# The Facility for Atomic Mutagenesis

> **NIH NIH R24** · UNIVERSITY OF IOWA · 2020 · $254,311

## Abstract

Ongoing advances in the elucidation of protein structures are leading to the production of large volumes of
high-resolution data, in increasingly native environments. However, especially in the case of transmembrane
proteins, experimental options for high-resolution functional analyses remain limited, and thus the usefulness
of the structures in understanding human neurological diseases likewise remains limited. Moreover, the
structures that are obtained represent single, static snapshots of proteins, although these likely have multiple
conformations of functional significance. Thus, there is a growing need among the ion channel and membrane
biophysics community, which is supported by the NINDS, for reagents that directly report on the functionality
and dynamics of membrane proteins in live cells. An elegant solution to these problems is nonsense
suppression, a method that makes it possible to encode any type of synthetic amino acid at a site of interest
within a protein. These so-called unnatural amino acids can take the form of residues with single atom
substitutions, or side-chains with novel fluorescent properties. Although multiple experimental avenues for the
encoding of unnatural amino acids exist, each is associated with significant technical challenges. As such, this
powerful approach remains inaccessible to most investigators studying molecular neuroscience. In 2014, in
response to numerous inquiries by other investigators, the Ahern lab at the University of Iowa (UI) set out to
simplify the dissemination of acylated orthogonal tRNAs, key components in nonsense suppression, for
experiments involving eukaryotic membrane proteins. To this end, we made improvements to the underlying
chemistry, making it more robust and allowing for the encoding of a more chemically diverse set of amino
acids. In addition, these new reagents display vastly improved stability profiles thus allowing for easy shipping
to laboratories throughout the U.S. With our reagents and guidance, a number of new user groups have
successfully applied this previously difficult approach to a variety of membrane proteins relevant to the NINDS
mission. Overall, these efforts have produced a high-functioning collaborative outreach service, “The Facility
for Atomic Mutagenesis.” This resource will provide broad access to custom reagents for nonsense
suppression, and this facility is able to quickly adapt or design synthetic approaches to meet the interests of an
application by new users. As the technologies become more standardized and our user group expands, we will
scale accordingly, taking advantage of infrastructure present with the UI Carver College of Medicine and local
industrial partners such as Integrated DNA Technologies. These collaborations will ultimately support more
efficient dissemination of these research tools, to answer diverse questions in molecular neuroscience. Their
use will be buoyed by a growing user base, annual training seminars, web-based forums and p...

## Key facts

- **NIH application ID:** 9822162
- **Project number:** 5R24NS104617-03
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Christopher A Ahern
- **Activity code:** R24 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $254,311
- **Award type:** 5
- **Project period:** 2017-12-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9822162

## Citation

> US National Institutes of Health, RePORTER application 9822162, The Facility for Atomic Mutagenesis (5R24NS104617-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9822162. Licensed CC0.

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