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High Content Screening of Mycobacterium Tuberculosis

Award Number: R01AI132634
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: 01/01/2020
PERIOD OF PERFORMANCE END DATE: 06/30/2022

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High Content Screening of Mycobacterium Tuberculosis - SUMMARY Tuberculosis (TB) remains a major global health burden with 9.6 million new cases in 2014 and a latently- infected population of billions and deaths from TB now exceed those from HIV. Mtb is a sophisticated pathogen which can persist for decades in the human host and which requires lengthy treatment for cure. One of the features of Mtb is its ability to survive and replicate inside human cells, including macrophages, one of the normal host defense mechanisms against infection. There is an urgent need for new drugs for TB and new drug targets for Mtb. An increased effort in drug discovery has led to the development and application of screening technologies to Mtb; in particular screening against axenically-cultured bacteria. However, laboratory medium and culture conditions do not accurately reproduce the in vivo setting. High-content analysis (HCA) is a powerful screening methodology which uses biologically relevant cell-based assays to identify active compounds in a high throughput manner. For intracellular pathogens, high content screening has the advantage of being able to monitor both bacterial and macrophage cell numbers simultaneously and in the same wells, thus leading to more reliable data and a quicker assessment of compound attractiveness. This proposal addresses NIH announcement PAR-13-364 - Development of Assays for High-Throughput Screening for Use in Probe and Pre-therapeutic Discovery (R01). We propose to develop and run robust and reproducible high content assay(s) for screening against intracellular Mtb. We will run a pilot screen to identify inhibitors which are differentially effective against intracellular bacteria, but which lack cytotoxicity, and so may target novel pathways relevant to infection. We will conduct orthogonal and secondary assays to prioritize compounds for the dual aspects of drug discovery and development, and as chemical probes and initiate target identification studies. This proposal will take advantage of a new facility recently established at our institute with the capability to conduct high throughput, high content screening under BSL3 using state of the art imaging equipment and robotics.


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: 2023 ( Subtotal = -$105,651 )
2023	2019	SEATTLE CHILDREN'S HOSPITAL	4800 SAND POINT WAY NE	SEATTLE	WA	98105	KING	USA	Allergy and Infectious Diseases Research	001	4	8/9/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2023	2019	ACCESS TO ADVANCED HEALTH INSTITUTE	1616 EASTLAKE AVE E	SEATTLE	WA	98102	KING	USA	Allergy and Infectious Diseases Research	000	3	10/11/2022	NON-COMPETING CONTINUATION	-$105,651
														Subtotal = -$105,651

Issue Date FY: 2021 ( Subtotal = $105,651 )
2021	2019	SEATTLE CHILDREN'S HOSPITAL	4800 SAND POINT WAY NE	SEATTLE	WA	98105	KING	USA	Allergy and Infectious Diseases Research	002	4	8/31/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2021	2019	SEATTLE CHILDREN'S HOSPITAL	4800 SAND POINT WAY NE	SEATTLE	WA	98105	KING	USA	Allergy and Infectious Diseases Research	001	4	4/15/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$52,825
2021	2018	INFECTIOUS DISEASE RESEARCH INSTITUTE	1616 EASTLAKE AVE E STE 400	SEATTLE	WA	98102	KING	USA	Allergy and Infectious Diseases Research	000	2	4/15/2021	NON-COMPETING CONTINUATION	$52,825
														Subtotal = $105,651

Issue Date FY: 2020 ( Subtotal = $13,443 )
2020	2019	SEATTLE CHILDREN'S HOSPITAL	4800 SAND PT WAY NE	SEATTLE	WA	98105	KING	USA	Allergy and Infectious Diseases Research	001	4	5/18/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$649,245
2020	2019	INFECTIOUS DISEASE RESEARCH INSTITUTE	1616 EASTLAKE AVE E STE 400	SEATTLE	WA	98102	KING	USA	Allergy and Infectious Diseases Research	000	3	5/15/2020	NON-COMPETING CONTINUATION	-$635,802
														Subtotal = $13,443

Issue Date FY: 2019 ( Subtotal = $635,802 )
2019	2019	INFECTIOUS DISEASE RESEARCH INSTITUTE	1616 EASTLAKE AVE E STE 400	SEATTLE	WA	98102	KING	USA	Allergy and Infectious Diseases Research	000	3	6/18/2019	NON-COMPETING CONTINUATION	$635,802
														Subtotal = $635,802

Issue Date FY: 2018 ( Subtotal = $631,092 )
2018	2018	INFECTIOUS DISEASE RESEARCH INSTITUTE	1616 EASTLAKE AVE E STE 400	SEATTLE	WA	98102	KING	USA	Allergy and Infectious Diseases Research	000	2	6/19/2018	NON-COMPETING CONTINUATION	$631,092
														Subtotal = $631,092

Issue Date FY: 2017 ( Subtotal = $646,203 )
2017	2017	INFECTIOUS DISEASE RESEARCH INSTITUTE	1616 EASTLAKE AVE E STE 400	SEATTLE	WA	98102	KING	USA	Allergy and Infectious Diseases Research	000	1	7/12/2017	NEW	$646,203
														Subtotal = $646,203

Grand Total All Awards = $1,926,540

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High Content Screening of Mycobacterium Tuberculosis

Award Number: R01AI132634

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: 01/01/2020

PERIOD OF PERFORMANCE END DATE: 06/30/2022

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