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Genetics of secretion in yeast

Award Number: R01GM035370
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: 07/01/1985
PERIOD OF PERFORMANCE END DATE: 06/30/2028

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Genetics of secretion in yeast - Project Summary The endoplasmic reticulum (ER) undergoes autophagic degradation in response to the accumulation of aggregated proteins within its lumen or in response to starvation. We have proposed that in yeast, actin assembly at sites of contact between the cortical ER (cER) and endocytic pits is required to displace elements of the cER from their association with the plasma membrane so that they can interact with the autophagosome assembly machinery near the vacuole. To test our model, we will determine if the requirement in cER-phagy for actin assembly at endocytic pits can be bypassed by deleting all six genes encoding ER-plasma membrane tethers (DTether). If the role of actin assembly is to push the cER away from the plasma membrane, the DTether mutations should bypass the need for actin assembly in ER-phagy. We will ask if the bypass of actin assembly is specific to cER-phagy or if actin-related defects in other selective autophagy pathways, such as nucleophagy, mitophagy, and pexophagy are also bypassed. As an additional test we will ask if an artificial ER-plasma membrane tether can block cER- phagy in both wild type and the DTether strain. Extensive parallels between ER-phagy in yeast and mammalian cells suggest a conserved mechanism. A long-term goal will be to use siRNA knock downs of actin assembly components in U2OS cells to assess their roles in ER-phagy. We will order all known cER-phagy requirements with respect to the displacement of the cER from the plasma membrane. Our recent data suggests that a vesicle coat adaptor protein associates with a selective ER-phagy receptor prior to the displacement of cER from the plasma membrane. We will develop a bimolecular fluorescence complementation assay to visualize the dynamics of this ER-phagy intermediate in live cells. We will also order the displacement of the cER from the plasma membrane with respect to the super assembly of Atg40 oligomers, a process required for packaging of ER fragments into autophagosomes. We will explore a novel fluorescence complementation assay for super assembly of Atg40 oligomers that will allow visualization in live cells. In total our studies will define the pathway by which the ER is degraded by autophagy. This pathway plays a key role in a variety of human diseases including neurodegenerative disorders and forms of diabetes.


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 = $465,901 )
2025	2025	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Biomedical Research and Research Training	001	40	6/18/2025	NON-COMPETING CONTINUATION	$465,901
2025	2023	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Biomedical Research and Research Training	000	38	3/20/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $465,901

Issue Date FY: 2024 ( Subtotal = $465,901 )
2024	2024	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Biomedical Research and Research Training	000	39	6/26/2024	COMPETING CONTINUATION	$465,901
														Subtotal = $465,901

Issue Date FY: 2023 ( Subtotal = $452,332 )
2023	2023	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DRIVE	LA JOLLA	CA	92093	SAN DIEGO	USA	Biomedical Research and Research Training	000	38	6/14/2023	NON-COMPETING CONTINUATION	$452,332
														Subtotal = $452,332

Issue Date FY: 2022 ( Subtotal = $472,175 )
2022	2022	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Biomedical Research and Research Training	001	37	6/20/2022	SUPPLEMENT FOR EXPANSION	$19,843
2022	2022	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Biomedical Research and Research Training	000	37	6/10/2022	NON-COMPETING CONTINUATION	$452,332
														Subtotal = $472,175

Issue Date FY: 2021 ( Subtotal = $490,147 )
2021	2021	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Biomedical Research and Research Training	001	36	6/29/2021	NON-COMPETING CONTINUATION	$452,332
2021	2021	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Biomedical Research and Research Training	002	36	9/14/2021	SUPPLEMENT FOR EXPANSION	$37,815
2021	2019	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Biomedical Research and Research Training	000	34	6/12/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $490,147

Issue Date FY: 2020 ( Subtotal = $523,569 )
2020	2020	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Biomedical Research and Research Training	001	35	7/29/2020	COMPETING CONTINUATION	$450,900
2020	2020	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Biomedical Research and Research Training	002	35	9/3/2020	SUPPLEMENT FOR EXPANSION	$72,669
2020	2019	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Biomedical Research and Research Training	000	34	7/21/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $523,569

Issue Date FY: 2019 ( Subtotal = $430,819 )
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	34	1/7/2019	NON-COMPETING CONTINUATION	$430,819
														Subtotal = $430,819

Issue Date FY: 2018 ( Subtotal = $430,819 )
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	33	12/4/2017	NON-COMPETING CONTINUATION	$387,736
2018	2018	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR DEPT 621	LA JOLLA	CA	92093	SAN DIEGO	USA	Biomedical Research and Research Training	001	33	6/18/2018	NON-COMPETING CONTINUATION	$43,083
														Subtotal = $430,819

