Biography
Jim's lab works on development of synthetic circuits and protozoan biology. He leads an EPSRC Global Challenges Research Fund programme to build and employ low cost viral diagnostics, using Synthetic Biology techniques. Jim’s lab also takes on foundational work such as generalised codon optimisation, robust switches and counters and big DNA manipulation, as well as maintain a long interest in protozoan biology. Jim is co-Chair of the University of Cambridge Synthetic Biology Strategic Research Initiative, and co-founder of Colorifix, a startup that is developing sustainable textile dyeing processes, based on synthetic biology.
Research
The protozoan phylum Apicomplexa is arguably the most important group of parasitic pathogens responsible for human and animal disease. According to recent WHO figures, malaria (Plasmodium spp.) alone produces global morbidity and mortality figures into the hundreds-of-millions affected people each year. The encephalitis caused by Toxoplasma gondii infection kills an estimated 15-20% of all AIDS patients. Livestock losses and the implementation of control measures for avian coccidiosis (Eimeria spp.), costs the poultry industry millions of pounds annually. Despite decades of effort, there has been little progress in the prevention and treatment of apicomplexan diseases.
We are continuing to generate and employ T. gondii genome sequence information to investigate basic properties of the host-parasite interaction. In collaboration with the Pathogen Sequencing Unit at the Sanger Centre, T. gondii RH (type I lineage) chromosome Ia and Ib has been sequenced and annotated. Whole genome shotgun sequence of the ME49 B7 (type II lineage) isolate has been completed at TIGR. Comparsion of ChrIa between the two strains has revealed that the chromosome is identical. This is a surprising result given the high level of SNP polymorphism on ChrIb between the two strains. This observation is consistent with a prediction in our earlier work that some genes/chromosomal regions/chromosomes must be completely conserved between the type lineages and likely carry information essential for clonal growth/infection between intermediate hosts (1,4). Moreover, it appears as though the relationship between the clonal lineages may be explained by a very few number of crosses between ancestral parents (2). This suggests that a genetic crosses are rare but have been critical to the evolution and global population expansion of toxoplasma.
In anticipation of complete genome sequence for T.gondii, we have initiated a microarray project using cDNA clones from the EST effort (5) to study changes in gene expression during infection and growth within the host cell. In collaboration with the Boothroyd lab at Stanford, this microarray analysis has helped identify a key virulence factor that is secreted direcly into the host cell upon invasion (3). Further investigation into his novel mechanism will allow us a greater understanding of how the parasite modulates the host immune response. It is also possible to monitor host cell changes simultaneously with mouse oligonucleotide based microarrays. In addition, we are using NMR and GC-MS metabolomic data to monitor host cell changes, integrating these data with microarray data. These methods and the data generated represent a major step towards understanding the host-parasite interaction and will has applications ranging from defining genes involved with pathogenesis to investigating drug action in vitro.