FORMIN · Structural and functional studies on Plasmodium formins

Funding is applied to carry out research on formin-mediated regulation and dynamics of actin-based motility of apicomplexan parasites, such as Plasmodium, the causative agent of malaria. Formins are large multi-domain proteins, which regulate microfilament formation by triggering actin monomer addition from actin-profilin complexes at the barbed end. Formins bear two formin homology (FH) domains. Plasmodium FH2 domains are conserved with higher eukaryotes and are responsible for actin binding, while Plasmodium formins contain only putative short FH1 domains with a small number of prolines that could be recognized by proline-rich motif binding proteins, such as profilin. The aim of this study is to find out if these short proline-rich regions in apicomplexan formins are enough for recruiting profilin–actin complexes and to perform structural and biochemical/biophysical characterization of the formins and their binding partners. In addition, crystal and solution structures of the ternary complex actin-profilin-formin will be pursued. These data are expected to provide us with a structural basis for understanding the mechanism of actin-based motility in apicomplexan parasites. The host laboratory has excellent facilities for molecular biology, protein production as well as X-ray crystallography. I myself as the applicant have spacious knowledge in these methods. The planned visit will be the first post-doctoral period for me and will serve as an important step to develop my scientific career.