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IMAGE BASED PHENOTYPIC PROFILING OF SINGLE-CELL RESPONSES TO PERTURBATIONS

Award Number: R01GM081549
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: 09/01/2007
PERIOD OF PERFORMANCE END DATE: 07/31/2014

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IMAGE BASED PHENOTYPIC PROFILING OF SINGLE-CELL RESPONSES TO PERTURBATIONS - DESCRIPTION (provided by applicant): Increasingly, disease states and responses to therapeutics are seen to be comprised of a heterogeneous mix of cellular states and responses. Insight into the nature of diverse cellular responses to perturbations has immediate applications to pharmacology and disease treatment. Identifying physiologically or clinically important subpopulations, such as cancer drug-resistant or hormone-insensitive cells, is. an important step towards identifying diagnostic biomarkers and developing targeted therapies. Measuring high-dimensional physiological phenotypes of large numbers of individual cells in diverse conditions will enable the characterization of heterogeneous cellular responses to perturbations, and the identification of discrete subpopulations of distinct phenotypic states. Our long term objects are therefore: 1) enabling the detection and comparison of single-cell responses to broad ranges of perturbations; 2) elucidating physiological mechanisms of cellular perturbations; and 3) identifying physiologically important subpopulations. We propose to use immunofluorescence microscopy to monitor complex cellular responses to systematic drug treatments. For the proposed aims, drug treatments are ideal choices for perturbations as they are fast- acting, titratable, and reliable methods for eliciting diverse cellular responses. The specific aims are to: 1. Increase the discriminative capacity of single-cell phenotypic readouts. Single-cell phenotypes, measured independently from small numbers of fluorescent markers, may not distinguish complex cellular states. We will expand readout capacity by increasing the number of markers and quality of readouts per cell, and by correlating readouts of different markers from different cells. 2. Classify perturbation effects using single-cell phenotypic readouts. Classifying the effects of perturbations requires the extraction of informative features from single-cell phenotypic readouts. We will apply new methods for feature selection and drug profiling to the problems of identifying multiphasic and off-target drug effects, and predicting the response to combinations of drug treatments. 3. Represent population heterogeneity as subpopulations of distinct phenotypic states. We will characterize drugs in terms of their effects on these subpopulations of cells.


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 = $0 )
2013	2011	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CTR DALLAS	5323 HARRY HINES BOULEVARD	DALLAS	TX	75235	DALLAS	USA	Biomedical Research and Research Training	000	5	3/26/2013	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2011 ( Subtotal = $327,623 )
2011	2011	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CTR DALLAS	5323 HARRY HINES BOULEVARD	DALLAS	TX	75390	DALLAS	USA	Biomedical Research and Research Training	000	5	7/11/2011	NON-COMPETING CONTINUATION	$327,623
														Subtotal = $327,623

Issue Date FY: 2010 ( Subtotal = $345,483 )
2010	2010	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CTR DALLAS	5323 HARRY HINES BOULEVARD	DALLAS	TX	75390	DALLAS	USA	Biomedical Research and Research Training	000	4	8/2/2010	NON-COMPETING CONTINUATION	$345,483
														Subtotal = $345,483

Issue Date FY: 2009 ( Subtotal = $339,365 )
2009	2009	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CTR DALLAS	5323 HARRY HINES BOULEVARD	DALLAS	TX	75390	DALLAS	USA	Biomedical Research and Research Training	000	3	7/20/2009	NON-COMPETING CONTINUATION	$339,365
														Subtotal = $339,365

Issue Date FY: 2008 ( Subtotal = $368,568 )
2008	2008	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CTR DALLAS	5323 HARRY HINES BOULEVARD	DALLAS	TX	75235	DALLAS	USA	Biomedical Research and Research Training	000	2	7/23/2008	NON-COMPETING CONTINUATION	$368,568
														Subtotal = $368,568

Issue Date FY: 2007 ( Subtotal = $314,000 )
2007	2007	UNIV OF TX ALLERGY & INFECTIOUS DISEASES TRNG GRANT CMT	5323 HARRY HINES BOULEVARD	DALLAS	TX	75235	DALLAS	USA	Biomedical Research and Research Training	000	1	8/27/2007	NEW	$314,000
														Subtotal = $314,000

Grand Total All Awards = $1,695,039

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IMAGE BASED PHENOTYPIC PROFILING OF SINGLE-CELL RESPONSES TO PERTURBATIONS

Award Number: R01GM081549

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: 09/01/2007

PERIOD OF PERFORMANCE END DATE: 07/31/2014

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