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Synthesis and Exploration of Highly Fluorescent Thiazolothiazole Molecular Sensors for Probing Membrane Potential Dynamics

Award Number: R15GM140392
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: 09/15/2020
PERIOD OF PERFORMANCE END DATE: 01/31/2028

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Synthesis and Exploration of Highly Fluorescent Thiazolothiazole Molecular Sensors for Probing Membrane Potential Dynamics - PROJECT SUMMARY The long-term goal of this project is to understand how highly fluorescent thiazolothiazole molecular sensors are impacted by changing electric fields in cellular membranes. Tracking these changes offers the potential to gain a deep understanding of complex and rapidly changing cellular physiology. Fluorescent, small molecule voltage sensitive dyes (VSDs) have greatly impacted this field, however, there is still a great need to develop new dyes with enhanced long wavelength emission for imaging in thick tissues, improved photostability for long-term imaging, and improved cell membrane voltage sensitivity. In this project, we propose the continued exploration of unique and highly fluorescent thiazolo[5,4-d] thiazole molecular fluorophores. TTz dyes are the next generation of imaging tools because they exhibit high photochemical stability, are easy to prepare/modify, show fast response times, good cell membrane localization, negligible cytotoxicity, and are sensitive to cellular membrane potential. We recently developed a highly improved method to synthetically access asymmetric TTz dyes for cell membrane applications. In addition, we are leveraging new insights into the sensing mechanism of the TTz dyes to design molecular probes with even greater cell membrane potential sensitivity. We will conduct spectroscopic and electrochemical characterizations to understand the role of molecular structure on the cell membrane localization and voltage sensing. We will evaluate the cell membrane voltage sensing performance of the dyes, which will provide important feedback for further tuning of their photophysical properties.


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 = $476,148 )
2025	2025	UNIVERSITY OF NORTH CAROLINA AT CHARLOTTE	9201 UNIVERSITY CITY BLVD	CHARLOTTE	NC	28223	MECKLENBURG	USA	Biomedical Research and Research Training	001	2	1/22/2025	COMPETING CONTINUATION	$476,534
2025	2022	UNIVERSITY OF NORTH CAROLINA AT CHARLOTTE	9201 UNIVERSITY CITY BLVD	CHARLOTTE	NC	28223	MECKLENBURG	USA	Biomedical Research and Research Training	000	1	12/20/2024	SUPPLEMENT FOR EXPANSION	-$386
														Subtotal = $476,148

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	UNIVERSITY OF NORTH CAROLINA AT CHARLOTTE, THE	9201 UNIVERSITY CITY BLVD	CHARLOTTE	NC	28223	MECKLENBURG	USA	Biomedical Research and Research Training	000	1	10/19/2023	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2020	UNIVERSITY OF NORTH CAROLINA AT CHARLOTTE, THE	9201 UNIVERSITY CITY BLVD	CHARLOTTE	NC	28223	MECKLENBURG	USA	Biomedical Research and Research Training	000	1	9/25/2023	NEW	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $99,579 )
2022	2022	UNIVERSITY OF NORTH CAROLINA AT CHARLOTTE, THE	9201 UNIVERSITY CITY BLVD	CHARLOTTE	NC	28223	MECKLENBURG	USA	Biomedical Research and Research Training	000	1	7/19/2022	SUPPLEMENT FOR EXPANSION	$99,579
														Subtotal = $99,579

Issue Date FY: 2020 ( Subtotal = $462,546 )
2020	2020	UNIVERSITY OF NORTH CAROLINA AT CHARLOTTE, THE	9201 UNIVERSITY CITY BLVD	CHARLOTTE	NC	28223	MECKLENBURG	USA	Biomedical Research and Research Training	000	1	9/10/2020	NEW	$462,546
														Subtotal = $462,546

Grand Total All Awards = $1,038,273

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Synthesis and Exploration of Highly Fluorescent Thiazolothiazole Molecular Sensors for Probing Membrane Potential Dynamics

Award Number: R15GM140392

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: 09/15/2020

PERIOD OF PERFORMANCE END DATE: 01/31/2028

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