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Directing Biomolecular Phase Behavior with Enzyme-Responsive Elastin-Like Polypeptides (ELPs)

Award Number: R35GM166109
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: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 04/30/2031

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Directing Biomolecular Phase Behavior with Enzyme-Responsive Elastin-Like Polypeptides (ELPs) - PROJECT SUMMARY/ABSTRACT My lab engineers biopolymers—the building blocks of life—to develop stimuli-responsive biomaterials and advance fundamental understanding in soft matter and polymer physics. Biopolymers with stimuli-responsive phase behavior have expanded the frontiers of health technologies including regenerative tissue engineering, controlled drug delivery, and scalable production of therapeutic biomolecules. Stimuli-responsive biomaterials are commonly triggered using heat, light, or pH changes. However, these triggers are not always compatible with biological systems: most organisms and cells require tightly regulated temperatures to survive, biomolecules can degrade upon exposure to heat or pH changes, and light can be difficult to administer to biological fluids and tissues. The proposed research in this MIRA application circumvents these challenges by engineering biopolymers with enzyme-responsive phase behavior. These biomaterials will leverage enzymes as biologically encoded stimuli to provide local, dynamic control of phase behavior without requiring changes in the system’s natural temperature, pH, ionic strength, or other factors. This work builds upon my lab’s pioneering design of enzyme-responsive elastin-like polypeptides (ELPs) that form coacervate phases upon isothermal cleavage by proteolytic enzymes, also known as proteases. Protease-responsive ELPs are modular and tunable to respond to different proteases, which enables their development as a platform technology for general medicine and disease treatments. The proposed research will broaden enzyme-responsive ELP functions to direct versatile and robust biomolecular phase transformations. Key research themes will investigate logic-gated control of phase behavior, enzyme-activated assembly of extended-release therapeutic biomaterials, and intracellular regulation of biomolecular condensation processes. This work leverages our expertise in the modular design of functional biomolecules, scalable production of recombinant proteins, and biophysical characterization of stimuli- responsive biomaterials. We will determine sequence–property–function relationships for enzyme-responsive ELPs by integrating methods across recombinant protein engineering, spectroscopy and scattering of proteins in solution, and imaging of self-assembled protein biomaterials. Ultimately, my research program aims to engineer enzyme-responsive ELPs as next-generation biopolymers that direct biomolecular phase behavior. Success of this proposal will yield novel enzyme-responsive ELPs that are activated by specific biochemical conditions, enzyme-driven micelle-to-coacervate phase transformations that allow biomaterials to protect and control the release of therapeutic biologics, and biophysical insights into biomolecular condensation processes that are implicated in human diseases.


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: 2026 ( Subtotal = $364,910 )
2026	2026	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Biomedical Research and Research Training	000	1	8/17/2026	NEW	$364,910
														Subtotal = $364,910

Grand Total All Awards = $364,910

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Directing Biomolecular Phase Behavior with Enzyme-Responsive Elastin-Like Polypeptides (ELPs)

Award Number: R35GM166109

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: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 04/30/2031

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