Malaria is still a disease with devastating impact in the poorest regions of the world, with drug resistance an ever-present problem. Plasmodium, the parasite responsible for malaria has a complex life cycle requiring both human and mosquito hosts. The onward spread of the disease and drug resistant genes can only happen through transmission to mosquitoes. Male and female gametocytes are the "gatekeepers" of parasite transmission; residing quietly in the blood before explosively transforming in the mosquito midgut to ensure onward infection.
My research aims to understand these gametocyte stages with a view to identifying new drugs to prevent malaria transmission. Using high throughput/high content screening techniques I have developed an assay that simultaneously reports on the viability of male and female gametocytes - the P. falciparum Dual Gamete Formation Assay (Pf DGFA). This assay is now the standard go/no-go decider for early stage antimalarial drug development at the Medicines for Malaria Venture (MMV). Through our position as a MMV Centre of Excellence that I helped establish with Prof Robert Sinden in 2009 and continuing with Prof Jake Baum, I collaborate with numerous academic and Big Pharma antimalarial research programmes.
Pf gametocytes are notoriously difficult to culture to maturity. Through numerous failures I have developed and published standard protocols to streamline and simplify the process. We regularly train external labs in our techniques and welcome collaborations. Using this flexible culturing system I seek to understand more about the fascinating cell biology of gametocytes, in particular the amazing process of male gamete formation (exflagellation) that causes one quiescent cell to transform into eight motile cells in less than 20min. Additionally, I study how drug resistance affects gametocytes and its implications for transmission.
et al., 2017, 3-Hydroxy-N '-arylidenepropanehydrazonamides with Halo-Substituted Phenanthrene Scaffolds Cure P. berghei Infected Mice When Administered Perorally, Journal of Medicinal Chemistry, Vol:60, ISSN:0022-2623, Pages:6036-6044
et al., 2017, A tetraoxane-based antimalarial drug candidate that overcomes PfK13-C580Y dependent artemisinin resistance, Nature Communications, Vol:8, ISSN:2041-1723
et al., 2017, Hundreds of dual-stage antimalarial molecules discovered by a functional gametocyte screen, Nature Communications, Vol:8, ISSN:2041-1723
et al., 2017, Antimalarial efficacy of MMV390048, an inhibitor of Plasmodium phosphatidylinositol 4-kinase, Science Translational Medicine, Vol:9, ISSN:1946-6234
et al., 2017, Adaptation of targeted nanocarriers to changing requirements in antimalarial drug delivery, Nanomedicine-nanotechnology Biology and Medicine, Vol:13, ISSN:1549-9634, Pages:515-525