Wednesday, January 15, 2025 1/15/2025

Investigating structural heterogeneities in amyloid aggregates with multiscale infrared spectroscopic imaging

Award Number: R35GM138162
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 The misfolding and aggregation of specific proteins into fibrillar amyloid deposits is the pathological hallmark of a wide class of diseases and neurodegenerative disorders, which represent a major public health concern worldwide. While it is recognized that amyloid aggregates play an active part in the molecular pathology of the disease, the exact aggregation states that causes cytotoxicity and relationship between pathogenesis and the distribution of secondary structures in amyloid aggregates is not well established. The aim of this project is to investigate the heterogeneities in protein secondary structure in amyloid aggregates both in-vitro and ex-vivo and identify their relationship with disease progression. Our approach relies on utilizing state-of-the-art nanoscale infrared (IR) spectroscopy and confocal IR spectroscopic imaging to map protein secondary structures in amyloid deposits. We will focus on studying amyloid aggregates and their heterogeneities in Alzheimer’s disease (AD) to develop and optimize our methods, and subsequently aim to extend these strategies to investigate amyloid aggregates in other diseases such as Parkinson’s disease and Breast Cancer. The hypothesis underlying this effort is that structural heterogeneities of amyloid deposits, and not just specific fibrillar structures, are correlated with disease progression. We will utilize photothermal AFM-IR, a technique that augments IR spectroscopy with Atomic Force Microscopy, to obtain nanoscale aggregate-specific spectra. Seeded growth from tissue extracts from AD patients will enable probing the differences in aggregation pathways and structural polymorphisms associated with different disease stages. Amyloid aggregates in tissues will be investigated through confocal IR microscopy. The tissue spectral data will be analyzed to classify amyloid deposits based on their secondary structure distributions, and the correlation between distinct classes of deposits and disease stages will be explored. We further aim to integrate AFM-IR and IR microscopy and develop a spatially and spectrally adaptive IR imaging approach that will enable multiscale measurement of spectral data in tissues. The unique aspect of this approach is that it uses cutting edge technologies in spatially resolved IR spectroscopy and imaging to investigate a problem that is central to the molecular pathology of a wide range of diseases and development of therapeutic strategies.


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: 2024 ( Subtotal = $359,659 )
2024	2024	UNIVERSITY OF ALABAMA	801 UNIVERSITY BLVD	TUSCALOOSA	AL	35401	TUSCALOOSA	USA	Biomedical Research and Research Training	000	5	6/14/2024	NON-COMPETING CONTINUATION	$359,659
														Subtotal = $359,659

Issue Date FY: 2023 ( Subtotal = $360,271 )
2023	2023	UNIVERSITY OF ALABAMA	301 ROSE ADMIN BLDG	TUSCALOOSA	AL	35487	TUSCALOOSA	USA	Biomedical Research and Research Training	000	4	6/30/2023	NON-COMPETING CONTINUATION	$360,271
														Subtotal = $360,271

Issue Date FY: 2022 ( Subtotal = $570,353 )
2022	2022	UNIVERSITY OF ALABAMA	301 ROSE ADMIN BLDG	TUSCALOOSA	AL	35487	TUSCALOOSA	USA	Biomedical Research and Research Training	001	3	9/7/2022	SUPPLEMENT FOR EXPANSION	$209,500
2022	2022	UNIVERSITY OF ALABAMA	301 ROSE ADMIN BLDG	TUSCALOOSA	AL	35487	TUSCALOOSA	USA	Biomedical Research and Research Training	000	3	9/6/2022	NON-COMPETING CONTINUATION	$360,853
														Subtotal = $570,353

Issue Date FY: 2021 ( Subtotal = $361,407 )
2021	2021	UNIVERSITY OF ALABAMA	301 ROSE ADMIN BLDG	TUSCALOOSA	AL	35487	TUSCALOOSA	USA	Biomedical Research and Research Training	000	2	6/24/2021	NON-COMPETING CONTINUATION	$361,407
														Subtotal = $361,407

Issue Date FY: 2020 ( Subtotal = $361,936 )
2020	2020	UNIVERSITY OF ALABAMA	301 ROSE ADMIN BLDG	TUSCALOOSA	AL	35487	TUSCALOOSA	USA	Biomedical Research and Research Training	000	1	9/7/2020	NEW	$361,936
														Subtotal = $361,936

Grand Total All Awards = $2,013,626

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Investigating structural heterogeneities in amyloid aggregates with multiscale infrared spectroscopic imaging

Award Number: R35GM138162

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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