TylerU16SF1 Understanding diversification and selection in the emergence of new strains of Cryptosporidium

Cryptosporidium parvum is a cosmopolitan parasite and zoonosis. It is one of the major causes of mortality in children in the developing world, but has a world-wide distribution with outbreaks causing economic loss associated illness to humans and large and small ruminant livestock alike. In recent years we have looked closely into the evolutionary processes and genetic changes associated with host adaptation. Our team have pioneered methods which have produced and analysed the first genomes for clinical isolates which has provided insight into how, when and why new host adapted species have diverged and spread. We identified convergent evolution where strains of C. parvum have adapted to different host species via genetic introgression into a small number of key loci. This highlights: (1) that the enormous evolutionary potential of this pathogen can be rapidly realised by genetic exchange in just a limited number of key loci, and (2) that particular ecological and environmental conditions are required to enable such genetic exchange to take place. Further we have identified the key virulence factors which vary in apparent response to the availability of hosts. Formal test of the significance of these factors requires transgenic parasites. In the last year this has become possible with the publication of culture and transfection protocols. The student selected for this project will develop these techniques in the laboratory in order to prepare transgenic parasites with altered specificity for host.

Objectives of this PhD

1) To improve our understanding of the epidemiology, ecology and evolutionary genetics of Cryptosporidium by quantifying generation times, mutation and recombination rates, selection coefficients, and genetic diversity in single and mixed infections, and identify genes and genetic variants associated with host adaptation through comparative genomics.
2) To culture and transfect cryptosporidium with fluorescent tagged constructs of key virulence factors