My current PhD project involves dissecting out minor variants that contribute to, and modify, antimalarial drug resistance in Plasmodium falciparum. I've only just got started - watch this space!
During my time as an Advanced Research Assistant, I worked with colleagues in 8 different Universities and Institutions as part of the Malaria Drug Accelerator (MalDA) Consortium, consisting of the University of California San Diego, Columbia University, The Pennsylvania State University, Washington University in St. Louis, Harvard School of Public Health, Wellcome Sanger Institute, GlaxoSmithKline, The Medicines for Malaria Venture, and the Bill & Melinda Gates Foundation, which funded our project.
Our aim is to streamline the process of:
- identifying anti-malarial compounds
- determining their mode of action
- developing promising compounds into new antimalarial drugs
Ongoing work has identified mutations in Plasmodium falciparum, the malaria parasite, that are associated with resistance to a panel of chemical compounds. I recapitulate single alleles into a reference P. falciparum strain to determine the precise contribution of candidate mutations to the resistance phenotype:
I participate in the entire validation workflow; design and generation of CRISPR-Cas9/knock-in integration plasmids, transfection into parasites, genotyping of the resulting lines, and phenotyping by dose-response assays.
In a year and a half, I generated 67 plasmids, transfected 92 times, and performed over 100 drug assays.