Adding spatial resolution and technical improvements to a novel single-cell DNA methylation sequencing technology
About This Grant
ABSTRACT DNA methylation (DNAme) is a core layer of epigenetic regulation with central roles in the establishment and maintenance of cellular identity. Methods to profile DNAme at single-cell resolution are needed to elucidate epigenetic networks governing cell state in healthy tissues and understand their dysregulation in disease and aging. However, existing methods for single-cell methylome profiling are highly inaccessible, and no methods to experimentally profile both DNAme and spatial location currently exist. I have developed a novel method for single-cell DNAme profiling that leverages the widely available 10x Single Cell Multiome and NEB EM-seq kits, which I have named droplet-implemented single-cell DNA methylation sequencing (discDNAme). Applied to nuclei isolated from mouse brain, discDNAme recovered ~3,000 high-quality methylomes that clustered into clearly separated neuronal and non-neuronal subtypes and displayed stereotyped patterns of CpG dinucleotide methylation around key genomic features. However, these measurements lack spatial information on the native tissue contexts of profiled cells, and the protocol’s per-cell library size is lower than current gold-standard methods for measuring single-cell DNAme. I propose (1) development of a spatially resolved single-cell DNA methylation technology by combining discDNAme with slide-tags, a platform for spatially resolved single-nucleus RNA- and/or ATAC-seq developed by our group. To integrate slide-tags with discDNAme, I will develop a protocol in which the “spatial barcode oligos” we use to position nuclei are physically separated from genomic DNA prior to unmethylated cytosine conversion, benchmark this technology in the mouse hippocampus, and apply it to study glioblastoma multiforme. I further propose (2) experiments to improve and benchmark my discDNAme technology. I will systematically test various independent approaches to increase library complexity at different steps of the discDNAme protocol, combine these optimizations into a second-generation protocol, and benchmark this against our original protocol and other leading methods for single-cell DNAme profiling. Completion of this proposal will result in (1) the first high-resolution method to measure spatially resolved single- cell methylomes—a major advancement in spatial omics technologies—and (2) an accessible yet capable tool for single-cell DNAme profiling that will open single-cell DNAme studies to the broader single-cell community.
Grant Summary
Adding spatial resolution and technical improvements to a novel single-cell DNA methylation sequencing technology is a NHGRI - National Human Genome Research Institute grant providing up to $44K for university, nonprofit, healthcare org. Applications are due 2028-01-31 (open). Check eligibility and apply with FindGrants.
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Up to $44K
2028-01-31
- 1Confirm your organization is eligible for Adding spatial resolution and technical improvements to a novel single-cell DNA methylation sequencing technology from NHGRI - National Human Genome Research 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.
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Adding spatial resolution and technical improvements to a novel single-cell DNA methylation sequencing technology: Frequently Asked Questions
Who is eligible for the Adding spatial resolution and technical improvements to a novel single-cell DNA methylation sequencing technology?
Adding spatial resolution and technical improvements to a novel single-cell DNA methylation sequencing technology is offered by NHGRI - National Human Genome Research 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 Adding spatial resolution and technical improvements to a novel single-cell DNA methylation sequencing technology provide?
Adding spatial resolution and technical improvements to a novel single-cell DNA methylation sequencing technology provides up to $44K per award from NHGRI - National Human Genome Research 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 Adding spatial resolution and technical improvements to a novel single-cell DNA methylation sequencing technology deadline?
Applications for Adding spatial resolution and technical improvements to a novel single-cell DNA methylation sequencing technology are due 2028-01-31 (open). Because deadlines can change, verify the date with the funder, NHGRI - National Human Genome Research Institute, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Adding spatial resolution and technical improvements to a novel single-cell DNA methylation sequencing technology?
To apply for Adding spatial resolution and technical improvements to a novel single-cell DNA methylation sequencing technology, 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 NHGRI - National Human Genome Research Institute.