# Single molecule studies of the dual-helicase activity of transcription factor TFIIH

> **NIH NIH K22** · UNIVERSITY OF MISSOURI-COLUMBIA · 2022 · $249,000

## Abstract

Project Summary/Abstract
The candidate seeks to acquire additional research and career development training through a plan designed
to address deficiencies in her current expertise. The plan will build on her existing skills and knowledge in the
study of a new system which she will carry with her into the next phase of her career. She will use the
mentored phase of this award to build skills in instrument design, personnel management, and manuscript
development and publication. This training will enable her to acquire the additional skills necessary to transition
to independence and establish a successful research program.
The proposed research will use cutting edge single-molecule and computational techniques to study the
enzymatic activity of the DNA-unwinding complex TFIIH. TFIIH opens DNA for both transcription and DNA
repair, but utilizes two separate helicase domains with distinct mechanisms to do so. The proposal employs a
combination of single-molecule magnetic tweezers studies and molecular dynamics simulations to:
characterize the activity of the individual helicase domains of TFIIH (Aim 1); investigate the impact of the two
helicases on each other in the full TFIIH complex (Aim 2); and explore the differences in DNA preference of the
two helicases and the aspects of DNA structure that lead to dominance of one over the other (Aim 3).
Completion of this research project will contribute to the fields of both transcription and nucleotide excision
repair by elucidating the ways in which TFIIH links these two pathways. The results of the proposed research
will provide a foundation for further studies of TFIIH activity and the factors that influence it, and form the basis
of the candidate's first R01 proposal.
The K22 award will provide the candidate with the opportunity to develop new research skills through additional
training during the mentored phase, which will be funded by the NHLBI Division of Intramural Research. These
skills include construction of a combined magnetic tweezers/single molecule fluorescence microscope,
strategies for the design of DNA substrates for single-molecule experiments, and data analysis methods.
During the mentored phase of the award she will also attend courses and seminars designed to impart
management and teaching skills and supervise a post-baccalaureate trainee. She will attend workshops on
manuscript preparation and build on her current publication record. The training plan also includes career
development activities such as practice job talks, mock interviews, and grant writing workshops. These
activities will provide her with invaluable experience and skills that she will draw on as an independent
investigator.

## Key facts

- **NIH application ID:** 10447713
- **Project number:** 5K22HL142846-03
- **Recipient organization:** UNIVERSITY OF MISSOURI-COLUMBIA
- **Principal Investigator:** Kathleen Maria Mills
- **Activity code:** K22 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $249,000
- **Award type:** 5
- **Project period:** 2020-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10447713

## Citation

> US National Institutes of Health, RePORTER application 10447713, Single molecule studies of the dual-helicase activity of transcription factor TFIIH (5K22HL142846-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10447713. Licensed CC0.

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