Joshua Tan
Graduate Research Prize Winner 2016
After completing my undergraduate studies at Monash University in Malaysia and Australia, I enrolled in the Wellcome Trust 4-year DPhil programme in Infection, Immunology and Translational Medicine.
In this programme, we perform three rotations during the first year and choose one of the three to follow up on for the rest of the DPhil. I spent two enjoyable rotations in Oxford and did the third at the KEMRI-Wellcome Trust Research Programme in Kilifi, which is a town on the coast of Kenya. There I investigated the antibody response of adults living in a malaria-endemic area to the surface of Plasmodium falciparum-infected erythrocytes. This project, which was done under the supervision of Peter Bull and Kevin Marsh, really captured my interest, and I decided to conduct the rest of my DPhil on this topic.
I ended up spending a year in Kilifi and identified several Kenyan adults who made unusual cross-reactive antibody responses against P. falciparum-infected erythrocytes. To investigate this response at the monoclonal antibody level, I moved to the laboratory of Antonio Lanzavecchia at the Institute for Research in Biomedicine in Bellinzona, Switzerland. There, we found that the broad reactivity of these antibodies was mediated by an insertion of a DNA fragment from a gene called LAIR1 (which is located on a different chromosome) into the antibody locus. We also identified the antigens targeted by these antibodies as RIFINs, which are a group of clonally variant proteins expressed on P. falciparum-infected erythrocytes. This represented a novel mechanism of antibody diversification and suggested that the target antigens may be potential malaria vaccine candidates.
I have greatly enjoyed every aspect of this DPhil – the rotation scheme enabled me to try out different laboratory environments before committing to a particular project, and it has been a great learning experience spending some time at different laboratories specializing in different areas of research. I plan to continue my work on malaria as a postdoctoral researcher and see myself in this line of research for many years to come.
Publications
Tan J, Pieper K, Piccoli L, Abdi A, Foglierini M, Geiger R, Tully CM, Jarrossay D, Ndungu FM, Wambua J, Bejon P, Fregni CS, Fernandez-Rodriguez B, Barbieri S, Bianchi S, Marsh K, Thathy V, Corti D, Sallusto F, Bull P,and Lanzavecchia A. 2016. A LAIR1 insertion generates broadly reactive antibodies against malaria variant antigens. Nature 529, 105-109.
Tan J and Bull PC. 2015. Agglutination assays of the Plasmodium falciparum-infected erythrocyte. Methods in Molecular Biology 1325, 115-129.
Tan J and Sattentau QJ. 2013. The HIV-1-containing macrophage compartment: a perfect cellular niche? Trends in Microbiology 21, 405-412.
Tan JHY, Ludeman JP, Wedderburn J, Canals M, Hall P, Butler SJ, Taleski D, Christopoulos A, Hickey MJ, Payne RJ, and Stone MJ. 2013. Tyrosine sulfation of chemokine receptor CCR2 enhances interactions with both monomeric and dimeric forms of the chemokine monocyte chemoattractant protein-1 (MCP-1). Journal of Biological Chemistry 288, 10024-10034.
Tan JHY, Canals M, Ludeman JP, Wedderburn J, Boston C, Butler SJ, Carrick AM, Parody TR, Taleski D, Christopoulos A, Payne RJ, and Stone MJ. 2012. Design and receptor interactions of an obligate dimeric mutant of the chemokine monocyte chemoattractant protein-1 (MCP-1). Journal of Biological Chemistry 287, 14692-14702.