June 29, 2022 5:06 pm

About us

We study the basic cellular and molecular mechanisms used by parasites to develop in their host. Our models include single cell-eukaryotic parasites belonging to the group kinetoplastids, which contains several species that are pathogenic to humans and animals. All pathogenic kinetoplastids are transmitted by insect vectors, in which the parasites go through distinct developmental programs. Kinetoplastids are the causative agents of diseases such as African sleeping sickness, Chagas disease, and leishmaniasis which threaten millions worldwide. There are currently no vaccines for these parasites making it imperative that we understand how they function to develop new ways to combat these diseases. In addition, these early diverging eukaryotes are fantastic models for basic cell and molecular processes shared by diverse species. We use a combination of microscopy, molecular, and genome-wide approaches to identify and analyze proteins of interest. There are two main areas of research in the lab:

Mitochondrial dynamics

A rosette of adhered C. fasciculata parasites expressing mitochondrial GFP (mitoGFP).

Pathogenic parasites must adapt their metabolism to survive in their different hosts. In some cases, these changes are accompanied by striking changes in mitochondrial shape, the mechanisms of which are completely unknown. We are interested in exploring this process as model for the relationship between organelle structure and function. These studies utilize the distinct advantages of Trypanosoma brucei and Crithidia fasciculata to address how mitochondrial shape relates to metabolic adaptation in different host environments.

Adhesion

C. fasciculata parasites expressing a cytoplasmic GFP adhered to the hindgut of an Aedes aegypti mosquito

Pathogenic kinetoplastids adhere to tissues in their insect host and this adhesion is required for them to complete their life cycle in the vector. We have found that free swimming flagellated cells of Crithidia fasciculata, a kinetoplastid parasite of mosquitoes, can rapidly and dramatically alter their cellular and gene expression programs to resemble the adherent, stationary forms observed in mosquitoes. This remarkable transformation seems to be driven by adhesion of swimming cells to tissue culture plastic.

Funding

This work is supported by an NSF CAREER grant (MCB-1651517) to Megan Povelones and an NIH R21 (1R21AI154022-01) to Megan and Michael Povelones (University of Pennsylvania School of Veterinary Medicine).