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Examining the impact arrhythmic gene expression has on fitness in cyanobacteria possessing a complete circadian clock

Award Number: F32GM130070
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

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ABSTRACT Circadian rhythms controlled by intrinsic biological clocks enable anticipatory changes in cellular physiology to promote adaptation to daily environmental cycles. The pervasiveness of circadian programs among eukaryotes and cyanobacteria suggests that circadian clocks confer a fitness advantage to organisms exposed to fluctuating growth environments. Despite the ubiquity of circadian clocks, the specific benefits of circadian systems to overall fitness have remained elusive. Previous studies in the model cyanobacterium Synechococcus elongatus PCC 7942 demonstrated that cyanobacteria whose circadian period closely matches the external light cycle are more fit than strains with periods that differ. Importantly, these studies relied on mutants with defective core clocks, which resulted in previously unappreciated pleiotropic consequences. Here, we propose to test the fitness benefit of circadian rhythms in cyanobacteria using a strain that is unable to produce oscillations in gene expression despite possessing an intact circadian clock, in order to avoid biases encountered by clock mutants. The previously described crm1 mutant contains a transposon insertion in the crm (circadian rhythmicity modulator) ORF that results in arrhythmic expression of clock controlled genes. The crm1 allele elicits phenotypes distinct from arrhythmic kaiC-null and rpaA-null strains, and the crm1 mutant grows in alternating light-dark cycles, providing a strain with moderate arrhythmic gene expression ideal for fitness studies. Competition experiments between the arrhythmic crm1 mutant and WT or other arrhythmic mutants, coupled with metabolic profiles and high-throughput TnSeq-based genetic interaction screens in the crm1 background, will improve our understanding of the fitness consequences encountered by cyanobacteria that fail to maintain rhythmic gene expression. Furthermore, this work is intended to characterize the RpaA-modulating activity of the enigmatic Crm peptide, adding to our model of factors that influence clock output. Taken together, this work has the potential to inform future studies regarding clock-controlled fitness in humans. It is becoming increasingly apparent that the toll of modern life – including shiftwork, blue-light exposure, jet travel and other behaviors – can profoundly disrupt circadian programs in a variety of mammalian tissues, contributing to disease. Our ability to assess the fitness advantage of biological clocks in mammalian tissues is limited, necessitating tractable model organisms such as S. elongatus to investigate fitness components of the clock network. The work may provide a framework for future understanding and treatment of circadian disruption in humans.


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: 2022 ( Subtotal = -$1,815 )
2022	2020	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Biomedical Research and Research Training	002	3	4/22/2022	NON-COMPETING CONTINUATION	-$1,815
2022	2019	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Biomedical Research and Research Training	001	2	4/22/2022	NON-COMPETING CONTINUATION	$0
2022	2018	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Biomedical Research and Research Training	000	1	4/22/2022	NEW	$0
														Subtotal = -$1,815

Issue Date FY: 2021 ( Subtotal = -$55,335 )
2021	2020	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Biomedical Research and Research Training	000	3	10/21/2020	NON-COMPETING CONTINUATION	-$55,335
														Subtotal = -$55,335

Issue Date FY: 2020 ( Subtotal = $65,310 )
2020	2020	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Biomedical Research and Research Training	000	3	8/26/2020	NON-COMPETING CONTINUATION	$65,310
														Subtotal = $65,310

Issue Date FY: 2019 ( Subtotal = $61,226 )
2019	2019	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR DEPT 621	LA JOLLA	CA	92093	SAN DIEGO	USA	Biomedical Research and Research Training	000	2	9/13/2019	NON-COMPETING CONTINUATION	$61,226
														Subtotal = $61,226

Issue Date FY: 2018 ( Subtotal = $58,282 )
2018	2018	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR DEPT 621	LA JOLLA	CA	92093	SAN DIEGO	USA	Biomedical Research and Research Training	000	1	9/5/2018	NEW	$58,282
														Subtotal = $58,282

Grand Total All Awards = $127,668

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Examining the impact arrhythmic gene expression has on fitness in cyanobacteria possessing a complete circadian clock

Award Number: F32GM130070

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

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