Throughout its complex lifecycle the malaria parasites, from the genus Plasmodium, must traverse tissues and invade a diversity of host cells to ensure successful propagation of their lifecycle. Each lifecycle stage is exquisitely designed for cell movement, tissue targeting, host cell invasion and replication, yet we still do not understand the basic mechanics of many of these key processes. Driven by this interest in the parasite journey, our work covers the entirety of the parasite's lifecycle adventure from human blood to mosquito and back again. Whilst our new interests are diverse they are unified under a common theme of dissecting fundamental processes in parasite biology and taking these insights to find and test new drugs that might block the journey and as such stop malaria disease.
Below you will find links to some of our key areas of research, with an example paper...
Vaccines | the global control of malaria needs surveillance and a vaccine. If we don't embrace the entire picture of malaria we will always be playing catch up with one of our oldest foes. We've been working hard on developing new technologies for subunit and whole vaccine technologies which we are pursuing with support from the Gates Foundation and Wellcome to walk the walk of developing a malaria vaccine. Watch this space!
Diagnostics | To transform surveillance and guide stratified measures to control malaria, we've been working closely with colleagues at Imperial, specifically Pantelis Georgiou and Aubrey Cunnington, and beyond to develop digital point of care diagnostics to identify malaria on site and immediately epidemiologically map it. Our first papers together on this are here. Watch this space as Lacewing technology takes flight.
Malaria parasite invasion of the human red blood cell | this is one of our longest running interests in the lab, focussed on dissecting the molecular and cellular events of invasion, but also the mechanics involved. Our most recent paper is available now as a preprint on BioRxiv. In recent years we've started to extend this interest in invasion to parts of the lifecycle beyond the blood stages - most importantly the liver stages. If you are interested in sporozoites, watch this space for updates!
Targeting the process of malaria parasite transmission, focussed on gametogenesis | we have ongoing programmes with the Medicine for Malaria Venture, screening for new drugs that target parasite biology - in particular the process of transmission to the mosquito. Among the many screens we've undertaken, check out our recent paper published together with colleagues at GSK - a massive first in kind screen of 70,000 compounds looking for new transmission blockers (Delves et al 2018). Our favourite from the screen... 007. Watch this space as we try and develop it into a real drug.
Protein translation in the malaria parasite | In 2014 we published the first ever structure of the malaria parasite ribosome. We've since followed this up with the structure of the ribosome in complex with the antimalarial mefloquine (see Wong et al, Nature Microbiology 2017) and continue to work actively in the area of drug discovery targeting protein translation. Our in vitro translation platform is currently live pre-publication at BioRXiv and we're working on IVT platforms and their application from drug discovery, protein expression to vaccinology.
The malaria parasite actomyosin motor | with continued funding from the Human Frontier Science Programme we have maintained our ongoing interests into how the actin-myosin motor systems of the malaria parasite work, from structure to function. From the essential light chain we co-discovered a few years back to the publication in 2020 of the full length crystal structure of the malaria parasite gliding motor. We've waited years for this! We continue to explore both actin and the other myosin motors in depth.