SURF 2012: Understanding feedback in bacterial toxin–antitoxin systems
2012 SURF project description
- Mentor: Richard Murray
- Co-mentor: Dan Siegal-Gaskins
Despite being found throughout the prokaryotic kingdom, toxin–antitoxin (TA) systems remain mysterious with regard to their precise role in biology. Generally, TA systems are composed of two genes, one of which has a toxic effect on the cell and the other which prevents the toxin from reaching its target. In addition to the effect that interaction with antitoxin has on the amount of free toxin in the cell, the concentration of toxin is also controlled with negative regulation at the transcriptional level.
Understanding the interplay between the steric interaction with antitoxin and the negative transcriptional feedback is the goal of this project. Students will develop detailed mathematical models of TA systems and explore in silico toxin dynamics as well as the effect of redundancy in feedback. In parallel with these theoretical efforts, a well- characterized TA system will be used to validate theoretical predictions. An important component of this work will be to develop the experimental tools necessary to monitor toxin–target binding and transcriptional regulation in real–time.
References
- Fiebig, A., Castro Rojas, C. M., Siegal-Gaskins, D., & Crosson, S. (2010). Interaction specificity, toxicity and regulation of a paralogous set of ParE/RelE-family toxin-antitoxin systems. Molecular Microbiology, 77(1), 236–251.
- Gerdes, K., Christensen, S. K., & Løbner-Olesen, A. (2005). Prokaryotic toxin-antitoxin stress response loci. Nature Reviews Microbiology, 3(5), 371–382.
- Mochizuki, A., Yahara, K., Kobayashi, I., & Iwasa, Y. (2006). Genetic addiction: selfish gene's strategy for symbiosis in the genome. Genetics, 172(2), 1309–1323.
- Van Melderen, L., & Saavedra De Bast, M. (2009). Bacterial toxin-antitoxin systems: more than selfish entities. PLoS Genetics, 5(3), e1000437.
- Yamaguchi, Y., & Inouye, M. (2011). Regulation of growth and death in Escherichia coli by toxin-antitoxin systems. Nature Reviews Microbiology, 9(11), 779–790.
