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Mitochondrial Functions in Malaria Parasites

Award Number: R01AI028398
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/1989
PERIOD OF PERFORMANCE END DATE: 10/31/2028

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Mitochondrial Functions in Malaria Parasites - Project Summary The emergence of eukaryotes from an exclusively prokaryotic biosphere, a momentous event that charted a divergent course for life on Earth, coincided with symbiotic adoption of mitochondria. The complexity of eukaryotes could not have existed and evolved but for the energy economy supported by mitochondrial physiology. Given the strong evidence for the monophyletic origin of mitochondria, it is probable that all extant mitochondria can trace their origin to that singular primordial event at the dawn of eukaryotes. Yet, the evolution has led to tremendous variety of mitochondria, their genomes, their regulation, and their functions, which are as diverse as the organisms they reside in We are interested in understanding mitochondrial functions in malaria parasites, pathogens that extract a tremendous toll from the health and wellbeing of vast multitudes. Over 30 years ago, our group discovered the unusual mtDNA in Plasmodium that encoded just 3 mitochondrial electron transport chain (mtETC) subunits and ribosomal RNA in fragmented and scrambled pieces. With the long-term support of this grant award, we have elucidated many aspects of mitochondrial functions in malaria parasites, showing the organelle to be the target for antimalarial drugs currently in use as well as those in development. We have shown which of the canonical mitochondrial functions are critical in blood stages and which are essential only for the insect stages of the parasite. We have also identified unique and essential features of Plasmodium mitochondrion using genetic and proteomic investigations. In recent years, our efforts have been joined by other investigators working to understand the mitochondrion in apicomplexan parasites. Together, we are at a stage when many of the mysteries surrounding this organelle in Plasmodium and Toxoplasma are being addressed with the application of powerful new approaches. For the next funding period, we are proposing to conduct studies that would bring us closer to answering some of the most critical questions remaining about mitochondrial functions in malaria parasites. These include potential dual function of Complex III, understanding the nature of mitochondrial complexes, and the unusual structural features of mitochondria in asexual and sexual stages of the parasite. As before, the work we are proposing will be carried out by an outstanding collaborative team including a consortium arrangement. Specifically, we will investigate an essential mitochondrial protein an human orthologue of which has been shown to have multiple functions in mitochondrial biogenesis and metabolism. These studies will use biochemical and metabolomic approaches in addition to genetic manipulations. In a consortium arrangement, we will use cryo-electron tomography to study in situ unusual features of mitochondrial structures in asexual and sexual stages of P. falciparum as well as consequences of genetic disruptions of a select number of mitochondrial functions. We will also explore a potential secondary function of the mtETC Complex III as a reason to maintain mtDNA even in mtETC independent parasites.


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 = $581,980 )
2025	2025	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	33	11/6/2024	NON-COMPETING CONTINUATION	$581,980
2025	2024	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	002	32	1/19/2025	COMPETING CONTINUATION	$5
2025	2021	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	001	31	1/19/2025	NON-COMPETING CONTINUATION	-$5
														Subtotal = $581,980

Issue Date FY: 2024 ( Subtotal = $625,728 )
2024	2024	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	001	32	12/22/2023	COMPETING CONTINUATION	$565,729
2024	2024	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	002	32	9/5/2024	COMPETING CONTINUATION	$59,999
2024	2021	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	31	12/14/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $625,728

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2021	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	31	6/2/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $510,184 )
2021	2021	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	31	6/1/2021	NON-COMPETING CONTINUATION	$510,184
														Subtotal = $510,184

Issue Date FY: 2020 ( Subtotal = $510,184 )
2020	2020	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	30	5/13/2020	NON-COMPETING CONTINUATION	$510,184
														Subtotal = $510,184

Issue Date FY: 2019 ( Subtotal = $510,184 )
2019	2019	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	29	5/6/2019	NON-COMPETING CONTINUATION	$510,184
														Subtotal = $510,184

Issue Date FY: 2018 ( Subtotal = $517,730 )
2018	2018	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	001	28	5/25/2018	NON-COMPETING CONTINUATION	$510,184
2018	2017	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	27	3/1/2018	COMPETING CONTINUATION	$7,546
														Subtotal = $517,730

