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CONGENITAL MYELOID FAILURE SYNDROMES

Award Number: R01HL079545
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/30/2004
PERIOD OF PERFORMANCE END DATE: 07/31/2009

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CONGENITAL MYELOID FAILURE SYNDROMES - DESCRIPTION (provided by applicant): Congenital myeloid failure syndromes are a heterogeneous group of rare hereditary disorders associated with considerable morbidity. Despite recent insights into the genetic basis for a subset of these disorders, the molecular pathogenesis of others remains unknown. Our goal is to use a forward genetic approach in a model vertebrate, the zebrafish, to develop animal models of hereditary myeloid failure. Comprehensive characterization of these models, coupled with their genetic elucidation, will lead to new knowledge about the molecular pathogenesis of these disorders, aiding their diagnosis, treatment and possibly prevention. A group of zebrafish mutants with myeloid failure has been generated by ethylnitrosourea mutagenesis and genetic screening. Ten stable mutant pedigrees have been recovered to date (a recovery rate of 83%), and >15 more are at various stages of recovery. This project aims to (1) characterize the mutants descriptively using microscopy, histology, whole mount in situ hybridization gene expression analysis, and transplantation assays; (2) position all the mutants on the zebrafish genome map in their respective linkage groups; (3) positionally clone 6 of the mutants, prioritized for the particular biological interest of their phenotypes. Having identified the genetic basis of these particularly interesting myeloid-failure mutants, we will better understand the function of these genes in the molecular and cellular mechanisms of myeloid cell development. Because of the unbiased nature of generating the mutants, some of them are expected to reveal completely new insights into the causes of congenital myeloid failure. Other mutants, found to have novel mutations in genes already associated with myelopoiesis, will likely reveal new insights into the molecular pathogenesis of myeloid cell disease and normal myeloid cell proliferation, differentiation, survival and function. A better understanding of normal myeloid cell development will also help understand the basis for the dysregulation of these processes in myeloproliferative and leukemic diseases.


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: 2008 ( Subtotal = $256,009 )
2008	2008	WALTER & ELIZA HALL INSTITUTION OF MEDICINE	ROYAL MELBOURNE HOSPITAL	MELBOURNE		00000		AUS	Blood Diseases and Resources Research	000	6	7/15/2008	NON-COMPETING CONTINUATION	$256,009
														Subtotal = $256,009

Issue Date FY: 2007 ( Subtotal = $256,009 )
2007	2007	WALTER & ELIZA HALL INSTITUTION OF MEDICINE	ROYAL MELBOURNE HOSPITAL	MELBOURNE		00000		AUS	Blood Diseases and Resources Research	000	5	7/24/2007	NON-COMPETING CONTINUATION	$256,009
														Subtotal = $256,009

Issue Date FY: 2006 ( Subtotal = $263,655 )
2006	2006	WALTER & ELIZA HALL INSTITUTION OF MEDICINE	ROYAL MELBOURNE HOSPITAL	MELBOURNE		00000		AUS	Blood Diseases and Resources Research	000	4	8/21/2006	NON-COMPETING CONTINUATION	$263,655
														Subtotal = $263,655

Issue Date FY: 2005 ( Subtotal = $270,000 )
2005	2005	ROYAL MELBOURNE HOSPITAL	PARKVILLE 3050	VICTORIA		00000		AUS	Blood Diseases and Resources Research	000	2	8/1/2005	NON-COMPETING CONTINUATION	$270,000
														Subtotal = $270,000

Issue Date FY: 2004 ( Subtotal = $270,000 )
2004	2004	ROYAL MELBOURNE HOSPITAL	PARKVILLE 3050	VICTORIA		00000		AUS	Blood Diseases and Resources Research	000	1	9/23/2004	NEW	$270,000
														Subtotal = $270,000

Grand Total All Awards = $1,315,673

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CONGENITAL MYELOID FAILURE SYNDROMES

Award Number: R01HL079545

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/30/2004

PERIOD OF PERFORMANCE END DATE: 07/31/2009

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