Selected publications

• Kriek Neline, Tilley Leann, Horrocks Paul, Pinches Robert, Elford Barry C, Ferguson David JP, Lingelbach Klaus, and Newbold Chris I (2003) Characterization of the pathway for transport of the cytoadherence-mediating protein, PfEMP1, to the host cell surface in malaria parasite-infected erythrocytes. Mol Microbiol, 50(4):1215-27.

• Williams T N and Newbold C I (2003) Reevaluation of flow cytometry for investigating antibody binding to the surface of Plasmodium falciparum trophozoite-infected red blood cells. Cytometry A, 56(2):96-103.

• Gupta S, Snow R W, Donnelly C A, Marsh K, and Newbold C (1999) Immunity to non-cerebral severe malaria is acquired after one or two infections. Nat Med, 5(3):340-3.

• Kyes S A, Rowe J A, Kriek N, and Newbold C I (1999) Rifins: a second family of clonally variant proteins expressed on the surface of red cells infected with Plasmodium falciparum. Proc Natl Acad Sci U S A, 96(16):9333-8.

• Bowman S, Lawson D, Basham D, Brown D, Chillingworth T, Churcher C M, Craig A, Davies R M, Devlin K, Feltwell T, Gentles S, Gwilliam R, Hamlin N, Harris D, Holroyd S, Hornsby T, Horrocks P, Jagels K, Jassal B, Kyes S, McLean J, Moule S, Mungall K, Murphy L, Oliver K, Quail M A, Rajandream M A, Rutter S, Skelton J, Squares R, Squares S, Sulston J E, Whitehead S, Woodward J R, Newbold C, and Barrell B G (1999) The complete nucleotide sequence of chromosome 3 of Plasmodium falciparum. Nature, 400(6744):532-8.

Prof Chris Newbold

About one third of the way through the 48 hour cycle of growth and division within red cells, parasite encoded proteins are exported to the red cell membrane. Some of these associate with the red cell cytoskeleton and others are inserted into the membrane and are accessible from the exterior. These latter proteins are encoded by large variant multigene families and mediate adhesion to a variety of host cell types. As a result parasitised red cells concentrate in various organs and cause damage by binding to endothelial cells, bind to uninfected red cells forming red cell rosettes which may further reduce blood flow to critical sites, or may bind to dendritic cells inhibiting their activation.Many different host receptors can be utilised depending on the particular parasite genes expressed and this is related to parasite tissue distribution and disease severity. In order to evade the protective host antibody response that is mounted against these parasite proteins, switching between different members of the multi-gene families leads to antigenic variation.

Our group seeks to study the molecular basis for adherence related pathogenesis, antigenic variation and immunity through:

• Identification of host receptors involved and the role of binding to individual receptors in severe disease.
• Understanding these interactions at the molecular level.
• Understanding the role of different parasite multi-gene families in adhesion and identifying binding sites.
• Determining how antigenic variation is controlled at the molecular level.
• Determining how the natural immune response evolves to these variant proteins and understanding the role of epitope specific antibody responses in protection
• Understanding how parasites proteins become exported through the cytoplasm of a cell that has no protein trafficking machinery.
  

To achieve these aims we have taken a multidisciplinary approach involving biochemical, immunochemical, genetic, cell biological and population based studies.We were one of the initiators and significant contributors to the malaria genome project that is now nearing completion.