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[Colloquium] Quantitative Analysis and Simulation of Latency-Related Pathways in a Murine Model of Mycobacterium tuberculosis Infection
October 2, 2009
- Date: Friday, October 2nd, 2009
- Time: 12 pm — 12:50 pm
- Place: Centennial Engineering Center, Room 1041
Elebeoba E. May
Sandia National Lab
Abstract: Tuberculosis (TB), caused by the bacterium Mycobacterium tuberculosis (Mtb), is a growing international health crisis. Mtb is able to persist in host tissues in a nonreplicating persistence (NRP) In vitro models have identified enzymes and associated pathways up regulated during NRP, which are thought to supply energy through alternative pathways to the biosynthetically restricted pathogen (Wayne and Sohaskey, 2001). In the hypoxic model of NRP, the tubercle bacilli can circumvent the shortage of oxygen by developing alternative energy generation mechanisms using pathways such as those involved in the glyoxylate-to-glycine shunt (GtG) that may serve to replenish NAD (Wayne and Sohaskey, 2001; Wayne and Lin, 1982). Using Michaelis-Menten and mass action kinetics, data from MetaCyc, and initial rates from BRENDA, we are constructing a BioXyce model of M.tuberculosis that includes pathways identified through in vitro and in vivo studies. Simulation and analysis of NRP-relevant pathways will enable quantitative assessment of the molecular basis of latency and reactivation in murine models of infection.
This work is supported by an NIH/NHLBI grant 5K25HL75105-3. Sandia is a multiprogram laboratory operated by Sandia Corporation, a Lockheed Martin Company for the United States Department of Energy’s National Nuclear Security Administration under contract DE-AC04-94AL85000.
Bio: Dr. Elebeoba E. May received her Ph.D. in computer engineering from North Carolina State University and is a Principle Member Technical Staff in Sandia National Laboratories Discrete Mathematics and Complex Systems Department. She is an Adjunct Research Assistant Professor in UNM-HSC’,s Internal Medicine Department with a joint appointment as an Adjunct Research Assistant Professor in UNM’s Electrical and Computer Engineering Department. Her research interests include the use and application of information theory, coding theory, and signal processing to the analysis of genetic regulatory mechanisms, the design and development of intelligent biosensors, and large-scale simulation and analysis of biological pathways and systems. Since joining SNL, Dr. May has provided computational biology leadership in the development of BioXyce, a large-scale systems biology simulation tool and continues leading development efforts in the application of BioXyce to simulation-based studies of host/pathogen interactions.
Dr. May is a recipient of the 2003 and 2008 Women of Color Research Sciences and Technology Award for Outstanding Young Scientist or Engineer and an NIH/NHLBI K25 Quantitative Research Career Development Grant to quantitatively decipher the genetic basis of latency in M. tuberculosis infection.
