Keith A. Joiner, M.D., co-PI
Yale University School of Medicine

Elisabetta Ullu, Ph.D., co-PI
Yale University School of Medicine

Development of New Genetic Tools to Identify Nutrient Uptake Pathways in Malaria Parasites.

The rapid spreading of Plasmodium falciparum strains that are resistant to current antimalarial therapy has focused the attention of the research community on the urgent need to identify new therapeutic targets, leading to novel therapies. Our laboratories have a long-standing commitment to study nutrient acquisition in Toxoplasma gondii (Keith Joiner), a human pathogen evolutionarily closely related to the malaria parasite, and to develop genetic tools for the human parasite Trypanosoma brucei (Elisabetta Ullu). The objective of our plan is to develop new genetic tools for manipulating the malaria parasite, and use these tools in analysis of nutrient acquisition pathways in P. falciparum-infected erythrocytes. To achieve this goal we will work towards three main objectives. First, we will establish whether parasite genes can be down regulated via gene-specific double-stranded RNA. This is a new paradigm in eukaryotic biology, referred to as RNA interference, which has revolutionized genome-wide analysis of gene function in particular for organisms, such as the malaria parasite, for which the genome sequence is known. Second, we will engineer a bacterial-derived transposon to mutagenize and at the same time tag genes of interest. Thirdly, we will establish methods for identifying and enriching for parasites that are deficient in nutrient uptake. Parasites will be exposed to a variety of exogenous fluorescent markers to specifically label parasite uptake pathways and sorted using FACS. Tracers will be chosen to provide functional data on specific nutrient acquisition pathways, and thus provide invaluable knowledge on the biology of the parasite.

Contact Dr. Ullu.