Dr. Paul Bowyer, London School of Hygiene and Tropical Medicine, London
Monday 3rd March 2014, 4.00 p.m., Marlowe Lecture Theatre 1
The asexual bloodstages of the malaria parasite, Plasmodium falciparum, are responsible for the majority of the clinical symptoms of disease and are therefore attractive targets for chemical and vaccine based therapies. This talk will focus on just a few minutes of the 48-hour asexual cycle as the parasite first exits the red blood cell and, after a brief extracellular phase, then enters a new one.
The first portion of the talk will focus on the c-GMP dependent protein kinase (PKG) as a target for small molecule inhibitors. This protein is known to be essential for escape of the parasite from the host cell and I will describe the chemical genetic screens used to develop improved, selective inhibitors of PKG.
The second part of the talk will describe on-going work investigating the diversity of routes by which the extracellular merozoite (parasite) gains access to a new red blood cell. Many proteins exposed on the surface of the merozoite have been the subject of vaccine discovery programmes but the extent of allelic variation within the exposed proteins and the ability of the parasite to tolerate different ligand : receptor combinations during invasion complicates the process of antigen selection. Work investigating the diversity of ligand-receptor interactions involved in invasion pathways of fresh P. falciparum isolates, across a gradient of transmission intensity in West Africa, will be described.