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Chromosome Archae-tecture: Conserved principles of chromosome organization

Award Number: R01GM135178
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: 12/02/2019
PERIOD OF PERFORMANCE END DATE: 11/30/2024

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Chromosome Archae-tecture: Conserved principles of chromosome organization - PROJECT SUMMARY The three-dimensional organization of DNA within cells is of profound importance for the appropriate and timely execution of gene expression programs. Recent advances in experimental approaches have allowed the elucidation of the conformation of chromosomes of bacteria and eukaryotes with unprecedented resolution. Bacterial chromosomes are organized into locally folded units and chromosome arms either side of the origin of replication are juxtaposed processively by the action of SMC proteins. In contrast, metazoa have large-scale domains along the linear order of the chromosome, these fall into two distinct types that exclusively associate to form two distinct classes of higher-order compartment. To date, essentially nothing is known about the conformation of chromosomes from organisms in the third domain of life, the Archaea. Many aspects of the information processing (DNA replication, gene transcription) machineries of archaea and eukaryotes are fundamentally related and distinct from those of bacteria. This is despite the prokaryotic nature of archaea, their morphological similarities to bacteria and the presence of simple circular chromosomes, as in many bacteria. Strikingly, preliminary data reveal that the chromosomes of hyperthermophilic archaea of the genus Sulfolobus, like eukaryotes, and distinct from bacteria, possess a large-scale domain architecture with higher-order organization into two distinct classes of compartment. This provocative observation suggests that the fundamental logic of chromosome organization may predate the bifurcation of archaeal and eukaryotic lineages. The preliminary data will be extended to provide a high-resolution 4-D roadmap of the dynamic structure of the archaeal genome. A novel SMC-related protein is implicated in coordinating the structure of the genome and its role will be investigated both in vivo and in vitro using a combination of genetic and biochemical approaches. Finally, the causality of the interplay between the cellular gene expression program and chromosome architecture will be determined. Taken as a whole, this work will exploit a unique and simple model system to elucidate the mechanisms and evolution of the conserved principles governing the higher-order organization of genomes.


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 = -$6,983 )
2025	2023	TRUSTEES OF INDIANA UNIVERSITY	107 S INDIANA AVE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	000	4	4/16/2025	NON-COMPETING CONTINUATION	-$6,983
														Subtotal = -$6,983

Issue Date FY: 2023 ( Subtotal = $310,597 )
2023	2023	TRUSTEES OF INDIANA UNIVERSITY	107 S INDIANA AVE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	001	4	3/6/2023	NON-COMPETING CONTINUATION	$31,059
2023	2023	TRUSTEES OF INDIANA UNIVERSITY	107 S INDIANA AVE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	000	4	11/17/2022	NON-COMPETING CONTINUATION	$279,538
														Subtotal = $310,597

Issue Date FY: 2022 ( Subtotal = $310,903 )
2022	2022	TRUSTEES OF INDIANA UNIVERSITY	107 S INDIANA AVE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	000	3	11/10/2021	NON-COMPETING CONTINUATION	$279,812
2022	2022	TRUSTEES OF INDIANA UNIVERSITY	107 S INDIANA AVE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	001	3	7/26/2022	NON-COMPETING CONTINUATION	$31,091
														Subtotal = $310,903

Issue Date FY: 2021 ( Subtotal = $311,193 )
2021	2021	TRUSTEES OF INDIANA UNIVERSITY	107 S INDIANA AVENUE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	001	2	3/15/2021	NON-COMPETING CONTINUATION	$31,120
2021	2021	TRUSTEES OF INDIANA UNIVERSITY	107 S INDIANA AVENUE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	000	2	11/24/2020	NON-COMPETING CONTINUATION	$280,073
														Subtotal = $311,193

Issue Date FY: 2020 ( Subtotal = $311,469 )
2020	2020	TRUSTEES OF INDIANA UNIVERSITY	BRYAN HALL 107 S INDIANA AVENUE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	000	1	12/2/2019	NEW	$311,469
														Subtotal = $311,469

Grand Total All Awards = $1,237,179

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Chromosome Archae-tecture: Conserved principles of chromosome organization

Award Number: R01GM135178

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: 12/02/2019

PERIOD OF PERFORMANCE END DATE: 11/30/2024

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