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Structural, spatial, and temporal features guiding amelogenins transformation of calcium phosphate into enamel

Award Number: R01DE015347
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary The goal of the proposed work is to develop a molecular level, structural understanding of the role of amelogenin in directing the hierarchical growth of enamel. Enamel is one of the hardest biominerals known, and is hierarchically structured to prevent crack propagation, allowing it to last many people a lifetime. However, naturally occurring diseases or damage do occur to enamel and our current therapies fall far short of nature made enamel. Over the past decade we have come to understand that amelogenin assembles into quaternary structures as oligomers containing 12 proteins, units which further assemble into nanospheres. These assemblies, the molecular level interactions governing them, their interactions with calcium phosphate, and their role in mineral phase transformations, are not well understood for enamel formation. We do know that the protein amelogenin, the predominant protein in the forming enamel milieu, is critical in formation based on amelogenin null mouse models showing severely damaged enamel phenotypes. Protein structure often dictates function, yet we have only begun to reveal the structure of amelogenin. Further, the mineral in the enamel milieu begins as ions, and transitions through an amorphous stage prior to becoming elongated, crystallized HAP needles. Both in vivo and in vitro studies have demonstrated that amelogenin controls this phase transformation process, but the structural, spatial, and temporal aspects of this process are not understood. In our proposed work, we bring a set of advanced characterization techniques to an in vitro system simulating developing enamel to evaluate the structure of amelogenin when interacting with calcium phosphates, to understand the spatial distribution of amelogenin around developing calcium phosphate mineral ribbons, and to develop a molecular level view of the transformation process from calcium phosphate clusters, through the amorphous phase, on to crystalline HAP. This suite of techniques has never been brought to bear on understanding the challenge of enamel growth and will result in an understanding of the development of enamel that is currently lacking. The results of this work are relevant to biomineralization systems in general and may ultimately inform more robust therapeutics for enamel replacements.


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 = $495,401 )
2023	2023	BATTELLE MEMORIAL INSTITUTE	902 BATTELLE BLVD	RICHLAND	WA	99354	BENTON	USA	Oral Diseases and Disorders Research	001	16	7/25/2023	NON-COMPETING CONTINUATION	$487,625
2023	2019	BATTELLE MEMORIAL INSTITUTE	902 BATTELLE BLVD	RICHLAND	WA	99354	BENTON	USA	Oral Diseases and Disorders Research	000	13	11/23/2022	NON-COMPETING CONTINUATION	$7,776
														Subtotal = $495,401

Issue Date FY: 2022 ( Subtotal = $482,748 )
2022	2022	BATTELLE MEMORIAL INSTITUTE	900 BATTELLE BLVD	RICHLAND	WA	99352	BENTON	USA	Oral Diseases and Disorders Research	002	15	8/10/2022	NON-COMPETING CONTINUATION	$482,748
2022	2021	BATTELLE MEMORIAL INSTITUTE	902 BATTELLE BLVD	RICHLAND	WA	99354	BENTON	USA	Oral Diseases and Disorders Research	001	14	4/15/2022	COMPETING CONTINUATION	$10,620
2022	2019	BATTELLE MEMORIAL INSTITUTE	902 BATTELLE BLVD	RICHLAND	WA	99354	BENTON	USA	Oral Diseases and Disorders Research	000	13	4/15/2022	NON-COMPETING CONTINUATION	-$10,620
														Subtotal = $482,748

Issue Date FY: 2021 ( Subtotal = $487,625 )
2021	2021	BATTELLE MEMORIAL INSTITUTE	900 BATTELLE BLVD	RICHLAND	WA	99352	BENTON	USA	Oral Diseases and Disorders Research	000	14	8/18/2021	COMPETING CONTINUATION	$487,625
														Subtotal = $487,625

Issue Date FY: 2019 ( Subtotal = $519,215 )
2019	2019	BATTELLE MEMORIAL INSTITUTE	900 BATTELLE BLVD	RICHLAND	WA	99352	BENTON	USA	Oral Diseases and Disorders Research	000	13	7/16/2019	NON-COMPETING CONTINUATION	$519,215
														Subtotal = $519,215

Issue Date FY: 2018 ( Subtotal = $519,215 )
2018	2018	BATTELLE MEMORIAL INSTITUTE	900 BATTELLE BLVD	RICHLAND	WA	99352	BENTON	USA	Oral Diseases and Disorders Research	000	12	7/19/2018	NON-COMPETING CONTINUATION	$519,215
														Subtotal = $519,215

Issue Date FY: 2017 ( Subtotal = $519,215 )
2017	2017	BATTELLE MEMORIAL INSTITUTE	900 BATTELLE BLVD	RICHLAND	WA	99352	BENTON	USA	Oral Diseases and Disorders Research	000	11	8/1/2017	NON-COMPETING CONTINUATION	$519,215
														Subtotal = $519,215

