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Spring 2008 Special Seminar (back to list)

March 5, 2008, 2 p.m.

James Galagan, Broad Institute of MIT and Harvard

"Integrated Genomics and Computational Systems Biology for Tuberculosis "

Abstract:

The combination of computational biology and genomic technology is providing new approaches to the study of microbiology and infectious disease.  For the first time we are in a position construct a comprehensive view of the molecular networks underlying microbial physiology and pathogenesis.  This in turn promises to have a direct impact on public health and clinical care.  In this talk I will describe computational genomic approaches to studying the metabolic and genetic networks of Mycobacterium tuberculosis , the causative agent of TB. 

Metabolic changes are a critical component of TB pathogenesis and latency. And many first line TB drugs target metabolism.  To better study TB metabolism, we developed computational methods to model metabolic networks.  In particular we have developed a novel approach to coupling expression array data with computational flux balance analysis to predict metabolic state from gene expression state.  I will describe this method and our application of it to predict the metabolic impact of drugs and environmental conditions on mycolic acid biosynthesis.  I will also describe a related method we developed to predict nutrient and environmental conditions from metabolic state predictions – a potential tool for investigating the phagosomal environment within which the intracellular pathogen TB lives.

Metabolic changes are orchestrated by gene regulatory changes, and I seek to understand the regulatory programs at work during TB pathogenesis at the level of genes, operons, and the full regulatory network.  I will describe our work to computationally annotate genes and operons, and in particular the development of a method for sequence annotation using Conditional Random Fields.  I will also describe our strategy to combine comparative analysis, expression mining, and Chip-Seq to map TB regulatory networks.  Ultimately, my goal is to derive an integrated model of TB metabolism and gene regulation that can be used to address fundamental questions concerning TB pathogenesis, persistence, and drug resistance.

This special seminar will be held at 2:00 p.m. in Rm. 1103 Biosciences Research Building

Past seminars: Fall 2004 Spring 2005 Fall 2005 Spring 2006 Fall 2006 Spring 2007 Fall 2007