Improving accessibility and efficacy of in vivo forward genetic screening
Active Project Grant Awarded Last action
- Award ID
- R35GM156990
- Recipient
-
Trustees Of Indiana University UEI SHHBRBAPSM35
- Awarding agency
-
National Institute of General Medical Sciences
National Institutes of Health, Department of Health and Human Services
- Obligated
- $1,163,669
Award facts
- Assistance listing
- 93.859 Biomedical Research and Research Training
- Completion date 24% complete
- Originally
- Place of performance
- Indianapolis, IN 46202, USA
Award details come from USAspending.gov.
Description
- Abstract
- The advent of fast and affordable sequencing technologies has facilitated detailed descriptive annotation of many mammalian genomes. In contrast, functional annotation connecting genetic variants to phenotypes is severely lacking, due to an inability to conduct current methods at scale. Removing this bottleneck will facilitate rapid identification and characterization of key regulators of physiological and disease processes, which is necessary for the development of targeted therapeutics. Methodologies based on high-throughput functional genomics offer a rapid, affordable, and systematic way to characterize gene functions, with crispr-based pooled forward genetic screens being one such method, which has been used to great effect in cultured cells. However, due to multiple barriers, the in vivo application of forward genetic screens has thus far been extremely limited, hindering our ability to study tissues that cannot be adequately modeled in vitro, such as the heart and brain. In this work, we assess the obstacles hindering extensive adoption of forward genetic screens in vivo and propose innovative techniques to overcome these challenges. We will utilize the heart for proof-of- concept studies that will examine regulation of nppa, a gene encoding the cardiovascular disease biomarker atrial natriuretic peptide (ANP). Our methodologies can be adapted to many tissues and will provide significant value to diverse research initiatives. Furthermore, we propose a groundbreaking in vivo forward genetic screen for regulators of cellular proliferation - a critical biological process relevant to a wide variety of fields such as cancer biology, development, and tissue regeneration. By merging several cutting-edge technologies, our strategy will enable efficient identification of regulators of cardiomyocyte proliferation. This study, which is currently not possible using conventional screening methods, will serve as a blueprint for employing systematic functional genomics in tissues that are difficult to model in vitro or to deliver molecular components to in vivo. In SUM, successful execution of the strategies described in this proposal will considerably reduce the level of expertise and resources that are required to take advantage of the unbiased systematic nature of in vivo forward genetic screens, leading to the improvements in functional annotation of the genome that are necessary to inform the design of therapeutics.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $391,643 | |
| Amendment | $0 | |
| Amendment | $0 | |
| Amendment | $386,013 | |
| Original award | $386,013 |
Quick answers
Who received award R35GM156990?
R35GM156990 was awarded to Trustees Of Indiana University by National Institute of General Medical Sciences (National Institutes of Health) on September 1, 2025.
How much is award R35GM156990 worth?
$1,163,669 has been obligated on R35GM156990.
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