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Coiled-coil proteins as drivers of protein assemblies, and recruitment pathways for broadening biomedical participation

Award Number: R01GM157388
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: 07/07/2026
PERIOD OF PERFORMANCE END DATE: 02/28/2031

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Coiled-coil proteins as drivers of protein assemblies, and recruitment pathways for broadening biomedical participation - PROJECT SUMMARY/ABSTRACT Liquid-liquid phase separation (PS) is thought to be the process by which the cell organizes many of its complex structures. While PS is typically associated with intrinsically disordered regions, regions with well-defined structures are also known to contribute, particularly if they can support multivalent transient interactions. Recently, coiled-coil proteins, which can lack elements typically associated with phase separation, have been identified as forming liquid condensates in cells. Examples include structural elements in the centrosome, spindle and Golgi, as well as proteins that help to initiate endocytosis. Motivated by those observations, we recently developed coarse-grained models that demonstrate that the transient interactions between small coiled-coil regions are sufficient to drive phase separation in silico, results which have been supported experimentally by synthetic biology collaborators. Taken together, these observations indicate that coiled-coil regions act as drivers of the intermolecular interactions that organize cells. However, the molecular details of the phase separation of coiled-coil proteins is still unclear. Coiled-coil regions have long confounded structural biology techniques because of their inherent plasticity. We hypothesize that coiled-coil mediated phase separate can arise from exactly those transient interaction that have confounded structural work. We propose phase separation is driven by individual labile coils that interact through their multimeric interfaces, or by interactions between stable and well defined coiled-coil structures and other parts of the protein. We have designed three aims, combining computational (Aim 1), biochemical, and cell biology approaches (Aims 2 and 3) to dissect the molecular mechanisms driving the assembly of condensates by proteins that initiate endocytosis (Aim 2) and organize the Golgi cisternae (Aim 3). Our long term goal is to understand the functional and medical importance of CC domains. In addition, we propose a comprehensive plan to improve the accessibility and quality of the biomedical profes- sional development and research training opportunities for students from historically marginalized populations. We will collaborate with Ft. Lewis College, which serves a significant Native and rural population, and has a relative lack of biomedical research opportunities for students. In addition, strengthening the cultural fluency of CU Boulder researchers will help reduce barriers faced by students coming to a primarily white and well-resourced school. We will (Aim 1) use virtual workshops to bring exposure and access of biomedical research to this community, will (Aim 2) host students for research intensive visits to the Colorado Front Range, and (Aim 3) will work to improve the cultural fluency of CU Boulder researchers to improve the quality of those research experiences.


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 = $537,402 )
2026	2026	THE REGENTS OF THE UNIVERSITY OF COLORADO	3100 MARINE ST STE 481	BOULDER	CO	80303	BOULDER	USA	Biomedical Research and Research Training	000	1	7/6/2026	NEW	$537,402
														Subtotal = $537,402

Grand Total All Awards = $537,402

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Coiled-coil proteins as drivers of protein assemblies, and recruitment pathways for broadening biomedical participation

Award Number: R01GM157388

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: 07/07/2026

PERIOD OF PERFORMANCE END DATE: 02/28/2031

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