| NSF Org: |
MCB Division of Molecular and Cellular Biosciences |
| Recipient: |
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| Initial Amendment Date: | April 15, 2020 |
| Latest Amendment Date: | April 24, 2023 |
| Award Number: | 2027611 |
| Award Instrument: | Standard Grant |
| Program Manager: |
Stephen DiFazio
sdifazio@nsf.gov (703)292-4517 MCB Division of Molecular and Cellular Biosciences BIO Directorate for Biological Sciences |
| Start Date: | May 1, 2020 |
| End Date: | April 30, 2024 (Estimated) |
| Total Intended Award Amount: | $188,253.00 |
| Total Awarded Amount to Date: | $188,253.00 |
| Funds Obligated to Date: |
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| History of Investigator: |
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| Recipient Sponsored Research Office: |
303 COOPER ST CAMDEN NJ US 08102-1519 (856)225-2949 |
| Sponsor Congressional District: |
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| Primary Place of Performance: |
315 Penn St Camden NJ US 08102-1400 |
| Primary Place of
Performance Congressional District: |
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| Unique Entity Identifier (UEI): |
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| Parent UEI: |
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| NSF Program(s): | COVID-19 Research |
| Primary Program Source: |
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| Program Reference Code(s): |
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| Program Element Code(s): |
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| Award Agency Code: | 4900 |
| Fund Agency Code: | 4900 |
| Assistance Listing Number(s): | 47.074 |
ABSTRACT
A novel coronavirus (SARS-CoV-2) emerged in Hubei, China in December 2019 and has since spread rapidly to become a global pandemic. There is a critical need for fundamental research on the biology of this virus and its interactions with the human host to stem the spread of the disease and mitigate its devastating impacts on the global human population. The research supported through this RAPID award will enhance knowledge of how this virus evolves, and it may provide vital clues about its interactions with the human host. Previous research has shown that a critical region of the viral genome is highly conserved, harboring very few mutations compared to the rest of the genome. Exploring the underlying basis for this sequence conservation will reveal new information on factors that could influence the spread, diagnostics and treatment of SARS-CoV-2. The project also offers training opportunities for graduate and undergraduate students, and will support development of a web-based tool for the community to study viral genome evolution.
The PI has identified a region of the SARS-Cov-2 genome, which includes the RNA-dependent RNA polymerase (RdRp), which has extremely high conservation at the nucleotide level. This finding suggests that selection is acting to maintain sequence motifs in this region, possibly pointing to structural constraints on the RdRp RNA or RNA-mediated interactions between the virus and host. The project will explore a range of hypotheses about selection factors, including noncoding RNAs, RNA secondary structure and RNA binding sites for host proteins, among others, that could account for the sequence conservation. The project will also attempt a study relating these factors to human susceptibility to SARS-CoV-2, if access is gained to patient data on genome variation and corresponding infection severity.
This RAPID award is funded by the Genetic Mechanisms Program in the Division of Molecular and Cellular Biosciences.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
PUBLICATIONS PRODUCED AS A RESULT OF THIS RESEARCH
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PROJECT OUTCOMES REPORT
Disclaimer
This Project Outcomes Report for the General Public is displayed verbatim as submitted by the Principal Investigator (PI) for this award. Any opinions, findings, and conclusions or recommendations expressed in this Report are those of the PI and do not necessarily reflect the views of the National Science Foundation; NSF has not approved or endorsed its content.
Despite a slower than expected start due to the pandemic conditions, we have been able to advance well in two main research directions. In one, we identified multiple novel RNAs across SARS-CoV-2 genomes in many patient samples, showing consistent patterns. Such patterns appear to change between variants of concern, revealing novel mechanisms in the virus life cycle.
In the other, we have progressed with the idea that interactions of regulatory RNA with protein-coding genes at specific sites may be a selective factor of sequence conservation. We observed the connection of both research directions as evolutionary traces in the sequenced SARS-CoV-2 genomes, such as deletions/avoidance of some of these sites.
We have produced a publicly available database that presents levels of conservation across different regions and potential factors affecting such conservation in the context of SARS-CoV-2 genome features (coding sequences, RNA structures, potential binding sites, etc.).
We have produced two other publicly available databases, presenting targets of regulatory RNA fragment. They allow users to query a regulatory RNA fragment to find its target and build a focused hypothesis that can be validated experimentally.
The society has been shaken by the pandemic. In addition to helping in developing new vaccines and antiviral drugs, the results could be useful in educating the general public about different aspects of confronting a viral pandemic. The educational component is also very visible in the courses developed during the award period, such as "Coronavirus" and "Biology of Disease".
Over the whole period, 14 undergraduate and graduate students and three high school students have been involved in this research and some 30 students have taken the courses. The number of students participating in research in the lab continues to steadily grow and based on this experience many of them are likely to consider research or medical careers.
Last Modified: 08/15/2024
Modified by: Andrey Grigoriev
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