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 new therapeutic targets 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. 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. Our focus is squarely on the sporozoite - aiming to stop malaria infection before disease takes hold. Guided by our recent collaboration with Mara Lawniczak's lab at Sanger, we're using our sporozoite atlas (Real et al 2021) to define new candidates for vaccine targeting. And some of our new sporozoite targeted approaches approaches are working... Watch this space!
Diagnostics | To transform surveillance and guide stratified measures to control malaria, we've been working closely with colleagues at Imperial College London, Pantelis Georgiou, Aubrey Cunnington, and Molly Stevens to develop both digital point of care diagnostics and lateral flow based transmission diagnostics to identify malaria on site, immediately map it and also determine whether an infection is likely to transmit. Our first papers together on this are here. Watch this space as the other technologies 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 on this was Tom Blake (former PhD student's) tour de force of myosin invasion biology. 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 worked with the Medicine for Malaria Venture for more than 7 years, screening for new drugs that target parasite biology - in particular the process of transmission to the mosquito (always keen to apply imaging - as we did in our most recent paper on this subject: Yahiya et al 2022). Among the many screens we've undertaken, check out our 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, Sabrina (a recently completed PhD student) has shown targets the transmission protein Pfs16 - see our preprint here.
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. Paper jointly with Dundee University coming soon....
The malaria parasite actomyosin motor | with back-to-back program 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.