Lewis Strachan

PhD thesis: Conditional genetic screening of Plasmodium falciparum essential genes

My PhD focuses on identifying and studying genes of unknown function in Plasmodium falciparum, the parasite that causes almost all malaria mortality. About 35% of P. falciparum genes have unknown functions due to a lack of sequence homology with genes from more studied model organisms. Of the genes which have annotated functions, the majority are putative without any form of functional validation. This means that for most proteins in the malaria parasite, we do not know with any reasonable certainty what they do.

Previous large-scale transposon mutagenesis approaches have broadly identified genes that appear to be essential for growth during the blood stage of infection, but this technology does not provide any functional information about whether specific genes are required for specific biological processes. I will explore using CRISPR/Cas9 and conditional knockout approaches to scale up study of these ‘essential’ genes. I will initially target a family of genes likely involved in the invasion of human red blood cells by parasites and then explore whether this approach can be scaled at a higher throughput, using automated culture technologies. It is hoped that this work might identify essential genes whose products could be targeted by drugs or vaccines.

Who or what inspired you to pursue your research interests?:

My interest in parasites unexpectedly started with a course essay I wrote in my undergrad on honey bee parasitic mites. This led me to work on a research project understanding how parasitic worms manipulate the immune system of their mammalian hosts. My current work on the malaria parasite is driven by its enormous impact on human health and its unique cell biology.