Guest Seminars
Upcoming Seminars
Workshop on Imaging for High Throughput Phenotyping
Oct. 1, 2009, 9 AM-5 PM Systems Biology Center, French Family
Science Center, Room 4233
The goal is to exchange information among Centers and with the local community on imaging with a focus on high throughput phenotyping. Limited space is available. Please contact Blythe Boquist to register.
Imaging platforms
9:00-9:30 Wolfgang Busch (Duke) "The RootArray"
9:30-10:00 Anjali Iyer-Pascuzzi (Duke) "Non-invasive root architecture imaging platforms"
10:00-10:30 White Group (Chicago) "Live imaging of Drosophila development"
Break 10:30-11:00
Image acquisition software
11:00-11:30 Quanli Wang (You & West group, Duke) "Single cell tracking"
11:30-12:00 Uwe Ohler (Duke) "Region of interest image acquisition"
12:00-12:30 Darren Tyson (Vanderbilt) "Live single cell imaging of human cancer cells"
Lunch 12:30-1:30
Image analysis software
1:30-2:00 Sorger group (Harvard) "ImageRail"
2:00-2:30 John Harer (Duke) "Root image analysis"
2:30-3:00 Weitz Group (Georgia Tech) "Automated pipeline for root phenotyping and classification"
Break 3:00-3:30
Databases for imaging experiments
3:30-4:00 Sorger group (Harvard) "OME"
4:00-4:30 Mikhail Kovtun (Duke) "BISQUE"
4:30 Demonstrations of root imaging platforms
Previous Seminars
Tuesday, March 17, 2009
Dr. Eric H. Davidson
California Institute of Technology
147 Nanaline Duke
12:30pm
Reception to follow
Title: Towards A Global Gene Regulatory Network For Sea Urchin Development
Abstract: The endomesoderm gene regulatory network for sea urchin development is an experimentally obtained model of the genomic regulatory code directing embryonic specification of the skeletogenic mesoderm (SM), non-skeletogenic mesoderm and endoderm. The model is emplaced in the BioTapestry computational platform. Large parts of this model are now authenticated at the cis-regulatory level, and all known specifically expressed regulatory genes are incorporated in some regions as well. Novel very high throughput methods of cis-regulatory analysis greatly accelerate network authentication and improvement. As might be hoped according to the basic tenents of system biology, the most complete parts of the model, e.g. that relevant to SM specification, now provide causal explanation for virtually all biologically observed aspects of the developmental process. Network architecture also explains a dynamically changing spatial regulatory landscape. Network analysis is now extending to the oral and aboral ectoderm, and thus much of the embryo up to gastrulation is encompassed. Our goal is a global network in which all inputs derive from nodes within the network. It is clear that the network is modular in structure such that given subcircuits do given biological jobs, and different types of subcircuit evolve at different rates. Principles of developmental programming are emerging. These can be stated in terms of a set repertoire of subcircuit architectures which recur in different develop mental contexts and utilize the same structures, often built with different regulatory genes, to accomplish the same biological objectives.
Wednesday, April 1, 2009
Nick Buchler
Rockefeller University
2231 French Family Science Center
4:15pm
Refreshments at 4:00pm
Title: Bait and switch: How protein sequestration generates a flexible ultrasensitive response
Abstract: Regulatory networks in cells exhibit important dynamical behaviors, such as bistability (e.g. epigenetic switch) and oscillation (e.g. clocks, cell cycle). Ultrasensitive or `all-or-none’ gene expression is a necessary feature for the emergence of such dynamics in gene networks. In biology, many regulatory molecules are sequestered by an inhibitor into an inactive complex. Using an experimental approach in budding yeast, I will demonstrate how protein sequestration generates tunable, all-or-none thresholds in gene expression. A simple quantitative model for this genetic network shows that both the threshold and the degree of ultrasensitivity depend upon the abundance of the inhibitor, exactly as observed experimentally. The abundance of the inhibitor can be altered by simple mutation; thus ultrasensitive responses mediated by protein sequestration are easily tunable. Gene duplication of regulatory homodimers and loss-of-function mutations can create dominant-negatives that sequester the original duplicate into an inactive complex. These results suggest a mechanism for the rapid evolution of bistable switches and oscillators in regulatory networks.
Monday, March 2, 2009
Luis Carvalho
Brown University, Department of Applied Mathematics
116 Old Chemistry
4:25pm
Reception to follow
Title: Bayesian Centroid Estimation
Abstract: Maximum likelihood estimators have traditionally dominated discrete inference for a long time. In this work we apply statistical decision theory to derive a new contender that minimizes a posterior generalized Hamming loss: the centroid estimator. The centroid estimator is formally characterized as a solution to a discrete optimization problem having posterior marginal distributions as inputs. We discuss both specific constraints of interest and broad conditions under which this optimization problem becomes tractable and provide further generalizations to centroid estimation. We illustrate centroid estimation with simple applications to stochastic grammar parsing, reconstruction of ancestral states given a phylogeny, and RNA secondary structure prediction. Finally, we offer a few concluding remarks and directions for future work.
