Our model systems are the trypanosomes, parasitic protozoa that are the causative agent of devastating parasitic diseases such as sleeping sickness, leishmaniasis and Chagas’ disease, which affect millions of people worldwide.
In my laboratory, we are investigating processes which are unique to the parasite and not found in the mammalian host; our hope is to find unique targets for therapy.
We focus on the structure and function of RNA molecules that participate in RNA processing trans-splicing that is unique to these parasites. We are interested in the structure and function of novel anti-sense non-coding RNAs and the mechanism of a novel RNAi silencing event discovered in our laboratory, snoRNAi, which silences nucleolar RNAs. Recently, we discovered a novel stress-induced mechanism that silences the production of mRNA by abolishing trans-splicing that leads to apoptosis. We term this process SLS, and plan to identify chemical compounds that elicit this death pathway as potential chemotherapy.
We study the mechanism of protein sorting across the ER, especially the role of the signal recognition particles (SR), since we found that the trypanosome particle carries two RNA molecules unlike all its homologues in other eukaryotes. In addition, we study unique RNA quality control mechanisms that regulate the level of non-coding RNAs.
My laboratory is also investigating nuclear RNA silencing in human cells and exploring the use of nanotechnology for gene silencing.
We were heavily involved in generating transgenic plants resistant to nematodes by expressing siRNAs to silence pathogenic plant nematodes.
We use a variety of methodologies from generating of transgenic parasites, knock-out, RNAi silencing, biochemical fractionation of RNA-protein complexes, microarray analysis of the transcriptome, and live cell imaging of RNA, proteins and more.