# Developing synthetic chemical biology strategies for biochemical investigations and biomedical applications

> **NIH NIH R35** · UNIVERSITY OF NEBRASKA LINCOLN · 2024 · $371,036

## Abstract

Project Summary
Both naturally occurring and laboratory protein modifications are important fields of research since proteins are
central to virtually every biological process. On one hand, protein post-translational modifications (PTMs) are
essential for proper functioning of an organism and are associated with many diseases. It is of great
significance to study PTMs in order to develop new therapeutic agents. On the other hand, continuing
advances in noncanonical amino acid (ncAA) mutagenesis has provided powerful tools for the manipulation
and study of protein function. This MIRA application seeks to merge investigations on both fronts of these
research areas. The first general area of this MIRA project focuses on the co-translational modification of
protein through genetic code engineering. The long-term goal is to explore innovative strategies for ncAA
mutagenesis through reprogramming the genetic code. Our immediate and unique focus is on reprogramming
codon language with quadruplet codons (Qcodons), although triplet nonsense codons are the predominant
ones used in the field of genetic code expansion. Built on our pioneering efforts on tRNA engineering, we
propose a new direction to improve Qcodon decoding efficiency through the identification and implementation
of recoding signals. The use of recoding signals can also significantly mitigate a major concern over
undesirable readthrough of endogenous stop codons with nonsense suppression-based noncanonical amino
acid (ncAA) mutagenesis in live cell studies. We will also apply a Qcodon-dependent and ncAA-mediated
control strategy to the development of HIV-1 vaccines, which represents a novel direction that was first
demonstrated by my group. Such strategy will also be applied to the generation of vaccines against other
pathogenic viruses or bacteria in the future. The second general area of this MIRA project is to investigate the
role of protein tyrosine O-sulfation (PTS) in mammalian cell biology. Our initial efforts will focus on PTS of
chemokine receptors as the first step of our long-term efforts to study the effects of PTS on receptor signaling
in general. Furthermore, we seek to develop therapeutic agents targeting sulfated receptors. These two
innovative projects have their own goals and significance, but are unified under our expertise in
chemical/synthetic biology and are partially associated with each other. The long-term goal of my laboratory is
not only to develop innovative and meaningful chemical/synthetic biology tools, but also to employ these tools
to gain insights into biomedical processes for the development of novel therapeutics.

## Key facts

- **NIH application ID:** 10885908
- **Project number:** 5R35GM149322-02
- **Recipient organization:** UNIVERSITY OF NEBRASKA LINCOLN
- **Principal Investigator:** Jiantao Guo
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $371,036
- **Award type:** 5
- **Project period:** 2023-07-15 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10885908

## Citation

> US National Institutes of Health, RePORTER application 10885908, Developing synthetic chemical biology strategies for biochemical investigations and biomedical applications (5R35GM149322-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10885908. Licensed CC0.

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