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ENTHALPY ARRAYS FOR THERMODYNAMIC CHARACTERIZATION

Award Number: R01GM077435
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: 06/01/2006
PERIOD OF PERFORMANCE END DATE: 05/31/2010

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ENTHALPY ARRAYS FOR THERMODYNAMIC CHARACTERIZATION - DESCRIPTION (provided by applicant): A generic method to characterize molecular interactions with no assay development would substantially benefit both functional proteomics research and drug discovery; however, none of the available approaches offers the efficient detection and low reagent consumption needed for the large number of measurements. This proposal addresses developing a sensitive enthalpic assay tool to detect bimolecular interactions involving proteins, ligands, RNA, DNA and other molecules of interest without requiring any special assay development. In particular, the assay does not require development of molecule-specific inhibitors, probes, detectors, attachment of labels, immobilization on surfaces, or chemical modifications of the molecules. The assay is based on direct detection of the enthalpy released during interaction of the species of interest. The detector, a nanocalorimeter, will enable measurement of interactions for molecular concentrations in the low micro-molar range using sample volumes of 200 nl. The technical goal of this work is to develop a detector that can detect enthalpies in the nanocalorie range with an effective measurement time of six seconds. This represents nearly three orders of magnitude reduction in the required sample and measurement time compared with conventional microcalorimetry. We propose to develop an array of 96 detectors and use it to study key aspects of HIV infection and life cycle. In addition to detecting interactions the enthalpy array can be used to perform titrations to determine binding constants. The effort integrates several engineering disciplines with applied physics and biochemistry. We have developed the initial proof of concept through a multidisciplinary effort bridging microfabrication with several engineering disciplines (mechanical, electrical chemical and system) as well as applied physics. We are collaborating with several senior biochemists to ensure that the system meets their scientific needs.


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 = $366,326 )
2009	2009	PALO ALTO RESEARCH CENTER	3333 COYOTE HILL ROAD	PALO ALTO	CA	94304	SANTA CLARA	USA	Biomedical Research and Research Training	000	4	6/2/2009	NON-COMPETING CONTINUATION	$366,326
														Subtotal = $366,326

Issue Date FY: 2008 ( Subtotal = $365,236 )
2008	2008	PALO ALTO RESEARCH CENTER	3333 COYOTE HILL ROAD	PALO ALTO	CA	94304	SANTA CLARA	USA	Biomedical Research and Research Training	000	3	5/27/2008	NON-COMPETING CONTINUATION	$365,236
														Subtotal = $365,236

Issue Date FY: 2007 ( Subtotal = $364,190 )
2007	2007	PALO ALTO RESEARCH CENTER	3333 COYOTE HILL ROAD	PALO ALTO	CA	94304	SANTA CLARA	USA	Biomedical Research and Research Training	000	2	5/28/2007	NON-COMPETING CONTINUATION	$364,190
														Subtotal = $364,190

Issue Date FY: 2006 ( Subtotal = $374,033 )
2006	2006	PALO ALTO RESEARCH CENTER	3333 COYOTE HILL ROAD	PALO ALTO	CA	94304	SANTA CLARA	USA	Biomedical Research and Research Training	000	1	5/26/2006	NEW	$374,033
														Subtotal = $374,033

Grand Total All Awards = $1,469,785

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ENTHALPY ARRAYS FOR THERMODYNAMIC CHARACTERIZATION

Award Number: R01GM077435

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: 06/01/2006

PERIOD OF PERFORMANCE END DATE: 05/31/2010

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