Tuesday, August 19, 2025 8/19/2025

Directed evolution of broadly fungible biosensors

Award Number: R01GM146093
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: 01/05/2023
PERIOD OF PERFORMANCE END DATE: 11/30/2026

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Directed evolution of broadly fungible biosensors - Abstract The development of new protein biosensors has for the most part been dependent on finding a protein that is already responsive to a known effector. While rational design and directed evolution methods exist for altering the effector specificity of transcription factors, these methods are in general complex and slow, and have failed to solve the more general problem of identifying new protein biosensors at will. In particular, it is often difficult to find a receptor that is both sensitive and specific for a given end product or intermediate, and even when efforts to generate new sensors are successful, they generally recognize effectors that are structurally quite similar to their natural counterparts. In particular, for virtually all industrially and medically useful terpenes there exists no corresponding biosensor. We now propose to develop a combined computational and directed evolution method that should allow us to proceed from any of a wide variety of ‘generalist’ repressors to create highly sensitive and specific biosensors for a structurally diverse range of terpenes and terpenoids for which no biosensors are currently known. To this end, we have developed a novel directed evolution method for altering biosensor specificities, and propose to synergize these with powerful machine learning tools for improving protein function. Extensive Preliminary Results show that the TetR family of transcription factors can be readily manipulated to take on new effector specificities, and that machine learning can be used to improve the function of a wide variety of proteins. We now further propose to identify semi-specific transcription factors as starting points for biosensor design and evolution (Aim 1); use neural network approaches to predict new sensor specificities (Aim 2); and refine these predictions via directed evolution and high-throughput screening (Aim 3).


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 = $314,487 )
2025	2025	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Biomedical Research and Research Training	001	3	8/13/2025	NON-COMPETING CONTINUATION	$31,449
2025	2025	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Biomedical Research and Research Training	000	3	11/25/2024	NON-COMPETING CONTINUATION	$283,038
														Subtotal = $314,487

Issue Date FY: 2024 ( Subtotal = $314,487 )
2024	2024	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Biomedical Research and Research Training	001	2	6/10/2024	NON-COMPETING CONTINUATION	$31,449
2024	2024	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Biomedical Research and Research Training	000	2	11/10/2023	NON-COMPETING CONTINUATION	$283,038
														Subtotal = $314,487

Issue Date FY: 2023 ( Subtotal = $314,487 )
2023	2023	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Biomedical Research and Research Training	000	1	12/28/2022	NEW	$314,487
														Subtotal = $314,487

Grand Total All Awards = $943,461

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Directed evolution of broadly fungible biosensors

Award Number: R01GM146093

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: 01/05/2023

PERIOD OF PERFORMANCE END DATE: 11/30/2026

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