BME PhD Dissertation Defense - Christopher Garay

Starts:
10:00 am on Wednesday, December 11, 2013
Location:
44 Cummington Mall, Room 203
TITLE:
Metabolic Model of Mycobacterium tuberculosis through the Integration of Large-Scale Genomics Datasets

COMMITTEE:
Dr. James Galagan, Department of Biomedical Engineering (Advisor)
Dr. James Collins, Department of Biomedical Engineering (Chair)
Dr. Daniel Segre, Bioinformatics Program
Dr. Martin Steffen, Boston University School of Medicine

ABSTRACT:
Mycobacterium tuberculosis (MTB) is the bacterium that is the causal agent of tuberculosis. MTB is estimated to infect one-third of the world's population. The emergence of multi drug-resistant and extensively drug-resistant strains of the bacterium are becoming a larger threat to global health as they decrease the efficacy of current treatments and make the disease more fatal. These factors combine to make MTB an interesting target for study with novel systems biology approaches. Genome-scale metabolic models have emerged as important platforms for the analysis of datasets that describe highly-interconnected biological processes. We have the first comprehensive profiling of mRNA, proteins, metabolites, and lipids in MTB during an in vitro model of infection that includes a time course of induced hypoxia and re-aeration. Hypoxia and re-aeration are important cues during infection of the human host and act to model the environment seen in the host. We utilize genome-scale metabolic modeling methods to integrate these data with our metabolic model will allow us to generate experimentally-testable predictions about metabolic adaptations that occur in response to experimental perturbations that represent an in vitro model of important environmental cues present during infection, dormancy, and re-activation in the human host.