Project: Development of transmission blocking drugs
The gametocyte stages of development represent a bottle neck in the malaria lifecycle with only a proportion (~10%) of the parasite population committing to sexual development. This makes the gametocyte an attractive drug target, as disruption of gametocyte development by a drug or vaccine would stop transmission. Using a combination of in vitro and ex vivo experiments and examination of ex vivo samples from experimental malaria infection studies, we will investigate the effects these drugs and vaccines have on male and female gametocytes. In addition, we will directly test how drug treatment effects transmission by mosquitos. The development and study of transmission blocking drugs and vaccines will be essential in the fight to eliminate malaria.
Our laboratory investigates the cellular mechanisms underpinning malaria parasite transmission and disease. We investigate the novel banana shaped sexual stages of Plasmodium falciparum, focused on understanding their unique biology and how this contributes to transmission. We are interested in developing and testing drugs and vaccines that may block transmission of the parasite from infected humans to Anopheles mosquitos.
Our research is aimed at understanding the unique biology of the malaria parasite Plasmodium falciparum, with a particular focus on virulence and transmission.
We are investigating:
- How parasites renovate their RBC home to drive virulence and transmission.
- How the parasite makes the banana shaped sexual blood stage gametocyte.
- How this shape helps them survive in the host and be efficiently transmitted.
- How parasites behave inside the human host in vivo.
- How effective specific drugs and vaccines are at blocking transmission of gametocytes from infected humans to Anopheles mosquitos.
In these projects, we will use CRISPR gene editing to create transgenic malaria parasites, which we will study by combing proteomics, molecular and cellular biology techniques with super resolution microscopy to define the molecular players driving gametocyte development and transmission. This in vitro work will be complimented by ex vivo examination of samples from experimental human malaria infection studies, which are focused on identifying and confirming the activity of candidate transmission blocking drugs and vaccines.
A combined in vitro and in vivo approach to understanding how gametocytes mature will inform the development of effective means of combating this debilitating disease.