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Research Fellows Directory

Matthew Higgins

Dr Matthew Higgins

Research Fellow

Organisation

University of Cambridge

Research summary

Malaria is the most deadly parasitic disease to affect humanity, causing 500 million serious cases and 2 million deaths each year. Most of the deadly symptoms occur while the parasite lives and divides within human red blood cells. These infected red cells undergo many changes, making them ideally suited as a home for the parasite. One of these changes is the formation of tiny lumps, called knobs, on the red cell surface. Adhesive proteins, known as PfEMP1 proteins, are clustered at these knobs, causing infected red cells to become sticky. This results in many of the symptoms of the disease. Sticky red cells form clumps, called rosettes, which block tiny blood vessels in the brain, leading to coma and death during cerebral malaria. Sticky cells also cluster on the surface of the placenta of pregnant women, leading to disruption of blood flow to the developing foetus and often to loss of the child.

We study many aspects of the adhesion of infected red cells to human tissue, trying to understand precisely how PfEMP1 proteins bind to their receptors. This year we have progressed with our studies of the PfEMP1 proteins that bind to the surface of the placenta and to receptors within the brain. We have also shown that antibodies that bind to these domains are able to prevent interactions that lead to pathology. This means that the PfEMP1 proteins are valuable vaccine components that could be used to prevent the most dangerous symptoms of malaria. We are continue to study the molecular components involved in knob formation and PfEMP1 protein clustering. In all of this we aim to better understand the way that the malaria parasite causes disease, and to attempt to target these interactions with drugs and vaccines to prevent the severe symptoms of malaria.

Grants awarded

Structural studies of the binding of malaria surface proteins to human tissue.

Scheme: University Research Fellowship

Dates: Sep 2005 - Sep 2010

Value: £310,522.48