Metabolic signaling mechanisms controlling mammalian embryonic patterning
NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development
About This Grant
SUMMARY: Gastrulation is a pivotal event in early development, establishing the body plan and shaping future tissues. Even slight alterations in this process can lead to embryonic or fetal lethality, or developmental defects. While traditionally viewed as a passive energy source, recent studies—including our own—reveal that glucose metabolism instructively regulates development. Our findings in mouse embryos show that co-developing epiblast and mesoderm cells rely on distinct branches of glucose metabolism to drive cell fate transitions and subsequent cell movements. Further, we identified specific metabolic intermediates that are selectively required to instruct distinct developmental outcomes, by modulating FGF/ERK signaling. In this proposal, we will combine multi-omics approaches in mouse embryos, embryo-derived tissue explants and in vitro stem cell-based embryo models to uncover how glucose, as a single nutrient, spatially coordinates signaling networks, protein function, and gene expression to drive lineage-specific fate decisions (Aim 1) and morphogenetic behaviors (Aim 2) by generating distinct metabolic intermediates that regulate ERK signaling during mammalian gastrulation. In Aim 1, we perform cell type-resolved isotope tracing and employ 3D high-resolution two-photon live imaging in transgenic reporter mouse embryos to simultaneously track cellular metabolic states and ERK signaling activity in embryonic domains. Building on our preliminary results, we will test the hypothesis that glycosylation via the Hexosamine Biosynthetic Pathway (HBP) acts as a key metabolic mechanism linking glucose flux to ERK activation during the epiblast-to-mesoderm transition. Using proteomics assays and genetic perturbations, we will determine how HBP-driven glycosylation regulates ERK-dependent mesoderm specification. In Aim 2, guided by our preliminary results, we will establish a direct causal relationship between localized lactate production and ERK functionality in mesodermal migration and subsequent developmental progression. We will analyze how glycolysis-driven lactylation regulates key transcription factor and signaling proteins during mesodermal development, employing integrative genomic, proteomic, and functional analyses. These studies will reveal how spatially regulated glucose metabolism shapes developmental trajectories at the intersection of metabolic and signaling networks. By completion of this study, we expect to discover key metabolic mechanisms that instruct local and global embryo morphogenesis and patterning during gastrulation, and the consequences on early developmental patterning when these processes go awry. The advances will provide insights into how progenitor-level defects induced by metabolite availability may cause pregnancy loss and developmental disorders in humans.
Grant Summary
Metabolic signaling mechanisms controlling mammalian embryonic patterning is a NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development grant providing up to $628K for university, nonprofit, healthcare org. Applications are due 2031-02-28 (open). Check eligibility and apply with FindGrants.
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Up to $628K
2031-02-28
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- 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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Metabolic signaling mechanisms controlling mammalian embryonic patterning: Frequently Asked Questions
Who is eligible for the Metabolic signaling mechanisms controlling mammalian embryonic patterning?
Metabolic signaling mechanisms controlling mammalian embryonic patterning 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 Metabolic signaling mechanisms controlling mammalian embryonic patterning provide?
Metabolic signaling mechanisms controlling mammalian embryonic patterning provides up to $628K 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 Metabolic signaling mechanisms controlling mammalian embryonic patterning deadline?
Applications for Metabolic signaling mechanisms controlling mammalian embryonic patterning are due 2031-02-28 (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.
How do you apply for the Metabolic signaling mechanisms controlling mammalian embryonic patterning?
To apply for Metabolic signaling mechanisms controlling mammalian embryonic patterning, 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.