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Senior Scholar Award in Global Infectious Disease
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Keith A.
Joiner,
M.D., co-PI
Yale University School of Medicine
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Elisabetta
Ullu,
Ph.D.
Yale University School of Medicine
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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. Joiner.
Contact
Dr. Ullu.
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