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Development-Associated Linear Chromosome Segregation in Streptomyces

Award Number: R15GM148966
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: 09/20/2022
PERIOD OF PERFORMANCE END DATE: 08/31/2026

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Development-Associated Linear Chromosome Segregation in Streptomyces - Project Summary Streptomyces are ubiquitous filamentous sporulating soil bacteria, important in the environment because they degrade and recycle the nutrients locked in many recalcitrant natural polymers in the soil (e.g., cellulose and chitin) and produce the majority of a wide range of biologically active compounds that are used extensively in human and veterinary medicine (e.g., antibiotic, antiviral, anticancer, antitumor, antifungal, immunosuppressant and anthelmintic pharmaceuticals). Streptomyces are also well known as one of the major producers of the compounds that give soil its characteristic earthy odor. These organisms have large linear genomes. Little is known about the architecture of the linear chromosome within the Streptomyces spore and the mechanisms which govern its development-associated genome segregation and nucleoid condensation during spore formation are poorly understood. The ultimate goal from the proposed basic research is to have a better understanding of the novel cellular processes of these distinctive organisms of tremendous medical importance. The unusual mycelial life cycle and linear structure of the Streptomyces genome are likely to require some unique solutions to the fundamental problems of genome segregation and condensation. The first specific aim of the proposal is to characterize a novel small coiled-coil protein that is exclusive to this group of organisms. A genetic approach was used to provide evidence that this protein is involved in development-associated genome segregation. A proximity-labeling approach, with a promiscuous biotin ligase fusion, is being used to identify proteins that interact with this novel protein in vivo. Alanine-scanning and random PCR-directed mutageneses are being used to identify residues important for protein-protein interaction with one known binding partner. The second specific aim is to characterize type VII secretion system ATPase proteins. In addition to their functions in protein secretion, the ATPase proteins are moonlighting in development-associated segregation and nucleoid condensation. A genetic approach will be used to dissect the first type VII secretion ATPase to identify the region(s) needed for genome segregation. A genetic approach will also be used to determine the parts of both type VII secretion ATPases to identify the regions necessary for correct nucleoid condensation in the spore. Mutants lacking genes encoding both type VII secretion ATPases have genomes organized against the spore periphery (doughnut-shaped) instead of being condensed as an ellipsoid nucleoid in the center of the spore.


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: 2025 ( Subtotal = $0 )
2025	2024	DUQUESNE UNIVERSITY OF THE HOLY SPIRIT	600 FORBES AVENUE	PITTSBURGH	PA	15282	ALLEGHENY	USA	Biomedical Research and Research Training	001	1	9/10/2025	SUPPLEMENT FOR EXPANSION	$0
2025	2022	DUQUESNE UNIVERSITY OF THE HOLY SPIRIT	600 FORBES AVENUE	PITTSBURGH	PA	15282	ALLEGHENY	USA	Biomedical Research and Research Training	000	1	9/10/2025	NEW	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $29,510 )
2024	2024	DUQUESNE UNIVERSITY OF THE HOLY SPIRIT	600 FORBES AVENUE	PITTSBURGH	PA	15282	ALLEGHENY	USA	Biomedical Research and Research Training	000	1	5/15/2024	SUPPLEMENT FOR EXPANSION	$29,510
														Subtotal = $29,510

Issue Date FY: 2022 ( Subtotal = $401,069 )
2022	2022	DUQUESNE UNIVERSITY OF THE HOLY SPIRIT	600 FORBES AVENUE	PITTSBURGH	PA	15282	ALLEGHENY	USA	Biomedical Research and Research Training	000	1	9/20/2022	NEW	$401,069
														Subtotal = $401,069

Grand Total All Awards = $430,579

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Development-Associated Linear Chromosome Segregation in Streptomyces

Award Number: R15GM148966

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: 09/20/2022

PERIOD OF PERFORMANCE END DATE: 08/31/2026

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