Harold Ocholla
University
Malawi-Liverpool-Wellcome Trust Clinical Research Programme.
PhD Title
Genome-wide characterization of Plasmodium falciparum genetic diversity.
Abstract
Genome-wide characterization of P.falciparum genetic diversity plays a central role in characterizing factors involved in pathogenesis, virulence, transmission and drug resistance. This will help to better understand the biology of the parasite and aid in defining drug and vaccine targets. Several leading malaria genomics groups are putting effort into this area. We are also in a pole position to contribute towards defining genome-wide genetic diversity of this parasite and discover SNPs or any other polymorphisms that could potentially affect disease progression in a malaria endemic Chikwawa district of Malawi. My interest is in using longitudinal samples from approximately 1500 children enrolled at 4-48 months in an ongoing ACTia study. We will extract parasite DNA and send to Wellcome Trust Sanger Institute for whole genome sequencing followed by genome-wide analysis of genetic variation. We are anticipating that selective pressure on this parasite population will also result from previous use of Sulfadoxine-Pyrimethamine, large scale use of bed-nets and more recently from indoor residual spraying (IRS).
Specifically my main objectives are to:
1. Characterize genetic diversity of P.falciparum infecting children longitudinally over a 2-3 year period as they develop immunity and present with diverse malaria clinical conditions
2. Examine genetic diversity of the parasite under different selective pressure such as drugs, host immune response, bed-nets and IRS
3. Use genome-wide association analysis to detect candidate genes under selection from host immune response and recent positive selection from drugs
4. Describe population structure in this district