Project Summary
In 2003, I began collaborating with Dan Zilberstein at the Technion – Israel Institute of Technology to utilize the rapidly emerging tools available for genome-wide elucidation of changes in gene expression occurring during Leishmania promastigote-to-amastigote differentiation, using an axenic system that his group had established. The collaboration has proven remarkably fruitful, as we used a USI-BSF grant to support microarray and LC-MS/MS analysis and show that there is a well-coordinated program involved changes in mRNA and protein abundance of several hundred genes during this differentiation process – challenging the dogma at the time, which held that trypanosomatid gene expression was generally constitutive. This work as continued with the introduction of new technologies, such as RNA-seq, ribosome profiling (in collaboration with Marilyn Parsons at CID Research) and phosphoproteomic analyses, to generate the extensive datasets needed for a true systems approach to understanding the molecular processes involved in Leishmania differentiation. I have also collaborated with other Leishmania researchers to extend these analyses to identify the regulatory networks underlying the response to other environmental stimuli, and we are now on the brink of being able to test some of these hypotheses experimentally.
- Saxena A, Lahav T, Holland N, Aggarwal G, Anupama A, Huang Y, Volpin H, Myler PJ, Zilberstein D. (2007) Analysis of the Leishmania donovani transcriptome reveals an ordered progression of transient and permanent changes in gene expression during differentiation. Mol Biochem Parasitol, 152:53-65. PubMed: 17204342; PubMed Central: PMC1904838.
- Lahav T, Sivam D, Volpin H, Ronen M, Tsigankov P, Green A, Holland N, Kuzyk M, Borchers C, Zilberstein D, Myler PJ. (2011) Multiple levels of gene regulation mediate differentiation of the intracellular pathogen Leishmania. FASEB J, 25:515-525. PubMed: 20952481
- Mittra B, Cortez M, Haydock A, Ramasamy G, Myler PJ, Andrews NW. (2013) Iron uptake controls the generation of Leishmania infective forms through regulation of ROS levels. J Exp Med. 210:401-16. PubMed PMID: 23382545; PubMed Central PMCID: PMC3570109.
- Martin JL, Yates PA, Soysa R, Alfaro JF, Yang F, Burnum-Johnson KE, Petyuk VA, Weitz KK, Camp DG 2nd, Smith RD, Wilmarth PA, David LL, Ramasamy G, Myler PJ, Carter NS. (2014) Metabolic reprogramming during purine stress in the protozoan pathogen Leishmania donovani. PLoS Pathog, 10:e1003938. PubMed PMID: 24586154; PubMed Central PMCID: PMC3937319.