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Administrative Supplement to How the endocytic network mediates specificity of cell signaling

Award Number: R35GM124918
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: 08/15/2017
PERIOD OF PERFORMANCE END DATE: 08/31/2028

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Administrative Supplement to How the endocytic network mediates specificity of cell signaling - Summary Abstract: How the Endocytic Network Mediates Specificity of Cell Signaling Receptor crosstalk – the cooperation between two or more receptors to modulate cell responses – is a key signaling mechanism. It enables cells to generate a large combinatorial repertoire of specific signaling with a limited variety of receptors. Receptor crosstalk plays an essential role in cell physiology. Consequently, dysfunctions in receptor crosstalk are associated with many human diseases, such as infectious diseases (including COVID-19), cancer, and cardiovascular diseases. To understand the physical mechanisms by which signals from different receptors are integrated in crosstalk, studies have exclusively focused on receptor interactions at the plasma membrane. In contrast, how the crosstalk signals are transduced with high fidelity from the plasma membrane to the nucleus is poorly understood and scarcely explored. The overall goal of this research is to establish the functional role of the endocytic network in transducing and regulating receptor crosstalk. During the past 6 years, our group has made pioneering discoveries in support of the central hypothesis that the endocytic network is where extracellular chemical and physical stimuli intertwine to regulate receptor crosstalk. Specifically, we reported a new model in which receptors can crosstalk by forming overlapping interfaces between discrete signaling clusters, challenging the prevailing view that receptors oligomerize to crosstalk. Importantly, such spatially organized interaction between receptors at endosomes and plasma membranes is modulated by extracellular physical cues, and directly regulates cell inflammatory responses. These prior discoveries and the plethora of new approaches we developed for studying endosome functions laid a critical and unique foundation for us to address the knowledge gap: how does the endocytic network mediate receptor crosstalk? We will address how the endocytic network orchestrates chemical cues from receptor crosstalk (Direction 1) and transduces extracellular physical cues to refine the specificity of crosstalk signaling (Direction 2). To address the first direction, we will define the physical mechanisms by which endocytic sorting, collective endosome-organelle interactions, and endosome-specific activation modulate crosstalk signaling originated from the plasma membrane. To address the second direction, we will integrate experiments with computational modeling to determine the feedback loop between the endocytic network and cell-matrix interactions that regulate receptor crosstalk. This project will establish a mechanistic and predictive understanding of how the endocytic network mediates the spatiotemporal specificity of receptor crosstalk and cell signaling in general; a topic that is poorly understood. It will also lower the technical barrier that has impeded research on this topic, by establishing novel quantitative toolsets for dissecting the dynamics and function of the endocytic network on multiple length scales. Ultimately, a better understanding of endosome functions in receptor crosstalk will facilitate the development of new therapeutic strategies for 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 = $39,429 )
2025	2025	TRUSTEES OF INDIANA UNIVERSITY	107 S INDIANA AVE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	003	7	12/30/2024	SUPPLEMENT FOR EXPANSION	$39,429
2025	2024	TRUSTEES OF INDIANA UNIVERSITY	107 S INDIANA AVE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	002	7	11/6/2024	NON-COMPETING CONTINUATION	$0
2025	2023	TRUSTEES OF INDIANA UNIVERSITY	107 S INDIANA AVE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	001	6	10/21/2024	COMPETING CONTINUATION	$38,707
2025	2021	TRUSTEES OF INDIANA UNIVERSITY	107 S INDIANA AVE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	000	5	10/21/2024	NON-COMPETING CONTINUATION	-$38,707
														Subtotal = $39,429

Issue Date FY: 2024 ( Subtotal = $413,205 )
2024	2024	TRUSTEES OF INDIANA UNIVERSITY	107 S INDIANA AVE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	000	7	8/26/2024	NON-COMPETING CONTINUATION	$413,205
														Subtotal = $413,205

Issue Date FY: 2023 ( Subtotal = $510,930 )
2023	2023	TRUSTEES OF INDIANA UNIVERSITY	107 S INDIANA AVE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	001	6	8/22/2023	COMPETING CONTINUATION	$510,930
2023	2021	TRUSTEES OF INDIANA UNIVERSITY	107 S INDIANA AVE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	000	5	5/3/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $510,930

Issue Date FY: 2021 ( Subtotal = $393,750 )
2021	2021	TRUSTEES OF INDIANA UNIVERSITY	107 S INDIANA AVE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	000	5	8/16/2021	NON-COMPETING CONTINUATION	$393,750
														Subtotal = $393,750

Issue Date FY: 2020 ( Subtotal = $393,750 )
2020	2020	TRUSTEES OF INDIANA UNIVERSITY	107 S INDIANA AVENUE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	000	4	5/27/2020	NON-COMPETING CONTINUATION	$393,750
														Subtotal = $393,750

Issue Date FY: 2019 ( Subtotal = $393,750 )
2019	2019	TRUSTEES OF INDIANA UNIVERSITY	BRYAN HALL 107 S INDIANA AVENUE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	000	3	5/29/2019	NON-COMPETING CONTINUATION	$393,750
														Subtotal = $393,750

Issue Date FY: 2018 ( Subtotal = $393,750 )
2018	2018	TRUSTEES OF INDIANA UNIVERSITY	BRYAN HALL 107 S INDIANA AVENUE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	000	2	5/30/2018	NON-COMPETING CONTINUATION	$393,750
														Subtotal = $393,750

Issue Date FY: 2017 ( Subtotal = $393,750 )
2017	2017	TRUSTEES OF INDIANA UNIVERSITY	BRYAN HALL 107 S INDIANA AVENUE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	000	1	8/8/2017	NEW	$393,750
														Subtotal = $393,750

Grand Total All Awards = $2,932,314

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Administrative Supplement to How the endocytic network mediates specificity of cell signaling

Award Number: R35GM124918

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: 08/15/2017

PERIOD OF PERFORMANCE END DATE: 08/31/2028

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