Research focus of Dr. Ross Douglas
Dr. Ross Douglas
The malaria-causing parasite Plasmodium has to spread and replicate in various tissues and cell types to complete its complex life cycle in two different hosts. It has to do this in host environments that have very different immune responses, metabolism, and temperatures. The parasite thus needs a genetic repertoire and, importantly, an adaptable cytoskeleton that can cope with drastic changes to its environment in order to be effectively transmitted to the next host.
The Plasmodium actin cytoskeleton behaves differently; it is highly sequence divergent and has altered biochemistry compared to classical mammalian actins. For example, Plasmodium actin 1 forms unstable filaments that tend to be only very short. These short filaments are crucial in allowing the parasite to move up to 10X faster than mammalian cells, essentially letting the parasite outrun our own immune cells! Moreover, the parasite expresses a small family of actin binding proteins that are very different in apicomplexans. Very little is known about the roles of these proteins in the parasite and how these regulate highly unstable actin filaments.
The primary interest of the research group is in understanding the contribution of divergent Plasmodium cytoskeleton dynamics towards parasite progression, particularly through the mosquito. Our team uses parasite reverse genetics, imaging, and molecular biology techniques to unravel the contributors towards the altered properties of the parasite cytoskeleton. By understanding these processes and what exactly makes the parasite cytoskeleton functionally different, we will use this information in the generation of small molecules that could block the parasite at various stages of its life cycle.