Last Updated: 04/12/2025
Overcoming antigenic variation by genome editing technology
Objectives
This project aims to overcome antigenic variation in the parasite Plasmodium falciparum, which evades immune recognition through a system of surface proteins called PfEMP1.
Parasitic protozoa cause a plethora of human and veterinary diseases that have devastating impacts on human health and the economy. Effective vaccine against these protozoa is not available even for the most well-studied malaria parasite Plasmodium falciparum. These protozoa are equipped with a decoy system to overcome human immunity. In P. falciparum, a series of surface proteins called PfEMP1 are expressed on the red blood cell surface for adhesive binding to blood vessel lining in order to avoid being filtered out by spleen. Each P. falciparum keeps shuffling between approximately sixty PfEMP1 proteins to evade immune recognition. This phenomenon is called ‘antigenic variation’. The mechanism underlying antigenic variation is not known, but several epigenetic factors including histone modification and non-coding RNA are responsible for gene silencing. To have a successful malaria vaccine, it is imperative that an approach must be developed to overcome antigenic variation. Here a team of scientists from the Wellcome Trust Sanger Institute and Mahidol University will work together to apply advanced genome editing techniques to target antigenic variation. A modified parasite can be a novel candidate for vaccine development. The research is conducted in collaboration with the laboratories of Drs. Oliver Billker, Julian Rayner and Marcus Lee at the Wellcome Trust Sanger Institute.
Mar 2016 — Mar 2018
$94,863
