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INDUCTION OF CELL CLEAVAGE BY THE MITOTIC SPINDLE

Award Number: R01GM068107
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: 07/01/2005
PERIOD OF PERFORMANCE END DATE: 08/31/2010

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INDUCTION OF CELL CLEAVAGE BY THE MITOTIC SPINDLE - DESCRIPTION (provided by applicant): During mitosis the mitotic spindle communicates essential information to the cell cortex to determine the time and place of cell cleavage. We intend to address the signaling mechanism underlying this fundamental process. Recent analysis in mammalian cells has demonstrated a potential role for passenger proteins such as Survivin, Aurora B, INCENP and TD-60 in this process. Passenger proteins are proteins that migrate from the kinetochores to the spindle equator during late mitosis and have a probable function in signaling the time and position of cleavage furrow formation. Further, three microtubule associated proteins, PRC1, MKLP1 and Cyk-4, are necessary for organization of the midzone spindle. We have done substantial recent work on the roles of Survivin and PRC1 in cell cleavage. We have determined the X-ray structure of Survivin and have demonstrated that it is homodimeric with two extended alpha-helical tails. We have further determined that Survivin is a passenger protein. In a parallel project, we have determined that PRC1 is a microtubule binding protein that is required for bundling of microtubules in the spindle midzone. In the absence of PRC1, depleted by siRNA transfection, the midzone spindle has no organization and cells are incapable of proceeding with cleavage. The primary focus of this application is to conduct a domain analysis of PRC1 and of Survivin in order to understand how the central spindle is constructed in anaphase, to define what role the central spindle plays in organizing the passenger proteins, and to understand the interplay of passenger proteins with the central spindle in the process of signaling cell cleavage.


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: 2010 ( Subtotal = $0 )
2010	2008	BURNHAM INSTITUTE FOR MEDICAL RESEARCH	10901 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Biomedical Research and Research Training	000	5	8/9/2010	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2009 ( Subtotal = $189,454 )
2009	2009	BURNHAM INSTITUTE FOR MEDICAL RESEARCH	10901 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Trans-NIH Recovery Act Research Support	004	5	9/30/2009	SUPPLEMENT FOR EXPANSION	$191,000
2009	2008	BURNHAM INSTITUTE FOR MEDICAL RESEARCH	10901 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Biomedical Research and Research Training	003	5	8/11/2009	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$10,785
2009	2008	SIDNEY KIMMEL CANCER CENTER	10905 Road To The Cure	San Diego	CA	92121	SAN DIEGO	USA	Biomedical Research and Research Training	000	4	7/10/2009	NON-COMPETING CONTINUATION	-$160,205
2009	2008	BURNHAM INSTITUTE FOR MEDICAL RESEARCH	10901 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Biomedical Research and Research Training	002	5	7/10/2009	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$158,545
2009	2008	SIDNEY KIMMEL CANCER CENTER	10905 Road To The Cure	San Diego	CA	92121	SAN DIEGO	USA	Biomedical Research and Research Training	001	4	8/11/2009	NON-COMPETING CONTINUATION	$10,899
														Subtotal = $189,454

Issue Date FY: 2008 ( Subtotal = $402,598 )
2008	2008	SIDNEY KIMMEL CANCER CENTER	10835 ALTMAN ROW	SAN DIEGO	CA	92121	SAN DIEGO	USA	Biomedical Research and Research Training	000	4	6/27/2008	NON-COMPETING CONTINUATION	$402,598
														Subtotal = $402,598

Issue Date FY: 2007 ( Subtotal = $402,598 )
2007	2007	SIDNEY KIMMEL CANCER CENTER	10835 ALTMAN ROW	SAN DIEGO	CA	92121	SAN DIEGO	USA	Biomedical Research and Research Training	000	3	7/16/2007	NON-COMPETING CONTINUATION	$402,598
														Subtotal = $402,598

Issue Date FY: 2006 ( Subtotal = $414,622 )
2006	2006	SIDNEY KIMMEL CANCER CENTER	10835 ALTMAN ROW	SAN DIEGO	CA	92121	SAN DIEGO	USA	Biomedical Research and Research Training	000	2	6/30/2006	NON-COMPETING CONTINUATION	$414,622
														Subtotal = $414,622

Issue Date FY: 2005 ( Subtotal = $425,700 )
2005	2005	SIDNEY KIMMEL CANCER CENTER	10835 ALTMAN ROW	SAN DIEGO	CA	92121	SAN DIEGO	USA	Biomedical Research and Research Training	000	1	5/16/2005	NEW	$425,700
														Subtotal = $425,700

Grand Total All Awards = $1,834,972

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INDUCTION OF CELL CLEAVAGE BY THE MITOTIC SPINDLE

Award Number: R01GM068107

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: 07/01/2005

PERIOD OF PERFORMANCE END DATE: 08/31/2010

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