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Molecular and Neural Mechanisms of Temperature Preference Rhythm in Drosophila

Award Number: R01GM107582
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: 09/01/2013
PERIOD OF PERFORMANCE END DATE: 11/30/2023

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Molecular and Neural Mechanisms of Temperature Preference Rhythm in Drosophila - Human body temperature increases during wakefulness and decreases during sleep. The body temperature rhythm (BTR) is a robust output of the circadian clock and is fundamental for maintaining homeostasis, such as generating metabolic energy and sleep, as well as entraining peripheral clocks in mammals. However, the mechanisms that regulate BTR are largely unknown. Therefore, there is a crucial need to identify the molecular mechanisms that regulate BTR. Drosophila are ectotherms, and their body temperatures are close to ambient temperature; therefore, flies select a preferred environmental temperature to set their body temperature. We identified a novel circadian output, the temperature preference rhythm (TPR), in which the preferred temperature in flies increases during the day and decreases at night. TPR thereby produces a daily body temperature rhythm. Fly TPR shares many features with mammalian BTR. During the current grant term, we established that Diuretic hormone 31 receptor (DH31R), a Drosophila calcitonin receptor family protein, mediates TPR, and we demonstrated that the closest mouse homolog of DH31R, calcitonin receptor (Calcr), is essential for normal BTR in mice. Importantly, both TPR and BTR are regulated in a distinct manner from locomotor activity rhythms, and neither DH31R nor Calcr regulate locomotor activity rhythms. Together, our findings suggest that DH31R/Calcr is an ancient and specific mediator of BTR. Thus, understanding fly TPR will provide fundamental insights into the molecular and neural mechanisms that control BTR in mammals. The goal of this proposal is to determine the molecular and neural mechanisms of TPR. Our recent study suggests that DH31 acts on clock neurons via DH31R to regulate TPR. Although DH31 primarily activates DH31R, DH31 can also activate the Pigment dispersing factor receptor (PDFR), required for locomotor activity rhythms, at a modest level in vitro. Because PDFR does not play a major role in daytime TPR, we expect that DH31R and PDFR are expressed in different cells. In addition to the identification of crucial ligand-receptor interactions, we recently found that master clock cells, the dorsal clock neurons 2 (DN2s), control TPR but not locomotor activity rhythms. The central hypothesis of this proposal: DN2s have temporally-regulated contacts with DN1ps and control rhythmic expression of DH31, which activates DH31R in PDFR-negative DN1ps, resulting in TPR. In Aim 1, we will elucidate the physical and functional relationship between DN1ps and DN2s to control TPR. In Aim 2, we will determine the mechanism that sets rhythmic DH31 expression in DN1ps. In Aim 3, we will determine the mechanism by which DH31R-expressing neurons control TPR. This project will contribute to a mechanistic understanding of fly TPR. The outcomes of this study should ultimately provide a novel mechanistic understanding of the mammalian BTR.


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: 2024 ( Subtotal = -$58 )
2024	2022	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR STE 300	DAVIS	CA	95618	YOLO	USA	Biomedical Research and Research Training	000	10	6/6/2024	NON-COMPETING CONTINUATION	$0
2024	2022	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR STE 300	DAVIS	CA	95618	YOLO	USA	Biomedical Research and Research Training	001	10	7/11/2024	NON-COMPETING CONTINUATION	-$58
														Subtotal = -$58

Issue Date FY: 2023 ( Subtotal = $957 )
2023	2021	CHILDRENS HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Biomedical Research and Research Training	000	8	11/23/2022	NON-COMPETING CONTINUATION	$957
														Subtotal = $957

Issue Date FY: 2022 ( Subtotal = $329,700 )
2022	2022	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Biomedical Research and Research Training	000	10	11/25/2021	NON-COMPETING CONTINUATION	$296,730
2022	2022	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Biomedical Research and Research Training	003	10	8/1/2022	NON-COMPETING CONTINUATION	$32,970
2022	2021	CHILDRENS HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Biomedical Research and Research Training	001	8	3/4/2022	NON-COMPETING CONTINUATION	-$43,960
2022	2021	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Biomedical Research and Research Training	002	9	3/4/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$43,960
														Subtotal = $329,700

