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ADHERENCE OF MALARIA-INFECTED RED CELLS

Award Number: R01AI044008
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: 01/01/1999
PERIOD OF PERFORMANCE END DATE: 02/28/2010

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ADHERENCE OF MALARIA-INFECTED RED CELLS - DESCRIPTION (provided by the applicant): The etiological agent responsible for the severe form of malaria in humans is the intraerythrocytic protozoan parasite Plasmodium falciparum. Clinical manifestations of P. falciparum malaria include cerebral malaria, a major cause of death from this disease, where infected erythrocytes sequester in the deep vascular beds of the brain. During growth of the asexual stage of the parasite in human erythrocytes, extensive changes occur in the structural and functional properties of the infected erythrocyte, including the development of knob structures and the ability to adhere to endothelium. Crucial to these changes are proteins of parasite origin that are either deposited on the inner aspect of the erythrocyte membrane or inserted into it. Several parasite proteins are present at the cytoplasmic side of the knob structure including the krab-associated histidine rich protein and PfEMP3. The adhesive properties of P. falciparum infected erythrocytes are due to the antigenically variant protein PfEMPI that is concentrated in the knob on the outside of the membrane. Transport of proteins to the erythrocyte cytoskeleton and surface is a multi-step process involving trafficking across the parasite membrane, parasitophorous vacuole membrane and into the REIC cytoplasm where they can associate with membranous structures know as Maurer's clefts and from there reach their final destination. An understanding of this trafficking process is an important biological question but significantly will provide the basis for novel experimental approaches to identify and elucidate the role of exported proteins in the adhesive and mechanical properties of P. falciparum-infected erythrocytes. We hypothesize that interaction of these proteins with Maurer's clefts and subsequent trafficking steps are essential for correct localization and function involving defined targeting motifs and protein-protein interactions, To test these hypotheses, we will make P.falciparum transfectants lacking expression of defined proteins, express mutant forms or chimeric proteins that can be analyzed. We will use this information to define a core subset of proteins exported to the erythrocyte by the parasite responsible for remodeling of the erythrocyte. Functional analysis of these proteins will increase our understanding of the role of proteins in the regulation of cell structure and the mechanical and adhesive properties. These studies will contribute to and increased understanding of the pathophysiology of falciparum malaria.


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: 2009 ( Subtotal = $200,916 )
2009	2009	WALTER & ELIZA HALL INSTITUTION OF MEDICINE	ROYAL MELBOURNE HOSPITAL	MELBOURNE				AUS	Allergy and Infectious Diseases Research	000	11	2/19/2009	NON-COMPETING CONTINUATION	$180,824
2009	2009	WALTER & ELIZA HALL INSTITUTION OF MEDICINE	ROYAL MELBOURNE HOSPITAL	MELBOURNE				AUS	Allergy and Infectious Diseases Research	001	11	6/26/2009	NON-COMPETING CONTINUATION	$20,092
														Subtotal = $200,916

Issue Date FY: 2008 ( Subtotal = $200,916 )
2008	2008	WALTER & ELIZA HALL INSTITUTION OF MEDICINE	ROYAL MELBOURNE HOSPITAL	MELBOURNE		00000		AUS	Allergy and Infectious Diseases Research	000	10	2/7/2008	NON-COMPETING CONTINUATION	$200,916
														Subtotal = $200,916

Issue Date FY: 2007 ( Subtotal = $204,807 )
2007	2007	WALTER & ELIZA HALL INSTITUTION OF MEDICINE	ROYAL MELBOURNE HOSPITAL	MELBOURNE		00000		AUS	Allergy and Infectious Diseases Research	000	9	3/7/2007	NON-COMPETING CONTINUATION	$204,807
														Subtotal = $204,807

Issue Date FY: 2006 ( Subtotal = $210,924 )
2006	2006	WALTER & ELIZA HALL INSTITUTION OF MEDICINE	ROYAL MELBOURNE HOSPITAL	MELBOURNE		00000		AUS	Allergy and Infectious Diseases Research	000	8	2/2/2006	NON-COMPETING CONTINUATION	$210,924
														Subtotal = $210,924

Issue Date FY: 2005 ( Subtotal = $108,000 )
2005	2005	WALTER & ELIZA HALL INSTITUTION OF MEDICINE	ROYAL MELBOURNE HOSPITAL	MELBOURNE		00000		AUS	Microbiology and Infectious Diseases Research	000	7	5/24/2005	COMPETING CONTINUATION	$108,000
														Subtotal = $108,000

Issue Date FY: 2004 ( Subtotal = $162,000 )
2004	2004	WALTER & ELIZA HALL INSTITUTE	PO ROYAL MELBOURNE HOSPITAL	VICTORIA		0		AUS	Microbiology and Infectious Diseases Research	000	6	8/9/2004	NON-COMPETING CONTINUATION	$162,000
														Subtotal = $162,000

Issue Date FY: 2003 ( Subtotal = $162,000 )
2003	2003	WALTER & ELIZA HALL INSTITUTE	PO ROYAL MELBOURNE HOSPITAL	VICTORIA		0		AUS	Microbiology and Infectious Diseases Research	000	5	7/17/2003	NON-COMPETING CONTINUATION	$162,000
														Subtotal = $162,000

Issue Date FY: 2002 ( Subtotal = $162,000 )
2002	2002	WALTER & ELIZA HALL INSTITUTE	PO ROYAL MELBOURNE HOSPITAL	VICTORIA		0		AUS	Microbiology and Infectious Diseases Research	000	4	9/2/2002	COMPETING CONTINUATION	$162,000
														Subtotal = $162,000

Issue Date FY: 2001 ( Subtotal = $123,462 )
2001	2001	WALTER & ELIZA HALL INSTITUTE	PO ROYAL MELBOURNE HOSPITAL	VICTORIA		0		AUS	Microbiology and Infectious Diseases Research	000	3	1/5/2001	NON-COMPETING CONTINUATION	$123,462
														Subtotal = $123,462

Issue Date FY: 2000 ( Subtotal = $119,866 )
2000	2000	WALTER & ELIZA HALL INSTITUTE	PO ROYAL MELBOURNE HOSPITAL	VICTORIA		0		AUS	Microbiology and Infectious Diseases Research	000	2	1/20/2000	NON-COMPETING CONTINUATION	$119,866
														Subtotal = $119,866

Issue Date FY: 1999 ( Subtotal = $116,375 )
1999	1999	WALTER & ELIZA HALL INSTITUTE	PO ROYAL MELBOURNE HOSPITAL	VICTORIA		0		AUS	Microbiology and Infectious Diseases Research	000	1	12/31/1998	NEW	$116,375
														Subtotal = $116,375

Grand Total All Awards = $1,771,266

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ADHERENCE OF MALARIA-INFECTED RED CELLS

Award Number: R01AI044008

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: 01/01/1999

PERIOD OF PERFORMANCE END DATE: 02/28/2010

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