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RNA folding and catalysis at the interface of biophysics and genomics

Award Number: R35GM127064
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2018
PERIOD OF PERFORMANCE END DATE: 04/30/2029

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RNA folding and catalysis at the interface of biophysics and genomics - Abstract The overall vision of the Bevilacqua lab is that human health can be advanced by combining holistic genomic and detailed molecular views of fundamental problems in RNA biology. Over the next five years, the work outlined in this MIRA will advance RNA folding and catalysis under in vivo and in vivo-like conditions using a combination of traditional and high-throughput (HT) experimental and computational approaches, many of which the lab has helped develop. There will be a balance of development of fundamental methods and new technologies with their application. The molecular perspective employs both traditional biophysical and biochemical approaches, while the holistic perspective uses next-generation sequencing (NGS) approaches. A major goal of this MIRA proposal is to connect these two approaches to discover novel RNA structures and functions and to understand them from both gene regulatory and molecular perspectives. This proposal brings multiple high-throughput (HT) approaches to bear including experimental approaches such as fluorescence-detected binding isotherms (FDBI), massively parallel oligonucleotide synthesis (MPOS), and Structure-seq NGS, as well as computational approaches ranging from cheminformatics to bioinformatics. Goals for the next five years encompass probing RNA folding under biological conditions that include deriving an expanded set of nearest neighbor (NN) parameters for describing RNA folding in the presence of bacterial and human metabolite mixtures. The lab will also explore the dynamics of RNA folding in such in vivo-like conditions using time-resolved studies such as fluorescence-detected stopped-flow kinetics, as well as temperature-dependent probing of RNA structure in vivo to uncover cases where only a fraction of the RNA molecules form a given pairing. Additional efforts will focus on discovery of and novel functions for ribozymes including tolerance of mutation, metabolite assistance of cleavage, occurrence of zymogens (‘ribozymogens’) and their activation, ribozymes being split across exons (‘split ribozymes’), multiple turnover ribozymes, and pseudoribozymes (loss-of-function ribozymes) and their function. Another goal will be to identify unusual charged and tautomeric forms of the nucleobases using a combination of cheminformatics and NGS approaches and to target these with therapeutics. The balance of traditional mechanistic characterization and NGS approaches, as well as the widespread development and application of HT methods, provides an ideal pathway for discovery of and insight into novel RNA biology.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $478,959 )
2025	2025	THE PENNSYLVANIA STATE UNIVERSITY	201 OLD MAIN	UNIVERSITY PARK	PA	16802	CENTRE	USA	Biomedical Research and Research Training	003	7	4/15/2025	NON-COMPETING CONTINUATION	$478,959
2025	2024	THE PENNSYLVANIA STATE UNIVERSITY	201 OLD MAIN	UNIVERSITY PARK	PA	16802	CENTRE	USA	Biomedical Research and Research Training	002	6	2/18/2025	COMPETING CONTINUATION	$0
2025	2024	THE PENNSYLVANIA STATE UNIVERSITY	201 OLD MAIN	UNIVERSITY PARK	PA	16802	CENTRE	USA	Biomedical Research and Research Training	000	6	11/6/2024	COMPETING CONTINUATION	$0
2025	2022	THE PENNSYLVANIA STATE UNIVERSITY	201 OLD MAIN	UNIVERSITY PARK	PA	16802	CENTRE	USA	Biomedical Research and Research Training	001	5	2/18/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $478,959

Issue Date FY: 2024 ( Subtotal = $478,959 )
2024	2024	THE PENNSYLVANIA STATE UNIVERSITY	201 OLD MAIN	UNIVERSITY PARK	PA	16802	CENTRE	USA	Biomedical Research and Research Training	000	6	3/26/2024	COMPETING CONTINUATION	$478,959
														Subtotal = $478,959

Issue Date FY: 2022 ( Subtotal = $381,333 )
2022	2022	PENNSYLVANIA STATE UNIVERSITY, THE	201 OLD MAIN	UNIVERSITY PARK	PA	16802	CENTRE	USA	Biomedical Research and Research Training	000	5	4/7/2022	NON-COMPETING CONTINUATION	$343,200
2022	2022	PENNSYLVANIA STATE UNIVERSITY, THE	201 OLD MAIN	UNIVERSITY PARK	PA	16802	CENTRE	USA	Biomedical Research and Research Training	001	5	6/27/2022	NON-COMPETING CONTINUATION	$38,133
														Subtotal = $381,333

Issue Date FY: 2021 ( Subtotal = $381,333 )
2021	2021	PENNSYLVANIA STATE UNIVERSITY, THE	201 OLD MAIN	UNIVERSITY PARK	PA	16802	CENTRE	USA	Biomedical Research and Research Training	000	4	4/16/2021	NON-COMPETING CONTINUATION	$381,333
														Subtotal = $381,333

Issue Date FY: 2020 ( Subtotal = $388,938 )
2020	2020	PENNSYLVANIA STATE UNIVERSITY, THE	201 OLD MAIN	UNIVERSITY PARK	PA	16802	CENTRE	USA	Biomedical Research and Research Training	000	3	4/9/2020	NON-COMPETING CONTINUATION	$381,333
2020	2020	PENNSYLVANIA STATE UNIVERSITY, THE	201 OLD MAIN	UNIVERSITY PARK	PA	16802	CENTRE	USA	Biomedical Research and Research Training	001	3	6/2/2020	SUPPLEMENT FOR EXPANSION	$7,605
														Subtotal = $388,938

Issue Date FY: 2019 ( Subtotal = $373,159 )
2019	2019	PENNSYLVANIA STATE UNIVERSITY, THE	201 OLD MAIN	UNIVERSITY PARK	PA	16802	CENTRE	USA	Biomedical Research and Research Training	000	2	5/1/2019	NON-COMPETING CONTINUATION	$373,159
														Subtotal = $373,159

Issue Date FY: 2018 ( Subtotal = $458,859 )
2018	2018	PENNSYLVANIA STATE UNIVERSITY, THE	201 OLD MAIN	UNIVERSITY PARK	PA	16802	CENTRE	USA	Biomedical Research and Research Training	001	1	5/10/2018	NEW	$3,739
2018	2018	PENNSYLVANIA STATE UNIVERSITY, THE	201 OLD MAIN	UNIVERSITY PARK	PA	16802	CENTRE	USA	Biomedical Research and Research Training	002	1	8/28/2018	SUPPLEMENT FOR EXPANSION	$79,960
2018	2018	PENNSYLVANIA STATE UNIVERSITY, THE	201 OLD MAIN	UNIVERSITY PARK	PA	16802	CENTRE	USA	Biomedical Research and Research Training	000	1	4/26/2018	NEW	$375,160
														Subtotal = $458,859

Grand Total All Awards = $2,941,540

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RNA folding and catalysis at the interface of biophysics and genomics

Award Number: R35GM127064

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 05/01/2018

PERIOD OF PERFORMANCE END DATE: 04/30/2029

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