Thursday, March 13, 2025 3/13/2025

Template-based replication of the centriole organelle

Award Number: R01GM088253
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary Reproducible assembly of protein molecules from free amino acids requires external information stored in DNA/RNA (genome). In contrast, assembly of higher-order structures from individual protein molecules is thought to occur de novo, relying on information intrinsic to each protein component. How higher-order complexity emerges efficiently without error using only the scattered information in each building block remains a question hindering core understandings of life. Here we address this question using the biogenesis of the centriole organelle as the example. We found that a proteinaceous structure called the cartwheel is grown inside existing centrioles, which is then split, shed and used as structural templates (or guidance) for reproducing a copy of the centriole with the same size/shape. Uncontrolled cartwheel shedding was further found to underly a human disease called Alström syndrome. By erasing the old guidance, we showed that new/naive centrioles varying widely in size and shape arise, which can propagate reproducibly thereafter in cells otherwise genetically identical. The simplest model explaining our results is that one or more steps of centriole biogenesis are template-based, instructed by information stored and transmitted outside of the genome. This model on which the current proposal is based on will shed light on how cellular complexity emerges reproducibly from components randomly distributed in the cell, redefining the scope of biological information as we currently understood.


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 = $351,370 )
2025	2025	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Biomedical Research and Research Training	001	15	12/9/2024	NON-COMPETING CONTINUATION	$351,370
2025	2023	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Biomedical Research and Research Training	000	13	12/2/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $351,370

Issue Date FY: 2024 ( Subtotal = $612,234 )
2024	2024	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Biomedical Research and Research Training	001	14	9/6/2024	SUPPLEMENT FOR EXPANSION	$221,824
2024	2024	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVENUE	NEW YORK	NY	10065	NEW YORK	USA	Biomedical Research and Research Training	000	14	12/6/2023	COMPETING CONTINUATION	$390,410
														Subtotal = $612,234

Issue Date FY: 2023 ( Subtotal = $386,792 )
2023	2023	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Biomedical Research and Research Training	001	13	2/14/2023	NON-COMPETING CONTINUATION	$38,678
2023	2023	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Biomedical Research and Research Training	000	13	12/15/2022	NON-COMPETING CONTINUATION	$348,114
														Subtotal = $386,792

Issue Date FY: 2022 ( Subtotal = $386,792 )
2022	2022	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Biomedical Research and Research Training	001	12	7/27/2022	NON-COMPETING CONTINUATION	$38,678
2022	2022	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Biomedical Research and Research Training	000	12	12/8/2021	NON-COMPETING CONTINUATION	$348,114
														Subtotal = $386,792

Issue Date FY: 2021 ( Subtotal = $386,792 )
2021	2021	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Biomedical Research and Research Training	000	11	12/17/2020	NON-COMPETING CONTINUATION	$348,115
2021	2021	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Biomedical Research and Research Training	001	11	2/17/2021	NON-COMPETING CONTINUATION	$38,677
														Subtotal = $386,792

Issue Date FY: 2020 ( Subtotal = $386,792 )
2020	2020	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Biomedical Research and Research Training	000	10	12/27/2019	COMPETING CONTINUATION	$386,792
2020	2018	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Biomedical Research and Research Training	001	9	5/7/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $386,792

Issue Date FY: 2018 ( Subtotal = $367,791 )
2018	2018	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Biomedical Research and Research Training	000	9	12/11/2017	NON-COMPETING CONTINUATION	$331,012
2018	2018	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Biomedical Research and Research Training	001	9	6/19/2018	NON-COMPETING CONTINUATION	$36,779
														Subtotal = $367,791

Issue Date FY: 2017 ( Subtotal = $367,791 )
2017	2017	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Biomedical Research and Research Training	000	8	12/22/2016	NON-COMPETING CONTINUATION	$331,012
2017	2017	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Biomedical Research and Research Training	001	8	6/19/2017	NON-COMPETING CONTINUATION	$36,779
														Subtotal = $367,791

Issue Date FY: 2016 ( Subtotal = $367,791 )
2016	2016	SLOAN KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVENUE	NEW YORK	NY	10065	NEW YORK	USA	Biomedical Research and Research Training	000	7	12/8/2015	NON-COMPETING CONTINUATION	$331,012
2016	2016	SLOAN KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVENUE	NEW YORK	NY	10065	NEW YORK	USA	Biomedical Research and Research Training	001	7	3/3/2016	NON-COMPETING CONTINUATION	$36,779
														Subtotal = $367,791

Issue Date FY: 2015 ( Subtotal = $386,980 )
2015	2015	SLOAN KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVENUE	NEW YORK	NY	10065	NEW YORK	USA	Biomedical Research and Research Training	001	6	12/29/2014	COMPETING CONTINUATION	$386,980
2015	2013	SLOAN KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVENUE	NEW YORK	NY	10021	NEW YORK	USA	Biomedical Research and Research Training	000	5	12/24/2014	NON-COMPETING CONTINUATION	$0
														Subtotal = $386,980

Issue Date FY: 2013 ( Subtotal = $343,049 )
2013	2013	SLOAN KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVENUE	NEW YORK	NY	10065	NEW YORK	USA	Biomedical Research and Research Training	000	5	5/29/2013	NON-COMPETING CONTINUATION	$343,049
														Subtotal = $343,049

Issue Date FY: 2012 ( Subtotal = $355,492 )
2012	2012	SLOAN KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVENUE	NEW YORK	NY	10065	NEW YORK	USA	Biomedical Research and Research Training	000	4	5/17/2012	NON-COMPETING CONTINUATION	$355,492
														Subtotal = $355,492

Issue Date FY: 2011 ( Subtotal = $355,492 )
2011	2011	SLOAN KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVENUE	NEW YORK	NY	10065	NEW YORK	USA	Biomedical Research and Research Training	000	3	5/26/2011	NON-COMPETING CONTINUATION	$355,492
														Subtotal = $355,492

Issue Date FY: 2010 ( Subtotal = $359,083 )
2010	2010	SLOAN KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVENUE	NEW YORK	NY	10065	NEW YORK	USA	Biomedical Research and Research Training	000	2	5/17/2010	NON-COMPETING CONTINUATION	$359,083
														Subtotal = $359,083

Issue Date FY: 2009 ( Subtotal = $361,998 )
2009	2009	SLOAN KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVENUE	NEW YORK	NY	10065	NEW YORK	USA	Biomedical Research and Research Training	000	1	7/28/2009	NEW	$361,998
														Subtotal = $361,998

Grand Total All Awards = $5,776,239

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Template-based replication of the centriole organelle

Award Number: R01GM088253

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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