamical model of chromatin silencing in budding yeast is suggested and the conditions giving rise to two states: silenced and un-silenced, will be studied. Based on these conditions, the space of control parameters is divided into two distinct regions of mono-stable and bi-stable solutions. Then, considering both the discrete and continuous versions of the model, the formation of a stable boundary between the silenced and un-silenced areas on DNA is investigated. The dynamics of the boundary is also studied under different conditions. Consequently, assuming negative feedback due to possible depletion of silencing proteins, the model explains a paradoxical epigenetic behavior of yeast that happens under some mutation. A stochastic treatment of the model is also considered to verify the results of the mean-field approximation and also to understand the role of intrinsic noise at single cell level.

• Speakers: Gyan Bhanot, Alexandre V. Morozov, Anirvan Sengupta (Rutgers University)
• Title: Organizing session; overview of research interests of the members of the Biological Physics group
• Time/place: Friday, 09/21/2007 12:30pm E287, Serin
• Abstract: NA

Maintained by morozov at physics dot rutgers dot edu