Higgins group homepage

Dr Matthew Higgins has now moved to the University of Oxford. His new address is:

Department of Biochemistry
University of Oxford
South Parks Road
Oxford
OX1 3QU

matthew.higgins@bioch.ox.ac.uk
Group page at Oxford

Current Research

Malaria, caused by the parasite, Plasmodium falciparum, is one of the most deadly diseases affecting humanity, causing some million deaths and hundreds of millions of serious cases each year. We use structural and biophysical methods to study proteins central to the pathology of this disease. We have a particular interest in the cell surface proteins of the parasite, as these are essential to many phases of the parasite life cycle, and form potential vaccine targets.

In particular, we focus on the PfEMP1 proteins. These are expressed on the surfaces of malaria-infected erythrocytes and cause adhesive phenotypes. This leads to the sequestration of infected erythrocytes throughout the body, allowing the parasite within to avoid detection and destruction by the spleen. Infected erythrocytes also accumulate within specific tissues, such as the brain and the placenta, contributing to pathology during cerebral and placental malaria.

We use structural methods to understand how these proteins interact with specific ligands on human tissues and also attempt to develop agents that can block these interactions.

In addition, in collaboration with Mark Carrington in Cambridge, we are interested in the cell surface proteins of the trypanosomes. Parasites of this family cause African sleeping sickness in both humans and cattle. Unlike malaria-causing parasites, trypanosomes remain in the blood stream where they are covered in a layer of variant surface glycoprotein, VSG, to protect them from detection by the immune system. We use structural methods to study receptor proteins from the trypanosome cell surface, aiming to understand how they recognise their ligands within a VSG layer.

Lab members
Alan Brown (Cambridge), Stephanie Glaser (Cambridge), Livia Lia (Oxford), Kate Wright (Oxford)

Structures

DBL6 Epsilon from var2csa

DBL3X [Proteopedia] [Proteopedia]

DBL3X in complex with sulphate [Proteopedia]

DBL6 Epsilon [Proteopedia]

References

Ghumra A, Khunrae P, Ataide R, Raza A, Rogerson SJ, Higgins MK, Rowe JA. Immunisation with recombinant PfEMP1 domains elicits functional rosette-inhibiting and phagocytosis-inducing antibodies to Plasmodium falciparum. PLoS One. 2011 Jan 31;6(1):e16414 [PubMed]

Barfod, L., et al. Chondroitin Sulfate A-Adhering Plasmodium falciparum-Infected Erythrocytes Express Functionally Important Antibody Epitopes Shared by Multiple Variants. J Immunol. 2010 Nov 15;185(12):7553-61 [PubMed]

Khunrae P, Higgins MK. Structural insights into chondroitin sulfate binding in pregnancy-associated malaria. Biochem Soc Trans. 2010 Oct;38(5):1337-41 [PubMed]

Brown A, Higgins MK. Carbohydrate binding molecules in malaria pathology. Curr Opin Struct Biol. 2010 Oct;20(5):560-6 [PubMed]

Khunrae P., Dahlb├Ąck M., Nielsen M.A., Andersen G., Ditlev S.B., Resende M., Pinto V.V., Theander T.G., Higgins M.K., Salanti A. (2010) Full-Length Recombinant Plasmodium falciparum VAR2CSA Binds Specifically to CSPG and Induces Potent Parasite Adhesion-Blocking Antibodies. JMB 2;397(3):826-34 [PubMed]

Khunrae, P., Philip, J.M., Bull D.R., and Higgins, M.K. (2009) Structural comparison of two CSPG-binding DBL domains from the VAR2CSA protein important in malaria during pregnancy. JMB 393(1):202-13 [PubMed]

Higgins, M.K. (2008) The structure of a chondroitin sulfate-binding domain important in placental malaria. JBC 283(32):21842-6 [PubMed]