Investigating regulatory mechanisms of in vivo transcriptional dynamics
About This Grant
ABSTRACT Essentially all transcription occurs in stochastic and episodic bursts, conferring flexibility, adaptability, and diversity to otherwise identical cells. Regulating this `bursty' transcription in a timely and context-appropriate manner is key to proper development and homeostasis. Its misregulation causes an imbalance between dynamically counteracting genes and improper gene dosage compensation, often leading to various human diseases, including cancer, cardiovascular disease, metastasis, and infertility. However, molecular mechanisms underlying transcriptional burst regulation remain elusive due to the lack of proper in vivo models and precise long-term assays. Also, the results from previous studies often conflict with each other, hampering our precise understanding and therapeutic advancements. Our overarching goal is to elucidate the molecular mechanisms underpinning spatiotemporal regulation of in vivo transcriptional bursting during development, homeostasis, and disease, and discover new factors controlling its context-specificity and adaptability. Recent studies, including our work monitoring transcriptional dynamics of endogenous Notch target genes in live adult C. elegans, contradict the previous findings: the burst duration is the major parameter regulated in vivo, whereas burst frequency is the major target of regulation in vitro. What causes these discrepancies? What modulates the burst behaviors in a context-specific manner and how? To address these questions, we will use the C. elegans gonad as an in vivo transcriptional burst study model with our innovative approach, combining long- term single-molecule live RNA imaging, machine learning-based analysis and modeling, and bioinformatics to analyze burst dynamics regulation in vivo. Focusing on the burst dynamics of powerful and well-characterized Notch pathway, we will determine the precise roles of core Notch cis- and trans-regulatory elements (CREs and TREs) like promoters, enhancers, and mediators in transcriptional burst regulation both in in vivo and in vitro contexts. We will also define the novel functions of the transcriptional co-activator LAG-3 (MAML in humans) for context-specific regulation of transcriptional dynamics, focusing on its functions for biocondensate formation and chromatin modifications. Our results will fill the critical gap in knowledge about in vivo transcriptional bursting and greatly advance our understanding of transcriptional regulation and stem cell control, with the potential to discover new therapeutic targets and strategies for Notch-related diseases and infertility.
Grant Summary
Investigating regulatory mechanisms of in vivo transcriptional dynamics is a NIGMS - National Institute of General Medical Sciences grant providing up to $300K for university, nonprofit, healthcare org. Applications are due 2030-12-31 (open). Check eligibility and apply with FindGrants.
Not quite the right fit?
Search 9,000+ open grants, or get matches ranked for your organization — free.
Focus Areas
Eligibility
How to Apply
Up to $300K
2030-12-31
- 1Confirm your organization is eligible for Investigating regulatory mechanisms of in vivo transcriptional dynamics from NIGMS - National Institute of General Medical Sciences, 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 NIGMS - National Institute of General Medical Sciences before the deadline.
Don't want to draft it yourself?
We'll draft the complete application against NIGMS - National Institute of General Medical Sciences's requirements, run a quality review, and email you a submission-ready PDF plus an editable Word doc within 5 business days. Most orders deliver in 24-48 hours. Flat $399, any grant size.
AI Requirement Analysis
Detailed requirements not yet analyzed
Have the NOFO? Paste it below for AI-powered requirement analysis.
Investigating regulatory mechanisms of in vivo transcriptional dynamics: Frequently Asked Questions
Who is eligible for the Investigating regulatory mechanisms of in vivo transcriptional dynamics?
Investigating regulatory mechanisms of in vivo transcriptional dynamics is offered by NIGMS - National Institute of General Medical Sciences 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 Investigating regulatory mechanisms of in vivo transcriptional dynamics provide?
Investigating regulatory mechanisms of in vivo transcriptional dynamics provides up to $300K per award from NIGMS - National Institute of General Medical Sciences. 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 Investigating regulatory mechanisms of in vivo transcriptional dynamics deadline?
Applications for Investigating regulatory mechanisms of in vivo transcriptional dynamics are due 2030-12-31 (open). Because deadlines can change, verify the date with the funder, NIGMS - National Institute of General Medical Sciences, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Investigating regulatory mechanisms of in vivo transcriptional dynamics?
To apply for Investigating regulatory mechanisms of in vivo transcriptional dynamics, 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 NIGMS - National Institute of General Medical Sciences.