Defining the Role of Histone Lysine Lactylation in Meiosis
NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development
About This Grant
PROJECT SUMMARY Male germ cells produce millions of genetically diverse haploids through meiosis. During meiosis, the activation of meiotic genes plays a pivotal role in expressing the molecular machinery responsible for implementing chromosome synapsis and homologous recombination. The initiation of meiotic recombination involves the programmed formation of DNA double-stranded breaks (DSBs), which preferentially form in permissive chromatin regions marked by H3K4me3 (referred to as “recombination hotspots”). Unlike somatic cells, male germ cells uniquely depend on lactate as their central metabolite. Beyond its role as a metabolite, lactate has recently been shown to induce epigenetic modifications in cells through histone lysine lactylation (Kla), a post- translational modification involving the addition of lactyl groups to lysine residues on histones5. Since lactate levels are often elevated under disease conditions (e.g., produced in the Warburg effect in cancer metabolism), histone Kla has been predominantly studied in the context of various diseases, including cancers, neuropathy, inflammation. Consequently, its physiological functions have remained largely uncharacterized and unreported. Our recent study revealed dynamic histone Kla at histone H4-lysine 5 (K5), -K8, and -K12 during prophase I of mouse spermatogenesis. Thus, we hypothesize that lactate regulates meiotic gene expression and recombination through histone Kla during spermatogenesis. To test this hypothesis, we will: 1) Characterize the role of Slc16a1 during meiosis through histone Kla; 2) Characterize the roles of HBO1 as a lactyl-transferase in germ cells during spermatogenesis. As an R21 Exploratory/Developmental Research Grant Award, our study is expected to establish histone Kla as a novel epigenetic mechanism through which lactate regulates germ cell meiosis. Additionally, it highlights a previously unrecognized role of lactate in the regulation of meiotic gene expression and recombination.
Grant Summary
Defining the Role of Histone Lysine Lactylation in Meiosis is a NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development grant providing up to $426K for university, nonprofit, healthcare org. Applications are due 2028-06-30 (open). Check eligibility and apply with FindGrants.
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Up to $426K
2028-06-30
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Defining the Role of Histone Lysine Lactylation in Meiosis: Frequently Asked Questions
Who is eligible for the Defining the Role of Histone Lysine Lactylation in Meiosis?
Defining the Role of Histone Lysine Lactylation in Meiosis is offered by NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development 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 Defining the Role of Histone Lysine Lactylation in Meiosis provide?
Defining the Role of Histone Lysine Lactylation in Meiosis provides up to $426K per award from NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development. 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 Defining the Role of Histone Lysine Lactylation in Meiosis deadline?
Applications for Defining the Role of Histone Lysine Lactylation in Meiosis are due 2028-06-30 (open). Because deadlines can change, verify the date with the funder, NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development, and give yourself enough time to prepare a complete, competitive application before the close date.
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To apply for Defining the Role of Histone Lysine Lactylation in Meiosis, 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 NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development.