# Unlocking the biomedical potential of microbial symbionts from complex ecosystems

> **NIH NIH R35** · VIRGINIA POLYTECHNIC INST AND ST UNIV · 2024 · $385,958

## Abstract

Project summary/abstract
New therapeutics are desperately needed for the treatment of diseases with unmet needs, such as emerging
infections and immunological diseases. Specialized metabolites (natural products) produced in nature have
historically played a critical role in drug discovery, however high rates of rediscovery have resulted in a significant
drop in drug candidates. The long-term goal of this proposed research program is to use an ecology-based
discovery platform to investigate complex ecosystems, specifically the microbiota of marine egg masses, where
evolutionary pressures exist to evolve specialized metabolites that can be leveraged as anti-infective and
immunomodulating therapeutics.
The success natural products have had in the clinic is due to their evolutionary history, their structures and
functions evolved over millions of years of selective pressures to carry out an essential role for the producing
organism. For example, many of the antibiotics used in the clinic today are produced by terrestrial
microorganisms that use them to vanquish competitors. The microbiomes of marine egg masses provide an
intriguing source of potential drug candidates as it has been hypothesized that evolutionary pressure has led to
the development of defensive metabolites and these defensive metabolites can be repurposed for the treatment
of infections in humans. Our first long term goal is to establish the egg mass microbiota as a host of diverse
bacterial symbionts and then using these symbionts to build a natural product fraction library. This fraction library
has been screened in a variety of biological assays, with an initial focus on anti-infective and immunomodulating
assays, and the natural products components of each fraction are being profiled with innovative metabolomics
techniques, nuclear magnetic resonance-based MADByTE and mass spectrometry-based GNPS. Active
components will be elucidated, their biosynthetic gene clusters identified, and evaluated in an in vivo rodent
model. Our second goal is to leverage the ability of the isolated microbes to produce novel metabolites as studies
have revealed that only a fraction (< 25%) of the metabolites are produced under typical laboratory conditions.
Using a community-based co-culturing technique and innovative techniques that utilize collected egg masses
will allow us to replicate many of the chemical interactions that occur in the ecological environment, which are
known play an important role in the regulation of these silent metabolites.
Collectively, our proposed research program will broadly impact the field by establishing marine egg masses as
a good source of novel natural products. Studying the small molecules produced by these bacterial symbionts
will lead to the discovery of novel anti-infective agents and has the potential to repopulate the drug pipeline
targeting unmet and increasingly frequent diseases.

## Key facts

- **NIH application ID:** 10817075
- **Project number:** 5R35GM146740-03
- **Recipient organization:** VIRGINIA POLYTECHNIC INST AND ST UNIV
- **Principal Investigator:** Emily Elizabeth Mevers
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $385,958
- **Award type:** 5
- **Project period:** 2022-07-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10817075

## Citation

> US National Institutes of Health, RePORTER application 10817075, Unlocking the biomedical potential of microbial symbionts from complex ecosystems (5R35GM146740-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10817075. Licensed CC0.

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