Current estimates from the World Health Organization suggest that global cases of infectious disease are rising. Malaria remains a devastating disease in poor and undeveloped countries in Africa, South America and Asia, where nearly one million deaths were reported in 2009. In these areas, parasites can rapidly develop drug resistance, which erodes the efficacy of antimalarials. Thus new drugs and the identification of novel targets are desperately needed to treat malaria. My graduate studies with Prof. Michael Marletta (UC Berkeley) involved detailed mechanistic studies on enzymes that are important to human health. To learn more about infectious disease and chemical biology I joined Prof. Jon Clardy's lab at Harvard Medical School (HMS). At HMS I received training to work with both the blood and liver stages of the malaria parasite. This training allowed me to develop a high-throughput screen to identify inhibitors of liver stage malaria. In the next two years I plan o screen several small molecule libraries for potential therapeutics to treat malaria (Specific Aim 1). During my time at HMS I will also train with several experts to learn how to generate genetic knockouts in malaria, raise drug resistant parasite strains, and maintain transgenic mosquito lines. I can then use this training to evaluate the biological processes of the parasite that my identified liver stage malaria inhibitors target (Specific Aim 2) and to biochemically characterize the protein targets (Specific Aim 3). The training needed to address Specific Aims 2 and 3 will be completed at HMS during the K99 phase of the award, but most of the experiments will be completed during the independent phase of the award. I plan to apply for a tenure-track academic position with the goal of leading a research group focused on characterizing essential processes and proteins of the malaria parasite that facilitate the disease process. HMS is ideally suited for the proposed K99 training period as it has a state-of-the-art high- throughput screening facility and is a leader in infectious disease research with programs like the Harvard Malaria Initiative. I believe the courses and training I receive in the next two years will broaden my understanding of parasite biology and nicely complement my previous skills in enzymology to make me uniquely suited to work on global infectious disease as an independent researcher.

Public Health Relevance

Malaria is a life-threatening disease that is caused by infection from a protozoan parasite. I plan to advance antiparasitic drug discovery and the current understanding of Plasmodium biology by using small molecules to probe for essential parasite processes.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Career Transition Award (K99)
Project #
1K99GM099796-01A1
Application #
8443165
Study Section
Special Emphasis Panel (ZGM1-BRT-X (KR))
Program Officer
Gerratana, Barbara
Project Start
2013-03-01
Project End
2015-02-28
Budget Start
2013-03-01
Budget End
2014-02-28
Support Year
1
Fiscal Year
2013
Total Cost
$89,999
Indirect Cost
$6,667
Name
Harvard University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115
Derbyshire, Emily R; Zuzarte-Luís, Vanessa; Magalhães, Andreia D et al. (2014) Chemical interrogation of the malaria kinome. Chembiochem 15:1920-30
Derbyshire, Emily R; Min, Jaeki; Guiguemde, W Armand et al. (2014) Dihydroquinazolinone inhibitors of proliferation of blood and liver stage malaria parasites. Antimicrob Agents Chemother 58:1516-22