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Metal Homeostasis in Yeast

Award Number: R01GM041840
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: 04/01/1989
PERIOD OF PERFORMANCE END DATE: 03/31/2024

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View Award Description

Metal Homeostasis in Yeast - The trace element copper (Cu) is an essential cofactor for critical life processes that include mitochondrial oxidative phosphorylation, iron absorption, reactive oxygen detoxification, peptide hormone biogenesis, connective tissue maturation and cellular signaling. Dietary Cu limitation, defects in the Cu acquisition machinery, or the inability to adapt to Cu deficiency gives rise to pathophysiological states in specific cells and tissues including iron deficiency anemia, neuronal and cognitive dysfunction, connective tissue defects, hypertrophic cardiomyopathy and gestational lethality. Importantly, Cu chelators are used to treat patients with devastating Cu overload disease, and are being developed for use in cancer chemotherapy. While Cu acquisition, and appropriate adaptive responses to Cu limitation are critical for human development and health, we know little about how cells adapt to Cu limitation through increased Cu import or critical regulatory changes. This application details experiments to decipher two fundamentally important gaps in our knowledge of the components involved in Cu acquisition and the mechanisms by which cells adapt to Cu-limitation. We will exploit the powerful fungal model system, Cryptococcus neoformans, which has a strong reliance on Cu- dependent metabolism for its growth, and which has a rich biology of genes whose expression is regulated by Cu-deficiency. First, we will elucidate the role that a new extracellular protein, Bim1, plays in Cu acquisition. We will test the hypothesis that Bim1 serves as an extracellular Cu ligand that functions in concert with the Ctr1-mediated plasma membrane Cu+ import machinery and that Bim1 is critical for cell growth and survival in a naturally occurring Cu-limiting environment. These experiments will validate the first extracellular Cu-ligand in eukaryotic Cu-uptake, filling a gap in our understanding of how organisms acquire this essential trace element. Second, we will decipher how under Cu-limiting conditions, expression of the abundant Sod1 Cu-dependent protein is extinguished, the physiological role this plays in prioritizing Cu to proteins critical for normal growth, and how cells adapt to loss of Sod1 through changes in the localization and synthesis of other proteins via cellular translation reprogramming. Together, these studies will advance new concepts for how cells acquire the essential metal ion Cu, invoke adaptive responses to Cu limitation and regulate these processes for normal cell growth, function and health.


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 = -$9,915 )
2024	2022	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Biomedical Research and Research Training	000	32	9/23/2024	NON-COMPETING CONTINUATION	-$9,915
														Subtotal = -$9,915

Issue Date FY: 2022 ( Subtotal = $315,618 )
2022	2022	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Biomedical Research and Research Training	000	32	3/8/2022	NON-COMPETING CONTINUATION	$284,056
2022	2022	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Biomedical Research and Research Training	001	32	6/9/2022	NON-COMPETING CONTINUATION	$31,562
														Subtotal = $315,618

Issue Date FY: 2021 ( Subtotal = $315,916 )
2021	2021	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Biomedical Research and Research Training	000	31	3/12/2021	NON-COMPETING CONTINUATION	$315,916
														Subtotal = $315,916

Issue Date FY: 2020 ( Subtotal = $316,177 )
2020	2020	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Biomedical Research and Research Training	000	30	3/11/2020	NON-COMPETING CONTINUATION	$316,177
2020	2020	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Biomedical Research and Research Training	001	30	5/28/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $316,177

Issue Date FY: 2019 ( Subtotal = $315,922 )
2019	2019	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Biomedical Research and Research Training	000	29	4/1/2019	COMPETING CONTINUATION	$315,922
2019	2019	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Biomedical Research and Research Training	002	29	7/22/2019	COMPETING CONTINUATION	$152
2019	2017	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Biomedical Research and Research Training	001	28	7/22/2019	NON-COMPETING CONTINUATION	-$152
														Subtotal = $315,922

Issue Date FY: 2017 ( Subtotal = $362,003 )
2017	2017	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Biomedical Research and Research Training	001	28	8/3/2017	NON-COMPETING CONTINUATION	$36,201
2017	2017	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Biomedical Research and Research Training	000	28	3/13/2017	NON-COMPETING CONTINUATION	$325,802
														Subtotal = $362,003

Issue Date FY: 2016 ( Subtotal = $362,003 )
2016	2016	DUKE UNIVERSITY	BOX 104004	DURHAM	NC	27708	DURHAM	USA	Biomedical Research and Research Training	000	27	3/8/2016	NON-COMPETING CONTINUATION	$362,003
														Subtotal = $362,003

Issue Date FY: 2015 ( Subtotal = $360,865 )
2015	2015	DUKE UNIVERSITY	BOX 104004	DURHAM	NC	27708	DURHAM	USA	Biomedical Research and Research Training	000	26	3/25/2015	NON-COMPETING CONTINUATION	$360,865
														Subtotal = $360,865

Issue Date FY: 2014 ( Subtotal = $357,450 )
2014	2014	DUKE UNIVERSITY	BOX 104004	DURHAM	NC	27708	DURHAM	USA	Biomedical Research and Research Training	001	25	4/21/2014	COMPETING CONTINUATION	$357,450
2014	2012	DUKE UNIVERSITY	BOX 104004	DURHAM	NC	27708	DURHAM	USA	Biomedical Research and Research Training	000	24	4/16/2014	NON-COMPETING CONTINUATION	$0
														Subtotal = $357,450

