Cellular and molecular profiling of artemisinin-induced persister phenotypes in P. falciparum
NIAID - National Institute of Allergy and Infectious Diseases
About This Grant
ABSTRACT The emergence of resistance to artemisinin drugs is a major impediment to successful treatment of malaria and will be a roadblock for the global goal of eliminating malaria. Unlike other antimalarial drugs, artemisinin drugs act on the early ring stage of development in the erythrocyte. Although the artemisinin drugs reduce parasite biomass rapidly, exposure to dihydroartemisinin also induces a cell cycle arrest known as ring stage dormancy. These dormant forms may persist in circulation for days or even weeks before activating and restarting the asexual development cycle. The mechanism(s) responsible for formation of persisters and their recovery from dormancy are unknown. In this project we will apply two orthologous approaches to discover persister mechanisms in ring stages of Plasmodium falciparum. In Aim 1, we will develop chemical probes for gibberellin (GA3), a phytohormone that we’ve shown induces early release from dormancy. We also will develop probes for fluridone (FLD), an herbicide that inhibits recover from dormancy in artemisinin-induced dormant ring stages. These chemical biology studies, combined with untargeted transcriptomics and metabolomics investigations, will enable us to identify interacting partners for GA3 and FLD that may serve as the basis for persister formation and recovery. We will test the extent to which interacting partners mediate persister formation and recovery using reverse genetics and cellular and biochemical assays. Currently used techniques do not allow for quantitation of the proportion of persisters that form following exposure to drug, remain viable, and their median time to recovery. In Aim 2 will use a novel persister phenotype assay to quantify the rate of persister formation and time at which persisiters recover. We have developed a high content imaging assay that detects individual clones of the parasites and the rate of recovery over time. This assay will be used to develop precise phenotypic data for 104 unique progeny from a genetic cross of a multidrug resistant P. falciparum from Cambodia with a mostly drug- susceptible line from Malawi. From these data we will use quantitative trait loci mapping to identify genes that are associated with the persister and recovery phenotypes. In summary these studies will provide chemical biology and genetics to identify potential mechanism(s) of persister formation and recovery that can enhance our knowledge of artemisinin resistance and serve as targets for new drug discovery efforts.
Grant Summary
Cellular and molecular profiling of artemisinin-induced persister phenotypes in P. falciparum is a NIAID - National Institute of Allergy and Infectious Diseases grant providing up to $437K for university, nonprofit, healthcare org. Applications are due 2028-06-30 (open). Check eligibility and apply with FindGrants.
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Up to $437K
2028-06-30
- 1Confirm your organization is eligible for Cellular and molecular profiling of artemisinin-induced persister phenotypes in P. falciparum from NIAID - National Institute of Allergy and Infectious Diseases, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
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Cellular and molecular profiling of artemisinin-induced persister phenotypes in P. falciparum: Frequently Asked Questions
Who is eligible for the Cellular and molecular profiling of artemisinin-induced persister phenotypes in P. falciparum?
Cellular and molecular profiling of artemisinin-induced persister phenotypes in P. falciparum is offered by NIAID - National Institute of Allergy and Infectious Diseases and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the Cellular and molecular profiling of artemisinin-induced persister phenotypes in P. falciparum provide?
Cellular and molecular profiling of artemisinin-induced persister phenotypes in P. falciparum provides up to $437K per award from NIAID - National Institute of Allergy and Infectious Diseases. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the Cellular and molecular profiling of artemisinin-induced persister phenotypes in P. falciparum deadline?
Applications for Cellular and molecular profiling of artemisinin-induced persister phenotypes in P. falciparum are due 2028-06-30 (open). Because deadlines can change, verify the date with the funder, NIAID - National Institute of Allergy and Infectious Diseases, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Cellular and molecular profiling of artemisinin-induced persister phenotypes in P. falciparum?
To apply for Cellular and molecular profiling of artemisinin-induced persister phenotypes in P. falciparum, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NIAID - National Institute of Allergy and Infectious Diseases.