# Computational Studies of the Molecular Basis of Natural and Acquired Resistance to Extremes in Microbes

> **NIH NIH R01** · GEORGETOWN UNIVERSITY · 2022 · $345,345

## Abstract

PROJECT SUMMARY
 Our long-term goal is to understand how microbes are able to withstand remarkable extremes of
temperature, pressure, and chemical composition (P-T-X), by determining how the macromolecular
structures comprising the microbes are preserved. Our focus is on the effects of high pressure, which are
much less understood than those of temperature. Since high-pressure methods are increasingly being used
for food preservation, understanding the effects of pressure is important for human health and welfare.
Disturbingly, some mesophilic microbes appear to able to withstand ~10 kbar pressures, while piezophilic
(pressure-loving) microbes have been found at maximum pressures of ~1.1 kbar. Determining what
pressures will disrupt structures of proteins in cell-like conditions will help to define the limiting pressures
that microbes can grow at.
 Our goal for the proposed work is to understand the interplay of P-T effects on proteins by
examining enzymes from psychrophiles (cold-loving) and thermophiles (hot-loving) that are also piezophilic
at different P-T. Based on our previous work on a piezophilic psychrophile enzyme, microbes may be mainly
adapted for temperature rather than high pressure and enzymes from psychrophiles appear much more
fragile than those from thermophiles. The proposed studies will expand the range of growth temperatures of
the source organisms to piezophilic thermophile enzymes. They will also address the effects of piezolytes,
which are osmolytes that protect against pressure effects, on proteins. Our approach uses molecular
dynamics computer simulations and biophysical experiments.
 Our specific aims are to:
Aim 1. Understand piezophilicity in other psychrophile enzymes.
Aim 2. Understand piezophilicity in thermophile enzymes.
Aim 3. Understand how piezolytes change pressure effects on proteins.

## Key facts

- **NIH application ID:** 10348160
- **Project number:** 5R01GM122441-06
- **Recipient organization:** GEORGETOWN UNIVERSITY
- **Principal Investigator:** JENNIFER A SWIFT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $345,345
- **Award type:** 5
- **Project period:** 2017-01-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10348160

## Citation

> US National Institutes of Health, RePORTER application 10348160, Computational Studies of the Molecular Basis of Natural and Acquired Resistance to Extremes in Microbes (5R01GM122441-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10348160. Licensed CC0.

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