Issue Date FY: 2012 ( Subtotal = $332,548 )
2012	2012	DUKE UNIVERSITY	BOX 104004	DURHAM	NC	27708	DURHAM	USA	Biomedical Research and Research Training	000	24	6/27/2012	NON-COMPETING CONTINUATION	$332,548
														Subtotal = $332,548

Issue Date FY: 2011 ( Subtotal = $332,548 )
2011	2011	DUKE UNIVERSITY	BOX 104004	DURHAM	NC	27708	DURHAM	USA	Biomedical Research and Research Training	000	23	7/1/2011	NON-COMPETING CONTINUATION	$332,548
														Subtotal = $332,548

Issue Date FY: 2010 ( Subtotal = $335,907 )
2010	2010	DUKE UNIVERSITY	BOX 104004	DURHAM	NC	27708	DURHAM	USA	Biomedical Research and Research Training	000	22	6/18/2010	NON-COMPETING CONTINUATION	$335,907
														Subtotal = $335,907

Issue Date FY: 2009 ( Subtotal = $339,300 )
2009	2009	DUKE UNIVERSITY	BOX 104004	DURHAM	NC	27708	DURHAM	USA	Biomedical Research and Research Training	001	21	7/10/2009	COMPETING CONTINUATION	$339,300
2009	2008	DUKE UNIVERSITY	BOX 104004	DURHAM	NC	27708	DURHAM	USA	Biomedical Research and Research Training	000	20	7/10/2009	NON-COMPETING CONTINUATION	$0
														Subtotal = $339,300

Issue Date FY: 2008 ( Subtotal = $318,324 )
2008	2008	DUKE UNIVERSITY	BOX 104004	DURHAM	NC	27708	DURHAM	USA	Biomedical Research and Research Training	000	20	12/3/2007	NON-COMPETING CONTINUATION	$318,324
														Subtotal = $318,324

Issue Date FY: 2007 ( Subtotal = $357,817 )
2007	2007	DUKE UNIVERSITY	BOX 104135	DURHAM	NC	27708	DURHAM	USA	Biomedical Research and Research Training	000	19	12/4/2006	NON-COMPETING CONTINUATION	$357,817
														Subtotal = $357,817

Issue Date FY: 2006 ( Subtotal = $341,378 )
2006	2006	DUKE UNIVERSITY	POST OFFICE BOX 40005	DURHAM	NC	27706	DURHAM	USA	Biomedical Research and Research Training	001	18	9/4/2006	SUPPLEMENT FOR EXPANSION	$13,547
2006	2006	DUKE UNIVERSITY	POST OFFICE BOX 40005	DURHAM	NC	27706	DURHAM	USA	Biomedical Research and Research Training	000	18	12/12/2005	NON-COMPETING CONTINUATION	$327,831
														Subtotal = $341,378

Issue Date FY: 2005 ( Subtotal = $335,720 )
2005	2005	DUKE UNIVERSITY	POST OFFICE BOX 40005	DURHAM	NC	27706	DURHAM	USA	Biomedical Research and Research Training	000	17	12/3/2004	COMPETING CONTINUATION	$335,720
														Subtotal = $335,720

Issue Date FY: 2003 ( Subtotal = $274,711 )
2003	2003	UNIVERSITY OF MICHIGAN	3003 S STATE ST 3089 WOLVERINE	ANN ARBOR	MI	48109	WASHTENAW	USA	Genetics and Developmental Biology Research and Research Training	000	15		NON-COMPETING CONTINUATION	$274,711
														Subtotal = $274,711

Issue Date FY: 2002 ( Subtotal = $274,846 )
2002	2002	UNIVERSITY OF MICHIGAN	3003 S STATE ST 3089 WOLVERINE	ANN ARBOR	MI	48109	WASHTENAW	USA	Genetics and Developmental Biology Research and Research Training	000	14	4/1/2002	NON-COMPETING CONTINUATION	$274,846
														Subtotal = $274,846

Issue Date FY: 2001 ( Subtotal = $275,198 )
2001	2001	UNIVERSITY OF MICHIGAN	3003 S STATE ST 3089 WOLVERINE	ANN ARBOR	MI	48109	WASHTENAW	USA	Genetics and Developmental Biology Research and Research Training	000	13	3/30/2001	NON-COMPETING CONTINUATION	$275,198
														Subtotal = $275,198

Issue Date FY: 2000 ( Subtotal = $276,209 )
2000	2000	Regents of the University of Michigan	3003 S STATE ST 3089 WOLVERINE	ANN ARBOR	MI	48109	WASHTENAW	USA	Genetics and Developmental Biology Research and Research Training	000	12	3/13/2000	COMPETING CONTINUATION	$276,209
														Subtotal = $276,209

Grand Total All Awards = $7,004,444

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Metal Homeostasis in Yeast

Award Number: R01GM041840

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: 04/01/1989

PERIOD OF PERFORMANCE END DATE: 03/31/2024

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