Issue Date FY: 2016 ( Subtotal = $519,215 )
2016	2016	PACIFIC NORTHWEST LAB, DIV OF BATTELLE MEMORIAL INST	POST OFFICE BOX 999	RICHLAND	WA	99352	BENTON	USA	Oral Diseases and Disorders Research	000	10	7/25/2016	NON-COMPETING CONTINUATION	$519,215
														Subtotal = $519,215

Issue Date FY: 2015 ( Subtotal = $519,215 )
2015	2015	PACIFIC NORTHWEST LAB, DIV OF BATTELLE MEMORIAL INST	POST OFFICE BOX 999	RICHLAND	WA	99352	BENTON	USA	Oral Diseases and Disorders Research	000	9	7/20/2015	COMPETING CONTINUATION	$519,215
														Subtotal = $519,215

Issue Date FY: 2013 ( Subtotal = $495,667 )
2013	2013	PACIFIC NORTHWEST LAB, DIV OF BATTELLE MEMORIAL INST	POST OFFICE BOX 999	RICHLAND	WA	99352	BENTON	USA	Oral Diseases and Disorders Research	000	8	5/21/2013	NON-COMPETING CONTINUATION	$357,139
2013	2013	PACIFIC NORTHWEST LAB, DIV OF BATTELLE MEMORIAL INST	POST OFFICE BOX 999	RICHLAND	WA	99352	BENTON	USA	Oral Diseases and Disorders Research	001	8	9/3/2013	SUPPLEMENT FOR EXPANSION	$138,528
														Subtotal = $495,667

Issue Date FY: 2012 ( Subtotal = $377,181 )
2012	2012	PACIFIC NORTHWEST LAB, DIV OF BATTELLE MEMORIAL INST	POST OFFICE BOX 999	RICHLAND	WA	99352	BENTON	USA	Oral Diseases and Disorders Research	000	7	4/25/2012	NON-COMPETING CONTINUATION	$377,181
														Subtotal = $377,181

Issue Date FY: 2011 ( Subtotal = $373,234 )
2011	2011	PACIFIC NORTHWEST LAB, DIV OF BATTELLE MEMORIAL INST	POST OFFICE BOX 999	RICHLAND	WA	99352	BENTON	USA	Oral Diseases and Disorders Research	000	6	6/2/2011	NON-COMPETING CONTINUATION	$373,234
														Subtotal = $373,234

Issue Date FY: 2010 ( Subtotal = $387,974 )
2010	2010	PACIFIC NORTHWEST LAB, DIV OF BATTELLE MEMORIAL INST	POST OFFICE BOX 999	RICHLAND	WA	99352	BENTON	USA	Oral Diseases and Disorders Research	000	5	6/1/2010	COMPETING CONTINUATION	$387,974
														Subtotal = $387,974

Issue Date FY: 2008 ( Subtotal = $392,321 )
2008	2008	PACIFIC NORTHWEST LAB, DIV OF BATTELLE MEMORIAL INST	POST OFFICE BOX 999	RICHLAND	WA	99352	BENTON	USA	Telehealth Programs	000	4	4/24/2008	NON-COMPETING CONTINUATION	$392,321
														Subtotal = $392,321

Issue Date FY: 2007 ( Subtotal = $399,275 )
2007	2007	PACIFIC NORTHWEST LAB, DIV OF BATTELLE MEMORIAL INST	POST OFFICE BOX 999	RICHLAND	WA	99352	BENTON	USA	Telehealth Programs	000	3	4/20/2007	NON-COMPETING CONTINUATION	$399,275
														Subtotal = $399,275

Issue Date FY: 2006 ( Subtotal = $404,914 )
2006	2006	PACIFIC NORTHWEST LAB, DIV OF BATTELLE MEMORIAL INST	POST OFFICE BOX 999	RICHLAND	WA	99352	BENTON	USA	Telehealth Programs	000	2	4/12/2006	NON-COMPETING CONTINUATION	$404,914
														Subtotal = $404,914

Issue Date FY: 2005 ( Subtotal = $370,709 )
2005	2005	PACIFIC NORTHWEST LAB, DIV OF BATTELLE MEMORIAL INST	POST OFFICE BOX 999	RICHLAND	WA	99352	BENTON	USA	Telehealth Programs	000	1	4/28/2005	NEW	$370,709
														Subtotal = $370,709

Grand Total All Awards = $7,263,124

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Structural, spatial, and temporal features guiding amelogenins transformation of calcium phosphate into enamel

Award Number: R01DE015347

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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