Issue Date FY: 2017 ( Subtotal = $430,819 )
2017	2017	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR DEPT 621	LA JOLLA	CA	92093	SAN DIEGO	USA	Biomedical Research and Research Training	000	32	12/12/2016	NON-COMPETING CONTINUATION	$387,737
2017	2017	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR DEPT 621	LA JOLLA	CA	92093	SAN DIEGO	USA	Biomedical Research and Research Training	001	32	7/18/2017	NON-COMPETING CONTINUATION	$43,082
														Subtotal = $430,819

Issue Date FY: 2016 ( Subtotal = $430,819 )
2016	2016	UNIVERSITY OF CALIFORNIA-SAN DIEGO	9500 GILMAN DRIVE	LA JOLLA	CA	92093	SAN DIEGO	USA	Biomedical Research and Research Training	000	31	12/11/2015	COMPETING CONTINUATION	$430,819
														Subtotal = $430,819

Issue Date FY: 2015 ( Subtotal = $416,251 )
2015	2015	UNIVERSITY OF CALIFORNIA-SAN DIEGO	9500 GILMAN DRIVE	LA JOLLA	CA	92093	SAN DIEGO	USA	Biomedical Research and Research Training	001	30	2/9/2015	NON-COMPETING CONTINUATION	$41,624
2015	2015	UNIVERSITY OF CALIFORNIA-SAN DIEGO	9500 GILMAN DRIVE	LA JOLLA	CA	92093	SAN DIEGO	USA	Biomedical Research and Research Training	000	30	12/31/2014	NON-COMPETING CONTINUATION	$374,627
														Subtotal = $416,251

Issue Date FY: 2014 ( Subtotal = $416,251 )
2014	2014	UNIVERSITY OF CALIFORNIA-SAN DIEGO	9500 GILMAN DRIVE	LA JOLLA	CA	92093	SAN DIEGO	USA	Biomedical Research and Research Training	001	29	3/20/2014	NON-COMPETING CONTINUATION	$41,624
2014	2014	UNIVERSITY OF CALIFORNIA-SAN DIEGO	9500 GILMAN DRIVE	LA JOLLA	CA	92093	SAN DIEGO	USA	Biomedical Research and Research Training	000	29	12/24/2013	NON-COMPETING CONTINUATION	$374,627
														Subtotal = $416,251

Issue Date FY: 2013 ( Subtotal = $401,683 )
2013	2013	UNIVERSITY OF CALIFORNIA-SAN DIEGO	9500 GILMAN DRIVE	LA JOLLA	CA	92093	SAN DIEGO	USA	Biomedical Research and Research Training	000	28	12/10/2012	NON-COMPETING CONTINUATION	$374,627
2013	2013	UNIVERSITY OF CALIFORNIA-SAN DIEGO	9500 GILMAN DRIVE	LA JOLLA	CA	92093	SAN DIEGO	USA	Biomedical Research and Research Training	001	28	6/13/2013	NON-COMPETING CONTINUATION	$27,056
														Subtotal = $401,683

Issue Date FY: 2012 ( Subtotal = $415,580 )
2012	2012	UNIVERSITY OF CALIFORNIA-SAN DIEGO	9500 GILMAN DRIVE	LA JOLLA	CA	92093	SAN DIEGO	USA	Biomedical Research and Research Training	000	27	12/15/2011	COMPETING CONTINUATION	$415,580
														Subtotal = $415,580

Issue Date FY: 2000 ( Subtotal = $310,303 )
2000	2000	YALE UNIVERSITY	47 College Street	NEW HAVEN	CT	06520	SOUTH CENTRAL CT	USA	Cell Biology and Biophysics Research	000	16	8/3/2000	NON-COMPETING CONTINUATION	$310,303
														Subtotal = $310,303

Issue Date FY: 1999 ( Subtotal = $301,268 )
1999	1999	YALE UNIVERSITY	47 College Street	NEW HAVEN	CT	06520	SOUTH CENTRAL CT	USA	Cell Biology and Biophysics Research	000	15	7/1/1999	NON-COMPETING CONTINUATION	$301,268
														Subtotal = $301,268

Issue Date FY: 1998 ( Subtotal = $339,439 )
1998	1998	YALE UNIVERSITY	47 College Street	NEW HAVEN	CT	06520	SOUTH CENTRAL CT	USA	Cell Biology and Biophysics Research	000	14	8/24/1998	NON-COMPETING CONTINUATION	$339,439
														Subtotal = $339,439

Grand Total All Awards = $7,194,076

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Genetics of secretion in yeast

Award Number: R01GM035370

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: 07/01/1985

PERIOD OF PERFORMANCE END DATE: 06/30/2028

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