As manager of the Imperial-Medicines for Malaria Venture Centre of Excellence, my main research interest is to understand the complex cell biology of Plasmodium transmission stage development and use this knowledge to help discover new drugs to eradicate malaria.
Plasmodium transmission to the mosquito is mediated by the sexually dimorphic male and female gametocytes. In P. falciparum, gametocyte development takes ~10 days, and maturation is linked to loss of sensitivity to most antimalarials. This can cause the unfortunate situation in which a malarial patient can be cured of disease symptoms triggered by the asexual parasites, but are left with gametocytes that are still infectious to mosquitoes thus perpetuating the disease cycle. Eradication of malaria will require new therapies to prevent parasite transmission to the mosquito.
I have recently shown that male gametocytes are more drug-sensitive than female gametocytes and so optimum drug discovery should take advantage of this weakness. To this end I have developed high throughput assays to screen small molecule libraries against both male and female gametocytes simultaneously to identify new lead transmission-blocking molecules. Additionally, little is known about how the gametocyte prepares for onward transmission. My work also aims to better understand the fine balance between quiescence and explosive development in mature gametocytes.
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
et al., 2017, Hundreds of dual-stage antimalarial molecules discovered by a functional gametocyte screen., Nat Commun, Vol:8
et al., 2017, Antimalarial efficacy of MMV390048, an inhibitor of Plasmodium phosphatidylinositol 4-kinase, Science Translational Medicine, Vol:9, ISSN:1946-6234
et al., 2016, Discovery of a Quinoline-4-carboxamide Derivative with a Novel Mechanism of Action, Multistage Antimalarial Activity, and Potent in Vivo Efficacy, Journal of Medicinal Chemistry, Vol:59, ISSN:0022-2623, Pages:9672-9685
et al., 2016, Corrigendum: A novel multiple-stage antimalarial agent that inhibits protein synthesis., Nature, Vol:537