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@physics.rutgers.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@physics.rutgers.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@physics.rutgers.edu