# Undergraduate Jeffrey Vanegas Research Experience for underrepresented biomedical research students

> **NIH NIH R35** · RICE UNIVERSITY · 2021 · $9,963

## Abstract

Project Summary/Abstract (30 lines of text)
Fungal natural products (NPs) have been a preeminent source of medicine and played pivotal
roles as pharmaceuticals for the treatment of human diseases. The rapid expansion of fungal
genome sequences and the development of bioinformatics tools have enabled the identification
of thousands of fungal NP biosynthetic gene clusters (BGCs), thus providing an unprecedented
opportunity to discover new fungal NPs. However, the discovery of new bioactive fungal NPs
remains challenging, due to difficulties in prioritizing BGCs and genetic manipulations in fungi. In
this proposal, we expect to build pipelines to rapidly discover novel bioactive fungal natural
products that can serve as the next generation of drug candidates for the treatment of human
diseases; to do this, we will apply the CRISPR Cas genome editing technologies and dedicate
these tools to the biosynthesis of fungal natural products. To achieve the research goal, our first
direction will focus on identifying and characterizing rarely discovered ribosomally synthesized
and post-translationally modified peptides (RiPPs) from fungal origins. Due to RiPPs’ unique
biosynthetic machinery, complex chemical characteristics, and important pharmacological
properties, bacterial RiPPs have drawn strong interest from both academia and the
pharmaceutical industry. However, only a handful of RiPPs have been identified from fungi, even
though fungi is known to be a prolific producer of NPs. By characterizing novel biosynthetic
enzymes of known RiPPs and new fungal BGCs identified by bioinformatics analysis, we expect
to greatly broaden and deepen our understanding of the biosynthesis of fungal RiPPs and expand
the repertoire of novel fungal RiPP NPs. Our second direction will focus on expanding and
applying CRISPR-based genome engineering toolkits to characterize biosynthetic gene clusters
from filamentous fungi. CRISPR-Cas tools have been successfully demonstrated to be feasible
in fungal species but are rarely applied in the investigation of fungal NP biosynthesis. We will
develop complementary sets of CRISPR-Cas tools for manipulating fungal biosynthetic gene
clusters in both native and heterologous expression hosts. By doing so, we expect to develop a
full set of CRISPR gene-editing toolkits to rapidly carry out genetic manipulations to study natural
product biosynthesis in filamentous fungi. Together, the two research directions and collaborative
research endeavors through BGC characterization, genetic tool advancement, and new
bioinformatics algorithm development will build a complete pipeline to significantly increase the
repertoire of fungal NPs and analogs, especially fungal RiPPs, making these molecules valuable
drug candidates for human therapeutics.

## Key facts

- **NIH application ID:** 10408899
- **Project number:** 3R35GM138207-02S2
- **Recipient organization:** RICE UNIVERSITY
- **Principal Investigator:** Xue Gao
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $9,963
- **Award type:** 3
- **Project period:** 2020-08-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10408899

## Citation

> US National Institutes of Health, RePORTER application 10408899, Undergraduate Jeffrey Vanegas Research Experience for underrepresented biomedical research students (3R35GM138207-02S2). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10408899. Licensed CC0.

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