Defining the mechanisms underlying generational memory inheritance
NINDS - National Institute of Neurological Disorders and Stroke
About This Grant
Project Summary/Abstract Daily light:dark cycles are ubiquitous and regulate most biological functions. Changes in these cycles, such as exposure to artificial light at night or irregular cycles, contribute to deleterious health consequences including increased risk for cancer and cognitive disorders. On a cellular level, excessive/mistimed light can cause morphological changes to hippocampal neurons and molecular changes to neurotransmission. However, mechanistic insights are limited, and these studies focus only on intragenerational consequences. Our recent work has found that constant light or chronic jet lag light impairs associative memory in Drosophila, and this behavior is inherited in three generations of progeny that are reared in standard light:dark. We find that constant light increases PIWI (component of the piRNA pathway) expression in the germline across generations and dampens activity of the Dopamine 1 Receptor, Dop1R1, in the brain. We find that the germline is essential for associative memory, knock down of piwi in constant light in the germline or brain restores memory performance, and in piwi mutants Dop1R1 activity is restored, suggesting that germline to brain epigenetic mechanisms mediate LL-induced impaired memory across generations. This proposal investigates the mechanisms by which irregular light exposure impairs memory via epigenetic changes that impact neural circuits, germline-to-brain signaling and neurotransmitters over generations. I propose to use the genetically tractable Drosophila model to address these mechanisms. Based on my preliminary data, I hypothesize that the PIWI-interacting RNA pathway and H3K9me3 chromatin marks in dopaminergic neurons are responsible for the inheritance of impaired memory (Aim 1). Learning and memory is executed by the action of mushroom body output neurons in the brain. I will identify the memory-relevant mushroom body output neuron whose function is disrupted by constant light (Aim 2). Further, I will interrogate the relationship between the germline and neurons that mediates impaired memory (Aim 3). Finally, I will uncover the role that co-neurotransmitters play in modulating these outcomes (Aim 4). This project combines advanced tools in neurogenetics, epigenomics (CUT&RUN Sequencing), in vivo imaging (fixed-confocal and two-photon live imaging), and behavioral assays to provide novel insights into the mechanisms by which light disruption impairs cognitive function and transmits these effects across generations. Successful completion of this project will have broad implications for understanding how modern light environments impair memory, and how such consequences are inherited. Understanding the effects of irregular light, which plague modern society, is essential for developing interventions to improve human health.
Grant Summary
Defining the mechanisms underlying generational memory inheritance is a NINDS - National Institute of Neurological Disorders and Stroke grant providing up to $128K for university, nonprofit, healthcare org. Applications are due 2028-06-30 (open). Check eligibility and apply with FindGrants.
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Up to $128K
2028-06-30
- 1Confirm your organization is eligible for Defining the mechanisms underlying generational memory inheritance from NINDS - National Institute of Neurological Disorders and Stroke, 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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Defining the mechanisms underlying generational memory inheritance: Frequently Asked Questions
Who is eligible for the Defining the mechanisms underlying generational memory inheritance?
Defining the mechanisms underlying generational memory inheritance is offered by NINDS - National Institute of Neurological Disorders and Stroke 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 mechanisms underlying generational memory inheritance provide?
Defining the mechanisms underlying generational memory inheritance provides up to $128K per award from NINDS - National Institute of Neurological Disorders and Stroke. 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 mechanisms underlying generational memory inheritance deadline?
Applications for Defining the mechanisms underlying generational memory inheritance are due 2028-06-30 (open). Because deadlines can change, verify the date with the funder, NINDS - National Institute of Neurological Disorders and Stroke, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Defining the mechanisms underlying generational memory inheritance?
To apply for Defining the mechanisms underlying generational memory inheritance, 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 NINDS - National Institute of Neurological Disorders and Stroke.