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.
Project Keywords: Bioinformatics, Genomics, Parasite Molecular Biology