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Molecular and Neural Mechanisms Regulating Foraging and Food Intake

Award Number: R35GM133698
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: 08/07/2019
PERIOD OF PERFORMANCE END DATE: 08/31/2030

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Molecular and Neural Mechanisms Regulating Foraging and Food Intake - PROJECT SUMMARY Food intake is a finely tuned innate behavior controlled by a complex network of sensory, homeostatic, and hedonic mechanisms. In metabolic diseases such as obesity or eating disorders such as anorexia nervosa, the body's normal perception of food and appetite is altered, leading to overeating and weight gain or reduced appetite and weight loss. Understanding the genetic and neural mechanisms regulating food intake and appetite is essential for developing effective treatments for both conditions. While neural circuits that regulate food intake have been extensively studied in rodent models, the complexity of the mammalian brain makes it challenging to explain the underlying molecular mechanisms and circuit dynamics. The overarching goal of this project is to understand the neurogenetic mechanisms by which the brain communicates with the body to regulate food intake and foraging at the neural and molecular levels. We use a genetically tractable model organism, the fly, Drosophila melanogaster, to study the metabolic-state-dependent regulation of food intake and foraging at the levels of genes, cells, and circuits. Previously, we pioneered in vivo functional imaging methods to record the activity of molecularly defined populations of neurons in the fly brain and the enteric nervous system during food ingestion. We also developed high-resolution behavioral assays to capture the foraging and food intake behaviors of individual flies in real time with high temporal resolution. Using these methods, we showed that flies regulate their food ingestion and foraging behaviors by integrating metabolic state and taste/nutritional information in the brain. We further investigated the mechanisms by which a novel class of interneurons (IN1) regulates sugar ingestion. We demonstrated that IN1 neurons regulate sugar ingestion through their bi- directional communication with the fly gastrointestinal tract. Over the next five years, in this R35 MIRA grant, we aim to reveal the molecular pathways that regulate the activity of IN1 neurons in different metabolic states and determine how they become persistently active during sugar ingestion. We will also identify and characterize the functions of central and peripheral neural circuits that interact with IN1 neurons to regulate food intake, foraging, and other innate behaviors. Functional dissection of IN1 circuitry will lead us to the fundamental principles by which the nervous system regulates foraging and food intake. Additionally, we will characterize the molecular and anatomical architecture of the fly enteric nervous system and the functions of enteric neurons in regulating food ingestion and nutrient preference. Understanding the fundamental neural and molecular mechanisms underlying foraging, food intake, and nutrient sensing in flies will help us uncover conserved pathways and principles that regulate these vital behaviors across different species. Once we discover key neurogenetic mechanisms underlying food intake and foraging, we can search for similar processes in more complex mammalian models and in patients suffering from obesity or eating disorders to develop treatment strategies that intervene in the pathogenesis of these life-threatening diseases.


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 = $400,020 )
2025	2025	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Biomedical Research and Research Training	000	6	8/13/2025	COMPETING CONTINUATION	$400,020
														Subtotal = $400,020

Issue Date FY: 2023 ( Subtotal = $401,350 )
2023	2023	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Biomedical Research and Research Training	000	5	7/14/2023	NON-COMPETING CONTINUATION	$401,350
														Subtotal = $401,350

Issue Date FY: 2022 ( Subtotal = $401,350 )
2022	2022	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Biomedical Research and Research Training	000	4	7/22/2022	NON-COMPETING CONTINUATION	$401,350
														Subtotal = $401,350

Issue Date FY: 2021 ( Subtotal = $501,350 )
2021	2021	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Biomedical Research and Research Training	000	3	7/20/2021	NON-COMPETING CONTINUATION	$401,350
2021	2021	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Biomedical Research and Research Training	001	3	9/6/2021	SUPPLEMENT FOR EXPANSION	$100,000
														Subtotal = $501,350

Issue Date FY: 2020 ( Subtotal = $401,350 )
2020	2020	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Biomedical Research and Research Training	000	2	7/29/2020	NON-COMPETING CONTINUATION	$401,350
														Subtotal = $401,350

Issue Date FY: 2019 ( Subtotal = $400,603 )
2019	2019	CORNELL UNIVERSITY, INC	373 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Biomedical Research and Research Training	000	1	8/7/2019	NEW	$400,603
														Subtotal = $400,603

Grand Total All Awards = $2,506,023

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Molecular and Neural Mechanisms Regulating Foraging and Food Intake

Award Number: R35GM133698

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: 08/07/2019

PERIOD OF PERFORMANCE END DATE: 08/31/2030

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