Targeting the stress response in Angelman syndrome
About This Grant
Abstract. Angelman syndrome is a severe neurodevelopmental disorder caused by the loss of maternal UBE3A, a neuronally imprinted gene that encodes the UBE3A ubiquitin ligase. The loss of UBE3A activity causes the dysregulation of an ensemble of proteins in neurons, but the identity of Angelman syndrome-relevant substrates and the pathways they affect remain poorly understood. The primary goal of the proposed research is to understand the neuronal pathways affected by the loss of UBE3A activity and to leverage this information for therapeutic design. Preliminary proteomics studies identified asparagine synthetase (ASNS) as a substrate of UBE3A. ASNS is best studied for its induced expression during the integrated stress response (ISR), an emerging pathway that is dysregulated in various neurodevelopmental disorders. Activation of the ISR suppresses protein synthesis in response to diverse stressors via phosphorylation of the α-subunit of eukaryotic translation initiation factor 2 (p-eIF2α). In human neurons and in brains of Angelman syndrome model mice that lack a copy of maternal Ube3a (Ube3am+/p+), ASNS protein levels are elevated. Moreover, Ube3am+/p+ animals exhibit altered global amino acid levels and increased p-eIF2α levels. Genetic correction of ASNS overabundance improved many behavioral phenotypes and microcephaly, the primary neuroanatomical deficit in Angelman syndrome. Based on these preliminary findings, this proposal aims to: 1) characterize the postnatal targeting of ASNS and ISR in a mouse model of Angelman syndrome, and 2) to characterize the role of ASNS in neuronal development. If successful, this work will provide important therapeutic targets for the treatment of Angelman syndrome and offer new insights for the role of ASNS and the ISR in neuronal development and disease.
Grant Summary
Targeting the stress response in Angelman syndrome is a NIMH - National Institute of Mental Health grant providing up to $641K for university, nonprofit, healthcare org. Applications are due 2031-05-31 (open). Check eligibility and apply with FindGrants.
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Eligibility
How to Apply
Up to $641K
2031-05-31
- 1Confirm your organization is eligible for Targeting the stress response in Angelman syndrome from NIMH - National Institute of Mental Health, 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 NIMH - National Institute of Mental Health before the deadline.
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Targeting the stress response in Angelman syndrome: Frequently Asked Questions
Who is eligible for the Targeting the stress response in Angelman syndrome?
Targeting the stress response in Angelman syndrome is offered by NIMH - National Institute of Mental Health 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 Targeting the stress response in Angelman syndrome provide?
Targeting the stress response in Angelman syndrome provides up to $641K per award from NIMH - National Institute of Mental Health. 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 Targeting the stress response in Angelman syndrome deadline?
Applications for Targeting the stress response in Angelman syndrome are due 2031-05-31 (open). Because deadlines can change, verify the date with the funder, NIMH - National Institute of Mental Health, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Targeting the stress response in Angelman syndrome?
To apply for Targeting the stress response in Angelman syndrome, 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 NIMH - National Institute of Mental Health.