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Investigation into protein quality control pathways in Dictyostelium discoideum

Award Number: R35GM119544
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: 07/15/2016
PERIOD OF PERFORMANCE END DATE: 03/31/2027

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Investigation into protein quality control pathways in Dictyostelium discoideum - Abstract Protein aggregation is a hallmark of at least 71 diseases. Protein aggregates are caused by an imbalance in protein homeostasis resulting in the accumulation of misfolded proteins. One major question in biomedical research is: How do cells recognize and deal with misfolded proteins? My laboratory has taken a unique approach to answering this question. Instead of studying protein aggregation in model organisms where proteins readily aggregate, we have identified Dictyostelium discoideum (Dictyostelium) as a proteostatic outlier, highly resistant to protein aggregation. Using this unique feature of Dictyostelium we are working to identify how nature has dealt with the problem of protein aggregation. Once we determine the mechanisms Dictyostelium utilize to suppress protein aggregation we plan to determine if this information can be used to develop therapeutic strategies. In the next five years our goal is to have a comprehensive analysis of factors that suppress protein aggregation in Dictyostelium. Factors that suppress protein aggregation in Dictyostelium will then be tested to determine if they can be used to treat human diseases caused by protein aggregation. In addition to our work on identifying how Dictyostelium evades protein aggregation we are also interested in what biological role pathways that suppress protein aggregation play in Dictyostelium biology. One particular area of interest is in Dictyostelium’s developmental cycle where single cellular amoeba transition to multicellular fruiting body. This developmental cycle is of interest because the initial gene that we identified as a suppressor of protein aggregation is part of a large gene family found only in Dictyostelium discoideum and Dictyostelium purpureum, two closely related organisms that undergo this developmental process. This gene family is developmentally regulated with most genes being transcribed in short bursts at time points during and after Dictyostelium becomes multicellular. In the coming years we want to understand what role this protein family plays in Dictyostelium development to determine if suppression of protein aggregation plays a critical role in Dictyostelium development.


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: 2026 ( Subtotal = $402,500 )
2026	2026	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Biomedical Research and Research Training	000	11	4/2/2026	NON-COMPETING CONTINUATION	$402,500
														Subtotal = $402,500

Issue Date FY: 2025 ( Subtotal = $402,500 )
2025	2025	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Biomedical Research and Research Training	001	10	4/9/2025	NON-COMPETING CONTINUATION	$402,500
2025	2024	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Biomedical Research and Research Training	000	9	12/23/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $402,500

Issue Date FY: 2024 ( Subtotal = $402,500 )
2024	2024	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Biomedical Research and Research Training	001	9	7/17/2024	NON-COMPETING CONTINUATION	$40,250
2024	2024	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Biomedical Research and Research Training	000	9	3/27/2024	NON-COMPETING CONTINUATION	$362,250
														Subtotal = $402,500

Issue Date FY: 2023 ( Subtotal = $402,500 )
2023	2023	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Biomedical Research and Research Training	000	8	3/21/2023	NON-COMPETING CONTINUATION	$402,500
														Subtotal = $402,500

Issue Date FY: 2022 ( Subtotal = $402,500 )
2022	2022	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Biomedical Research and Research Training	002	7	8/24/2022	COMPETING CONTINUATION	$17
2022	2022	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Biomedical Research and Research Training	000	7	6/23/2022	COMPETING CONTINUATION	$402,500
2022	2020	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Biomedical Research and Research Training	001	6	8/24/2022	NON-COMPETING CONTINUATION	-$17
														Subtotal = $402,500

Issue Date FY: 2020 ( Subtotal = $395,095 )
2020	2020	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Biomedical Research and Research Training	000	6	6/24/2020	NON-COMPETING CONTINUATION	$395,095
														Subtotal = $395,095

Issue Date FY: 2019 ( Subtotal = $403,473 )
2019	2019	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Biomedical Research and Research Training	002	5	7/1/2019	NON-COMPETING CONTINUATION	$395,378
2019	2018	MEDICAL COLLEGE OF WISCONSIN, INC., THE	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Biomedical Research and Research Training	003	3	7/12/2019	SUPPLEMENT FOR EXPANSION	-$17,776
2019	2018	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Biomedical Research and Research Training	004	4	7/12/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$17,776
2019	2018	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Biomedical Research and Research Training	001	4	6/5/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$215,862
2019	2018	MEDICAL COLLEGE OF WISCONSIN, INC., THE	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Biomedical Research and Research Training	000	3	6/5/2019	NON-COMPETING CONTINUATION	-$207,767
														Subtotal = $403,473

Issue Date FY: 2018 ( Subtotal = $511,502 )
2018	2018	MEDICAL COLLEGE OF WISCONSIN, INC., THE	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Biomedical Research and Research Training	001	3	9/19/2018	SUPPLEMENT FOR EXPANSION	$126,502
2018	2018	MEDICAL COLLEGE OF WISCONSIN, INC., THE	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Biomedical Research and Research Training	000	3	6/27/2018	NON-COMPETING CONTINUATION	$385,000
														Subtotal = $511,502

Issue Date FY: 2017 ( Subtotal = $385,000 )
2017	2017	MEDICAL COLLEGE OF WISCONSIN, INC., THE	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Biomedical Research and Research Training	000	2	6/5/2017	NON-COMPETING CONTINUATION	$385,000
														Subtotal = $385,000

Issue Date FY: 2016 ( Subtotal = $385,000 )
2016	2016	MEDICAL COLLEGE OF WISCONSIN, INC	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Biomedical Research and Research Training	000	1	7/15/2016	NEW	$385,000
														Subtotal = $385,000

Grand Total All Awards = $4,092,570

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Investigation into protein quality control pathways in Dictyostelium discoideum

Award Number: R35GM119544

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: 07/15/2016

PERIOD OF PERFORMANCE END DATE: 03/31/2027

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