Functional characterization of unique parasite-specific mitochondrial carrier proteins
Malaria parasites belong to an ancient clade of single-cell eukaryotes. They harbour a single mitochondrion that is a suitable target for anti-malarial drug development (e.g. atovaquone). While the mitochondrion is essential for all malaria parasite stages alike, there are major changes in morphology as well as function. Transport processes of metabolites involved in the many (changing) metabolic processes happening in the mitochondrial matrix are likely to contribute. Here, we propose the comprehensive functional profiling of three apicomplexan-specific mitochondrial carriers (AMC) that are expressed in asexual and sexual blood-stages, using complementary approaches in in vitro cultured human malaria parasites and an in vivo mouse model. These studies will further our understanding of parasite mitochondrial functioning as well as highlighting novel targets for antimalarial drug development. Transport proteins are generally considered excellent drug targets and the absence of human orthologues should minimize unwanted off-target effects. This project is done in collaboration with Manuel Llinás (Penn State Univ, USA) and Edmund Kunji (MBU-MRC/Univ Cambridge, UK).
Cas is fascinated by the molecular interaction that are behind cellular processes, ideally in non-model organisms. It is the molecular biology and not so much the pathology that drive his passion for science. Besides research, Cas highly values the transfer of knowledge through science communication and education. You can find some of his communication efforts under the “Visuals” tab, where he interviews a Vici grant winner, discusses the secrets of Cum Laude PhD graduates and highlights the efforts towards a greener Radboudumc. If you ever bump into Cas at a conference, but don’t know what to talk about, you can always start talking about specialty coffee or cycling. Two totally unrelated passions that can keep him occupied for hours.
(The picture shows live co-localization of P. berghei prohibitin 2 tagged with mCherry with our mitochondrial marker protein. Image taken from Matz et al. Cell Rep 2018.)