Single-cell epigenome analysis of the alzheimer's disease brain

Ended Project Grant Awarded Last action

Award ID
R44AG079691
Recipient
Awarding agency
Obligated
$1,959,866

Award facts

Assistance listing
93.866 Aging Research
Completion date
Place of performance
San Diego, CA 92121, USA

Award details come from USAspending.gov.

Description

Abstract
Late onset ad (LOAD) is a heterogeneous disease that involves complex interactions between genetic, epigenetic, and environmental risk factors. Genome-wide association studies (GWAS) have identified several thousand sequence variants linked to increased or decreased risk of ad, most of which are noncoding. The current paradigm posits that noncoding variants contribute to disease etiology by perturbing transcriptional regulation in disease-relevant cell types, while environmental risk factors contribute to pathogenesis in part via alterations to the epigenome. However, a lack of maps and tools to explore gene activities and their transcriptional regulation at cellular resolution in the brain has presented a major bottleneck to the functional interpretation of noncoding ad risk variants. In prior work, we applied droplet paired-tag multi-omic profiling of transcription and histone post-translational modification to post-mortem ad and control parietal cortex, demonstrating its capacity to profile cellular epigenetics and transcription from bulk samples. This technology has garnered significant interest through our early-access program. In the proposed study, we will develop a manufacturing quality management system incorporating references and reference measurements for the production of droplet paired-tag kits. We will optimize our protocols specifically on post-mortem ad and healthy brain tissue from hippocampus, white matter, and cerebellum, as well as on peripheral blood; and further optimize droplet paired-tag for application to sorted nuclear populations. We will publish the resulting data as a comprehensive cellular encyclopedia of DNA elements. If successful, the research would catalyze the study of the epigenetics of ad, and enable the widespread application of next-generation multi-omic assays to ad and other neurological diseases.

Transactions

Action Obligated Date
Amendment $964,766
Original award $995,100

Quick answers

Who received award R44AG079691?

R44AG079691 was awarded to Epigenome Technologies, Inc. by National Institute on Aging (National Institutes of Health) on September 30, 2022.

How much is award R44AG079691 worth?

$1,959,866 has been obligated on R44AG079691.

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