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...
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. Check out two of our most recent paper in this area, published in 2017 and 2018 <Koch et al> and <Lyth et al>. 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 and Bill and Melinda Gates Foundation, 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 most recent paper published together with colleagues at GSK in Nature Communications - 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.
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. Last year we worked together with the group of Kathy Trybus in Vermont to explore the role of a new light chain in regulating the main myosin of Plasmodium myosin A <Bookwalter et al>. We continue to explore both actin and the other myosin motors in depth and the structure of the motor is now on its way (coming soon!).
Artemisinin drug resistance, Diagnostics and Vaccinology | Never sitting still (!) 2019, like before, will see us consolidate the new directions for the lab in vaccinology, diagnostics and exploring artemisinin drug resistance. Watch this space as the works start to mature into publications...! One platform for digital diagnostics already out - working together with Pantelis Georgiou at Imperial college <Malpartida-Cardenas et al>.