Issue Date FY: 2021 ( Subtotal = $331,031 )
2021	2021	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Biomedical Research and Research Training	005	9	7/20/2021	SUPPLEMENT FOR EXPANSION	$207,921
2021	2021	CHILDREN'S HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Biomedical Research and Research Training	001	8	2/23/2021	NON-COMPETING CONTINUATION	$33,390
2021	2021	CHILDREN'S HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Biomedical Research and Research Training	002	8	7/19/2021	NON-COMPETING CONTINUATION	-$228,079
2021	2021	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Biomedical Research and Research Training	004	9	7/19/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$225,210
2021	2021	CHILDREN'S HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Biomedical Research and Research Training	000	8	12/2/2020	NON-COMPETING CONTINUATION	$300,510
2021	2020	CHILDREN'S HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Biomedical Research and Research Training	003	7	7/19/2021	SUPPLEMENT FOR EXPANSION	-$207,921
														Subtotal = $331,031

Issue Date FY: 2020 ( Subtotal = $541,821 )
2020	2020	CHILDREN'S HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Biomedical Research and Research Training	001	7	3/10/2020	NON-COMPETING CONTINUATION	$33,390
2020	2020	CHILDREN'S HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Biomedical Research and Research Training	000	7	12/11/2019	NON-COMPETING CONTINUATION	$300,510
2020	2020	CHILDREN'S HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Biomedical Research and Research Training	002	7	6/18/2020	SUPPLEMENT FOR EXPANSION	$207,921
														Subtotal = $541,821

Issue Date FY: 2019 ( Subtotal = $406,087 )
2019	2019	CHILDREN'S HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Biomedical Research and Research Training	004	6	7/10/2019	SUPPLEMENT FOR EXPANSION	$72,187
2019	2019	CHILDREN'S HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Biomedical Research and Research Training	003	6	4/30/2019	COMPETING CONTINUATION	$28,448
2019	2019	CHILDREN'S HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Biomedical Research and Research Training	001	6	1/14/2019	COMPETING CONTINUATION	$333,900
2019	2017	CHILDREN'S HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Biomedical Research and Research Training	000	5	1/9/2019	NON-COMPETING CONTINUATION	$0
2019	2017	CHILDREN'S HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Biomedical Research and Research Training	002	5	4/30/2019	NON-COMPETING CONTINUATION	-$28,448
														Subtotal = $406,087

Issue Date FY: 2017 ( Subtotal = $290,700 )
2017	2017	CHILDREN'S HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Biomedical Research and Research Training	002	5	8/17/2017	NON-COMPETING CONTINUATION	$290,700
2017	2016	CHILDREN'S HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Biomedical Research and Research Training	001	4	12/17/2016	EXTENSION WITH OR WITHOUT FUNDS	$28,448
2017	2015	CHILDREN'S HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Biomedical Research and Research Training	000	3	12/17/2016	NON-COMPETING CONTINUATION	-$28,448
														Subtotal = $290,700

Issue Date FY: 2016 ( Subtotal = $290,700 )
2016	2016	CHILDREN`S HOSPITAL MEDICAL CENTER	3333 BURNET AVENUE	CINCINNATI	OH	45229	HAMILTON	USA	Biomedical Research and Research Training	000	4	9/13/2016	EXTENSION WITH OR WITHOUT FUNDS	$290,700
														Subtotal = $290,700

Issue Date FY: 2015 ( Subtotal = $290,700 )
2015	2015	CHILDREN`S HOSPITAL MEDICAL CENTER	3333 BURNET AVENUE	CINCINNATI	OH	45229	HAMILTON	USA	Biomedical Research and Research Training	000	3	8/21/2015	NON-COMPETING CONTINUATION	$290,700
														Subtotal = $290,700

Issue Date FY: 2014 ( Subtotal = $286,672 )
2014	2014	CHILDREN`S HOSPITAL MEDICAL CENTER	3333 BURNET AVENUE	CINCINNATI	OH	45229	HAMILTON	USA	Biomedical Research and Research Training	000	2	9/1/2014	NON-COMPETING CONTINUATION	$286,672
														Subtotal = $286,672

Issue Date FY: 2013 ( Subtotal = $286,672 )
2013	2013	CHILDREN`S HOSPITAL MEDICAL CENTER	3333 BURNET AVENUE	CINCINNATI	OH	45229	HAMILTON	USA	Biomedical Research and Research Training	000	1	8/19/2013	NEW	$286,672
														Subtotal = $286,672

Grand Total All Awards = $3,054,983

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Molecular and Neural Mechanisms of Temperature Preference Rhythm in Drosophila

Award Number: R01GM107582

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: 09/01/2013

PERIOD OF PERFORMANCE END DATE: 11/30/2023

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