Research highlights: Team Cytoskeleton
Plasmodium life cycle: The parasite needs to actively move at various stages in order to complete its life cycle (red arrows). Understanding this movement will provide more information for potential future interventions.
See more at: Douglas et al (2015) Trends in Parasitology 31(8):357-362
Mutations in Plasmodium actin result in aberrant motility. Wild-type parasites usually move smoothly, while certain actin mutant parasites stall.
See more at: Douglas et al. (2018) PLOS Biology 16(7):e2005345
Visualizing actin filaments in parasites. An actin chromobody reveals distinct locations of actin filaments in sporozoites. In the case of an actin mutant, the localization resembled that of stabilized filaments.
See more at: Yee et al. (2022) PLOS Pathogens 18(8):e1010779
Research focus
The malaria-causing parasite Plasmodium has to replicate and spread 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 body temperature. The parasite thus needs a genetic repertoire and, importantly, an adaptable cytoskeleton dynamic 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 the classical mammalian cytoskeleton. For example, Plasmodium actin 1 forms unstable filaments that tend to be only very short. These short filaments are crucial in allowing one particular stage of the parasite (the sporozoite) to move up to 10x faster than mammalian cells, essentially letting the parasite outrun our own immune cells! In addition, 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, how these regulate highly unstable actin filaments and the consequences of this for parasite transmission.
The primary interest of the research group is in understanding the contribution of divergent Plasmodium cytoskeleton dynamics towards parasite progression, particularly to and 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 stop the parasite at various stages of its life cycle.
We are always interested to receive applications from highly motivated individuals for Masters, Doctoral, and Postdoctoral positions. Interested persons can write to Ross Douglas directly, please include your CV and academic transcripts.