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Characterization of Biofilms by Correlated Mass Spectrometric and Raman Imaging

Award Number: R01AI113219
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: 06/01/2014
PERIOD OF PERFORMANCE END DATE: 08/31/2025

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Characterization of Biofilms by Correlated Mass Spectrometric and Raman Imaging - PROJECT SUMMARY Most bacteria in natural and clinical settings grow as surface-attached biofilms, which are bacterial communities that have self-assembled into an encased matrix of extracellular polymeric substances (EPS). To form these bacterial biofilm communities and infect host cells, an intercellular signaling process described as quorum sensing (QS) is very important. For the opportunistic pathogens Pseudomonas aeruginosa and Staphylococcus aureus, QS regulates the expression of many genes important to biofilm initiation, EPS production, and virulence. While much has been learned about select factors that regulate biofilm formation in vitro and in animal models, the specific mechanisms by which multispecies groups of cells form biofilms are not understood. Furthermore, the therapeutic capabilities needed to treat the increasingly virulent infections of the coming decades will require deeper insight into multi-species interactions and their regulation of multiple gene expression profiles as represented over extended spatial and temporal scales during host cell infection. The correlated mass spectrometric and Raman chemical imaging approaches that have been developed by our combined research group circumvent the limitations imposed by previous technology which allowed examination of either a small number of cells or entire cell populations that had been removed from the conditions of interest. In contrast our correlated chemical imaging methods allow the determination and spatial mapping of individual bacterial species and their microbial products within a mixed bacterial community growing in situ on surfaces. One of our long-term goals is the design of detection and diagnostic strategies informed by an understanding of bacterial interactions and signature biomolecule production. We will continue our work toward this goal by conducting mono-culture and co-culture experiments using Pseudomonas aeruginosa and Staphylococcus aureus as model pathogens. Correlated chemical imaging will be used to define the onset and range of intercellular quorum sensing signaling in space and time. The biosecretome and interactions of specific species in co-culture biofilms will be characterized for both intra- and inter-species interactions. Also, an ex vivo lung assay will be created to study the spatial biofilm secretome. This research will exploit the ability to spatially map specific chemical products produced by these and other pathogenic bacteria thereby yielding deep and therapeutically informative insights into host colonization, infection, and virulence.


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: 2026 ( Subtotal = -$195 )
2026	2023	UNIVERSITY OF NOTRE DAME DU LAC	940 GRACE HALL	NOTRE DAME	IN	46556	ST JOSEPH	USA	Allergy and Infectious Diseases Research	000	10	12/15/2025	NON-COMPETING CONTINUATION	-$195
														Subtotal = -$195

Issue Date FY: 2023 ( Subtotal = $503,533 )
2023	2023	UNIVERSITY OF NOTRE DAME DU LAC	940 GRACE HALL	NOTRE DAME	IN	46556	ST JOSEPH	USA	Allergy and Infectious Diseases Research	000	10	8/11/2023	NON-COMPETING CONTINUATION	$503,533
														Subtotal = $503,533

Issue Date FY: 2022 ( Subtotal = $503,533 )
2022	2022	UNIVERSITY OF NOTRE DAME DU LAC	940 GRACE HALL	NOTRE DAME	IN	46556	ST JOSEPH	USA	Allergy and Infectious Diseases Research	000	9	8/18/2022	NON-COMPETING CONTINUATION	$503,533
														Subtotal = $503,533

Issue Date FY: 2021 ( Subtotal = $503,533 )
2021	2021	UNIVERSITY OF NOTRE DAME DU LAC	940 GRACE HALL	NOTRE DAME	IN	46556	ST JOSEPH	USA	Allergy and Infectious Diseases Research	000	8	8/10/2021	NON-COMPETING CONTINUATION	$503,533
														Subtotal = $503,533

Issue Date FY: 2020 ( Subtotal = $500,779 )
2020	2020	UNIVERSITY OF NOTRE DAME DU LAC	940 GRACE HALL	NOTRE DAME	IN	46556	ST JOSEPH	USA	Allergy and Infectious Diseases Research	001	7	8/7/2020	NON-COMPETING CONTINUATION	$500,779
2020	2018	UNIVERSITY OF NOTRE DAME DU LAC	940 GRACE HALL	NOTRE DAME	IN	46556	ST JOSEPH	USA	Allergy and Infectious Diseases Research	000	5	2/4/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $500,779

Issue Date FY: 2019 ( Subtotal = $509,546 )
2019	2019	UNIVERSITY OF NOTRE DAME DU LAC	940 GRACE HALL	NOTRE DAME	IN	46556	ST JOSEPH	USA	Allergy and Infectious Diseases Research	000	6	9/19/2019	COMPETING CONTINUATION	$509,546
														Subtotal = $509,546

Issue Date FY: 2018 ( Subtotal = $422,282 )
2018	2018	UNIVERSITY OF NOTRE DAME DU LAC	940 GRACE HALL	NOTRE DAME	IN	46556	ST JOSEPH	USA	Allergy and Infectious Diseases Research	000	5	6/1/2018	NON-COMPETING CONTINUATION	$422,282
														Subtotal = $422,282

Issue Date FY: 2017 ( Subtotal = $430,230 )
2017	2017	UNIVERSITY OF NOTRE DAME DU LAC	940 GRACE HALL	NOTRE DAME	IN	46556	ST JOSEPH	USA	Allergy and Infectious Diseases Research	000	4	4/20/2017	NON-COMPETING CONTINUATION	$430,230
														Subtotal = $430,230

Issue Date FY: 2016 ( Subtotal = $437,958 )
2016	2016	UNIVERSITY OF NOTRE DAME	801 GRACE HALL	NOTRE DAME	IN	46556	ST JOSEPH	USA	Allergy and Infectious Diseases Research	000	3	5/27/2016	NON-COMPETING CONTINUATION	$437,958
														Subtotal = $437,958

Issue Date FY: 2015 ( Subtotal = $445,455 )
2015	2015	UNIVERSITY OF NOTRE DAME	801 GRACE HALL	NOTRE DAME	IN	46556	ST JOSEPH	USA	Allergy and Infectious Diseases Research	000	2	5/6/2015	NON-COMPETING CONTINUATION	$445,455
														Subtotal = $445,455

Issue Date FY: 2014 ( Subtotal = $465,734 )
2014	2014	UNIVERSITY OF NOTRE DAME	801 GRACE HALL	NOTRE DAME	IN	46556	ST JOSEPH	USA	Allergy and Infectious Diseases Research	000	1	5/22/2014	NEW	$465,734
														Subtotal = $465,734

Grand Total All Awards = $4,722,388

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Characterization of Biofilms by Correlated Mass Spectrometric and Raman Imaging

Award Number: R01AI113219

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: 06/01/2014

PERIOD OF PERFORMANCE END DATE: 08/31/2025

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