James McCarthy-Projects

James McCarthy-Projects


Development of transmission blocking drugs

The gametocyte stages of development represent a bottleneck 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 affects transmission by mosquitos. The development and study of transmission-blocking drugs and vaccines will be essential in the fight to eliminate malaria.

Team member: Matthew Dixon


Microscope view
Giemsa stained thin blood film of gametocyte infected RBCs. Image credit: Matthew Dixon


Going bananas for sex

Gametocyte maturation and development is critical for survival within the host and disease transmission. Inhibition of this development would ablate disease transmission. This transformation sees an amoeboid-shaped asexual stage parasite morph into a banana-shaped sexual stage parasite, which is essential to disease transmission.

Despite the importance of this stage of the parasite we understand very little about its unique biology. This unique shape is driven by the assembly of a membrane complex termed the inner membrane complex and the elaboration of a dense microtubule cytoskeleton that drives the unique gametocyte shape. In this project we are interested in determining the cellular and molecular players driving this shape change and how this influences survival within the host and mosquito transmission.

Team members: Matthew Dixon


Microscope view
Super resolution microscopy image of a stage III Plasmodium falciparum gametocyte, highlighting the microtubules (green) and the inner membrane complex (red).
Parkyn Schneider et al, PLoS pathogens 2017, DOI: 10.1371/journal.ppat.1006659


The Renovators Dream: Malaria host cell remodelling

The ability of the malaria parasite to survive within the host relies on its ability to renovate its RBC home.

This renovation is facilitated by the export of proteins into the host cell, where they modify the RBC's properties making them rigid and prone to clearance by the spleen. To avoid clearance the parasite builds a multi-protein complex at the RBC surface called the virulence complex consisting of the knob protein KAHRP and the adhesin (PfEMP1).

We are interested in understanding how this complex is assembled and defining its molecular structure.

Team members: Matthew Dixon, Mohini Shibu


Microscopy view of plasmodium parasite protein
dSTORM super resolution microscopy image of the Plasmodium falciparum knob protein KAHRP.
Looker et al, PLoS pathogens 2019, DOI: 10.1371/journal.ppat.1007761