Coordinated protein synthesis and degradation during neonatal heart regeneration
About This Grant
Project Summary Mammalian neonatal hearts have the ability to regenerate after ischemic injury, a capacity lost in adulthood. Understanding the mechanisms underlying the regenerative ability of neonatal cardiomyocytes (CMs) could offer critical insights into strategies for repairing injured adult hearts. Our current understanding of neonatal heart regeneration focuses primarily on transcriptomic regulation, despite proteins are the primary effectors of tissue repair. In this project, we investigate the mechanism that drives proteome remodeling and protein homeostasis maintenance during neonatal heart regeneration, which will provide insights into how neonatal CMs rapidly adapt to injury stress and balance protein anabolic and catabolic processes for self-renewal. We observed an acute increase in newly synthesized proteins and enhanced proteasomal activity in regenerative neonatal hearts post-myocardial infarction (MI), which is a response absent in non-regenerative hearts. While protein synthesis and degradation are crucial for tissue growth, the mechanisms that coordinate these processes to maintain protein homeostasis during tissue regeneration and how they are activated by injury remain largely unknown. Our preliminary data indicate that mTORC1 activation in regenerative mouse CMs drives increased protein synthesis following MI and is essential for neonatal heart regeneration. While mTORC1 is known to suppress autophagy, our findings suggest it also promotes protein degradation by regulating Nrf1, an ER-bound transcription factor that controls proteasomal gene expression. Our previous studies showed that Nrf1 is required for neonatal heart regeneration by regulating proteasome activity to mitigate proteolytic stress during injury. We hypothesize that the mTORC1-Nrf1 regulatory axis is activated in neonatal regenerative CMs to enhance both protein synthesis and degradation, promoting critical proteostasis and proteome remodeling during heart regeneration. In Aim 1, we test the hypothesis that mTORC1 activation is a prerequisite for the regenerative response of neonatal CMs after MI by driving rapid translatome remodeling during heart regeneration. Aim 1 also studies how amino acid metabolism, particularly through the LAT1 transporter, which is highly activated in neonatal CMs post-MI, contributes to regenerative mTORC1 activation. Aim 2 investigates the role of the mTORC1-Nrf1 axis in protein homeostasis and proteome remodeling during heart regeneration and examines the function of the proteasome in maintaining proteostasis and supporting heart regeneration. Aim 2 also investigates whether activating the mTORC1-Nrf1 axis can benefit adult heart repair. This proposal will provide important insights into heart regeneration by revealing the role of the mTORC1–Nrf1 axis in regulating protein homeostasis and proteome remodeling during neonatal heart regeneration, which has been overlooked by previous transcriptomic-focused studies.
Grant Summary
Coordinated protein synthesis and degradation during neonatal heart regeneration is a NHLBI - National Heart Lung and Blood Institute grant providing up to $866K for university, nonprofit, healthcare org. Applications are due 2031-01-31 (open). Check eligibility and apply with FindGrants.
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How to Apply
Up to $866K
2031-01-31
- 1Confirm your organization is eligible for Coordinated protein synthesis and degradation during neonatal heart regeneration from NHLBI - National Heart Lung and Blood Institute, 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.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NHLBI - National Heart Lung and Blood Institute before the deadline.
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Coordinated protein synthesis and degradation during neonatal heart regeneration: Frequently Asked Questions
Who is eligible for the Coordinated protein synthesis and degradation during neonatal heart regeneration?
Coordinated protein synthesis and degradation during neonatal heart regeneration is offered by NHLBI - National Heart Lung and Blood Institute 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 Coordinated protein synthesis and degradation during neonatal heart regeneration provide?
Coordinated protein synthesis and degradation during neonatal heart regeneration provides up to $866K per award from NHLBI - National Heart Lung and Blood Institute. 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 Coordinated protein synthesis and degradation during neonatal heart regeneration deadline?
Applications for Coordinated protein synthesis and degradation during neonatal heart regeneration are due 2031-01-31 (open). Because deadlines can change, verify the date with the funder, NHLBI - National Heart Lung and Blood Institute, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Coordinated protein synthesis and degradation during neonatal heart regeneration?
To apply for Coordinated protein synthesis and degradation during neonatal heart regeneration, 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 NHLBI - National Heart Lung and Blood Institute.