Elucidating Plasmodium induced complexity in the host signalling network

Intracellular pathogens must successfully engage and/or navigate the complex interactions of the host network to survive. To adapt, many parasitic species are promiscuous in their host cell choice but the Plasmodium sporozoite is exquisitely selective to a subset of hepatocytes. Beyond the cellular events that precede the productive establishment of replication niche in hepatocytes, the specific molecular interactions that mediate progression from invasion to development, remain poorly elucidated. In the next five years, Kamalakannan Vijayan aims to uncover this by asking the following questions, 1) Does the host-pathogen interaction at the cell surface alter the receptor landscape which facilitates infection? 2) how does the pathogen sequester the host nutrients? 3) can the parasite-rewired cell signalling be specifically exploited for antimalarial intervention? The work proposed here is in part based on the premise, established by the preliminary data that Plasmodium, (1) induces, and then utilizes the process of host lysosome exocytosis during invasion. (2) Sequesters host lipids by altering the cytoskeleton organization thereby reorienting the intracellular traffic. Together, these three aims will build upon our recent work and elucidate key processes that establish a permissive environment under which the malaria parasite thrives within the host.

Project details

Basic Science

Mar 2024 — Feb 2029

$437,879

India