Malaria continues to kill and debilitate millions of people each year. Plasmodium falciparum, a protozoan parasite responsible for the most severe form of human malaria, is exhibiting a steady loss of sensitivity to standard antimalarial drugs. In some regions of the world, multiple drug resistant strains pose a significant public heath crisis, hence the growing importance in determining the genetic mechanism(s) of drug resistance. To date, most studies addressing drug resistance have neglected the role of transcription in the parasite. The proposed study will test the hypothesis that high resolution transcription profiling will reveal heritable strain-specific variation that map to key regulatory loci. Fluctuations in transcription (e.g. up/down regulation and shifts in expression profiles) and how those fluctuations segregate across a genetic cross will provide us with a window into how the parasite alters components of its natural physiological processes in order to adapt to new environments (e.g. drug exposure). This research will focus on 1) identifyinig strain- specific transcriptional differences in the parents of a genetic cross of P. falciparum in response to antimalarial drug treatment and 2) distinguishing gene expression QTL (eQTL) contributing to regulation of transcriptional variation inherited across the progeny of a genetic cross. ? ? ?
| Gonzales, Joseph M; Patel, Jigar J; Ponmee, Napawan et al. (2008) Regulatory hotspots in the malaria parasite genome dictate transcriptional variation. PLoS Biol 6:e238 |