January 12th, 2009
Duke IGSP Center for Systems Biology presents:
Terry Hwa, UCSD 2231
January 12, 4:15pm
French Family Science Center
Title: On growth, antibiotics, and evolution
Abstract: It is a grand goal of systems biology to make predictive connection between molecular level details and the physiology of an organism. In this talk, I will describe an attempt by my laboratory to do this for the growth physiology of E. coli. Surveying over 50 years of literature complemented by our own experiments, we developed a simple yet comprehensive theory for bacterial growth control. In three simple equations, the theory incorporates the elements of ribosome elongation, amino acid starvation, and metabolism, all essential for bacterial growth control. The theory makes quantitative predictions on a range of physiologically-important questions, e.g., the effect of cell growth on gene expression and the effect of gene expression on cell growth, and have been validated in most cases. Applied to antibiotics and the expression of antibiotic resistance, the theory predicts a novel feedback effect which is expected to lead to rapid evolution of antibiotic resistance. In the last part of the talk, I will describe experiments which take advantage of the rapid evolvability of the system to breed bacterial promoters de novo.
February 20th, 2008
Ilya Nemenman,
Los Alamos National Laboratory (CV)
3:30 PM, February 20, 2008
Rm 128 PHYSICS
Title: Exploring dynamics and function of small biochemical networks.
Abstract: In a recent article in APS News, John Hopfield, one of the founders of what has now become quantitative and systems biology, has defined physics as "The idea ... that the world is understandable." As a physicist working on biological problems, I pursue this understanding as the ultimate goal. Unfortunately, even for the simplest cellular networks, understanding their function is often obscured behind long part lists of interaction partners, wiring diagrams, and differential equations. In this talk, I will describe how ideas of statistical physics and information theory allow us to make small steps towards formulation of and answers to questions like: What are the signal processing capabilities of stochastic biochemical networks? Which functions can they perform? How important is stochasticity? How can we understand network dynamics without microscopic simulations? While addressing these questions, I will also show examples of cross-fertilization between physics and systems biology: on the one hand, physics will suggest tools for faster simulation and deeper understanding of the networks dynamics, and, on the other, study of a biological problem will show an unexpected and illuminating connection between seemingly unrelated areas of theoretical physics.
Coffee and cookies before the presentation at 3:15 pm, and refreshments after the presentation will both be served in Room 128.
February 18th 2008
Amy Schmid, Institute for Systems Biology (CV)
4:15pm, Monday, February 18, 2008.
French Family Science Center Room 2231
Title: Systems biology in archaea: anatomy of cell state transitions in response to oxygen.
Abstract: Adjustment of physiology in response to changes in oxygen availability is critical for the survival of all organisms. However, the chronology of events and the regulatory processes that determine how and when changes in environmental oxygen tension result in an appropriate cellular response is not well understood at a systems level. Therefore, transcriptome, proteome, ATP, and growth changes were analyzed in a halophilic archaeon to generate a temporal model that describes the cellular events that drive the transition between the organism’s two opposing cell states of anoxic quiescence and aerobic growth. According to this model, upon oxygen influx, an initial burst of protein synthesis precedes ATP and transcription induction, rapidly driving the cell out of anoxic quiescence, culminating in the resumption of growth. This model also suggests that quiescent cells appear to remain actively poised for energy production from a variety of different sources. Dynamic temporal analysis of relationships between transcription and translation of key genes suggests several important mechanisms for cellular sustenance under anoxia as well as specific instances of posttranscriptional regulation. In the future, research in my laboratory will be directed toward understanding the mechanisms behind these posttranscriptional regulatory processes in response to oxygen in an archaeal model organism.
February 11th, 2008
Suzanne Gaudet, Harvard Medical School Monday
4:15pm February 11, 2008
French
Family Science Center Auditorium Room 2231
Title: Regulation of apoptosis by death-receptor ligands: a systems perspective
Abstract: The appropriate control of cell death in multicellular organisms is critical to homeostasis and health. While death receptor ligands promote cell death by activating caspases, these pro-death signals can be opposed by pro-survival signals in vivo. How do cells weigh these opposing signals to make a decision to die or to live? To tackle this question, two types of computational modeling approaches are combined with quantitative measurements from single cells and populations of cells. First, detailed mechanistic models of relevant signaling networks are used to investigate which factors control caspase activation dynamics. Second, descriptive, data-driven models have led to the exciting discovery of a TNF-induced autocrine cascade, providing evidence for the involvement of a network of extracellular signals in the cell death decision. These examples show how two different systems-level approaches have led to distinct types of insights in the cell death decision process.