Issue Date FY: 2017 ( Subtotal = $479,962 )
2017	2017	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	002	27	9/26/2017	COMPETING CONTINUATION	$60,481
2017	2017	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	001	27	6/8/2017	COMPETING CONTINUATION	$425,290
2017	2015	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	26	5/25/2017	NON-COMPETING CONTINUATION	-$5,809
														Subtotal = $479,962

Issue Date FY: 2016 ( Subtotal = $0 )
2016	2015	DREXEL UNIVERSITY	3201 ARCH STREET, SUITE 100	PHILADELPHIA	PA	191042875	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	26	7/26/2016	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2015 ( Subtotal = $425,186 )
2015	2015	DREXEL UNIVERSITY	3201 ARCH STREET, SUITE 100	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	26	5/13/2015	NON-COMPETING CONTINUATION	$425,186
														Subtotal = $425,186

Issue Date FY: 2014 ( Subtotal = $425,186 )
2014	2014	DREXEL UNIVERSITY	3201 ARCH STREET, SUITE 100	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	25	5/12/2014	NON-COMPETING CONTINUATION	$425,186
														Subtotal = $425,186

Issue Date FY: 2013 ( Subtotal = $399,675 )
2013	2013	DREXEL UNIVERSITY	3201 ARCH STREET, SUITE 100	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	24	5/24/2013	NON-COMPETING CONTINUATION	$399,675
														Subtotal = $399,675

Issue Date FY: 2012 ( Subtotal = $425,186 )
2012	2012	DREXEL UNIVERSITY	3201 ARCH STREET, SUITE 100	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	23	5/18/2012	NON-COMPETING CONTINUATION	$425,186
														Subtotal = $425,186

Issue Date FY: 2011 ( Subtotal = $425,186 )
2011	2011	DREXEL UNIVERSITY	3201 ARCH STREET, SUITE 100	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	22	5/20/2011	COMPETING CONTINUATION	$425,186
														Subtotal = $425,186

Issue Date FY: 2010 ( Subtotal = $353,636 )
2010	2010	DREXEL UNIVERSITY	3201 ARCH STREET, SUITE 100	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	21	4/30/2010	NON-COMPETING CONTINUATION	$353,636
														Subtotal = $353,636

Issue Date FY: 2009 ( Subtotal = $357,207 )
2009	2009	DREXEL UNIVERSITY	3201 ARCH STREET, SUITE 100	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	20	6/25/2009	NON-COMPETING CONTINUATION	$357,207
														Subtotal = $357,207

Issue Date FY: 2008 ( Subtotal = $357,207 )
2008	2008	DREXEL UNIVERSITY	3201 ARCH STREET, SUITE 100	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	19	5/6/2008	NON-COMPETING CONTINUATION	$357,207
														Subtotal = $357,207

Issue Date FY: 2007 ( Subtotal = $364,125 )
2007	2007	DREXEL UNIVERSITY	3201 ARCH STREET, SUITE 100	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	18	5/22/2007	NON-COMPETING CONTINUATION	$364,125
														Subtotal = $364,125

Issue Date FY: 2006 ( Subtotal = $375,000 )
2006	2006	DREXEL UNIVERSITY	3201 ARCH STREET, SUITE 100	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	17	5/5/2006	COMPETING CONTINUATION	$375,000
														Subtotal = $375,000

Issue Date FY: 2004 ( Subtotal = $463,640 )
2004	2004	DREXEL UNIVERSITY COLLEGE OF MEDICINE	3201 ARCH STREET	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Microbiology and Infectious Diseases Research	001	16	6/17/2004	SUPPLEMENT FOR EXPANSION	$83,640
2004	2004	DREXEL UNIVERSITY COLLEGE OF MEDICINE	3201 ARCH STREET	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Microbiology and Infectious Diseases Research	000	16	6/14/2004	NON-COMPETING CONTINUATION	$380,000
														Subtotal = $463,640

Issue Date FY: 2003 ( Subtotal = $380,000 )
2003	2003	MCP HAHNEMANN UNIVERSITY	1505 RACE STREET MAIL STOP 485	PHILADELPHIA	PA	19102	PHILADELPHIA	USA	Microbiology and Infectious Diseases Research	000	15		NON-COMPETING CONTINUATION	$380,000
														Subtotal = $380,000

Grand Total All Awards = $10,210,528

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Mitochondrial Functions in Malaria Parasites

Award Number: R01AI028398

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/01/1989

PERIOD OF PERFORMANCE END DATE: 10/31/2028

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