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ROLE OF RNA SILENCING AS AN ANTIVIRAL DEFENSE MECHANISM IN FUNGI

Award Number: R01AI076219
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: 12/09/2008
PERIOD OF PERFORMANCE END DATE: 11/30/2014

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ROLE OF RNA SILENCING AS AN ANTIVIRAL DEFENSE MECHANISM IN FUNGI - Project Summary RNA silencing pathways operate in all eukaryotic kingdoms and have been implicated in a range of processes including translational silencing, post-transcriptional RNA degradation, transcriptional gene silencing due to heterochromatin formation or DNA methylation and meiotic elimination or silencing of unpaired DNA. RNA silencing has also been shown to serve as an antivrial defense mechanism in plants, invertebrates, and fungi and to modulate animal virus infections. The antiviral function of RNA silencing not only protects an organism against virus infection, but the generation of virus-derived small RNA products (vsRNAs) and the expression of counter-acting virus-encoded suppressors of RNA silencing can also significantly influence host gene expression and phenotype by impinging on the larger RNA silencing pathway. Although considerable progress has been made in elucidating the core features of the RNA silencing antiviral defense response, and essential components, both host- and virus-encoded, involved in this interaction have been identified, many important details remain unresolved. The Specific Aims of this proposal are designed to address outstanding questions related to a) the origins and properties of vsRNAs, b) the potential for these small RNAs to alter host gene expression in persistent virus infections, and c) molecular mechanisms involved in virus-mediated induction and suppression of RNA silencing pathways. The Research Design takes advantage of a powerful experimental system consisting of a tractable eukaryotic organism, the chestnut blight fungus Cryphonectria parasitica, with a simplified antiviral pathway (involving a single Dicer and single Argonaute) that is the natural host of a constellation of well-characterized viruses with different replication strategies and properties representing five different virus taxonomic families. The results derived from completion of the proposed research will have broad relevance to ongoing efforts to understand the complex interactions between viruses and cellular RNA silencing pathways and the impact that these interactions have on the host. The influence of fungal RNA silencing antiviral pathways clearly needs to be considered in any current and future use of mycoviruses for experimental or therapeutic manipulation of the fungal host, e.g., biological control of fungal virulence or mycotoxin production. Finally, preliminary data already indicates that the evolutionary position of fungi relative to animals and plants will provide insights into novel mechanisms for the induction and suppression of RNA silencing pathways yet to be revealed in the other organisms.


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: 2013 ( Subtotal = $345,486 )
2013	2013	UNIVERSITY OF MARYLAND	4101 CHESAPEAKE BLDG	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	000	6	11/15/2012	NON-COMPETING CONTINUATION	$330,785
2013	2013	UNIVERSITY OF MARYLAND	4101 CHESAPEAKE BLDG	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	001	6	5/24/2013	NON-COMPETING CONTINUATION	$14,701
														Subtotal = $345,486

Issue Date FY: 2012 ( Subtotal = $367,538 )
2012	2012	UNIVERSITY OF MARYLAND	4101 CHESAPEAKE BLDG	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	001	5	5/30/2012	NON-COMPETING CONTINUATION	$36,753
2012	2012	UNIVERSITY OF MARYLAND	4101 CHESAPEAKE BLDG	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	000	5	11/15/2011	NON-COMPETING CONTINUATION	$330,785
														Subtotal = $367,538

Issue Date FY: 2011 ( Subtotal = $367,538 )
2011	2011	UNIVERSITY OF MARYLAND	4101 CHESAPEAKE BLDG	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	000	4	11/17/2010	NON-COMPETING CONTINUATION	$334,125
2011	2011	UNIVERSITY OF MARYLAND	4101 CHESAPEAKE BLDG	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	001	4	6/3/2011	NON-COMPETING CONTINUATION	$33,413
														Subtotal = $367,538

Issue Date FY: 2010 ( Subtotal = $371,250 )
2010	2010	MARYLAND BIOTECHNOLOGY INSTITUTE	701 E PRATT STREET, SUITE 200	BALTIMORE	MD	21202	BALTIMORE CITY	USA	Allergy and Infectious Diseases Research	000	2	12/1/2009	NON-COMPETING CONTINUATION	$337,500
2010	2010	UNIVERSITY OF MARYLAND	4101 CHESAPEAKE BLDG	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	002	3	5/21/2010	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$265,050
2010	2010	MARYLAND BIOTECHNOLOGY INSTITUTE	701 E PRATT STREET, SUITE 200	BALTIMORE	MD	21202	BALTIMORE CITY	USA	Allergy and Infectious Diseases Research	001	2	4/22/2010	NON-COMPETING CONTINUATION	$33,750
2010	2010	MARYLAND BIOTECHNOLOGY INSTITUTE	701 E PRATT STREET, SUITE 200	BALTIMORE	MD	21202	BALTIMORE CITY	USA	Allergy and Infectious Diseases Research	003	2	5/21/2010	NON-COMPETING CONTINUATION	-$265,050
														Subtotal = $371,250

Issue Date FY: 2009 ( Subtotal = $375,000 )
2009	2009	MARYLAND BIOTECHNOLOGY INSTITUTE	701 E PRATT STREET, SUITE 200	BALTIMORE	MD	21202	BALTIMORE CITY	USA	Allergy and Infectious Diseases Research	000	1	12/5/2008	NEW	$375,000
														Subtotal = $375,000

Grand Total All Awards = $1,826,812

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ROLE OF RNA SILENCING AS AN ANTIVIRAL DEFENSE MECHANISM IN FUNGI

Award Number: R01AI076219

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: 12/09/2008

PERIOD OF PERFORMANCE END DATE: 11/30/2014

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