# Protein Organelles In Human-Associated Bacteria

> **NIH NIH R35** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $381,626

## Abstract

Project Summary
Cellular compartmentalization is a defining feature of life. Similar to eukaryotes, many prokaryotes
compartmentalize their cytosol to carry out specialized metabolic reactions, prevent toxicity and store nutrients.
However, prokaryotes rely on protein-based organelles instead of membrane-based compartmentalization
strategies. A semipermeable protein shell creates a sequestered reaction space separated from the bulk
cytosol. This compartmentalization can increase the local concentrations of enzymes and metabolites, prevent
the leakage of toxic or volatile intermediates and create unique reaction environments. Protein organelles
enable specialized biochemistry not possible without compartmentalization and have been implicated in carbon
fixation, iron metabolism, nutrient utilization and stress resistance. Protein organelles are present in nearly all
bacterial and archaeal phyla and can be found in many important human pathogens. Protein organelles have
been suggested to enable pathogens to utilize alternative nutrients and withstand the human immune system.
The two main classes of microbial protein organelles are encapsulin nanocompartments (20 to 50 nm) and
bacterial microcompartments (40-500 nm). In both cases specialized enzymatic machinery is selectively
encapsulated within self-assembling protein shells leading to unique catalytic capabilities. The overall goal of
my laboratory is to explore and understand the functional diversity of protein organelles encoded in microbial
genomes and to investigate their contribution towards human health and disease. We will initially prioritize
protein organelles found in human-associated microbes. Hundreds of microbes encode uncharacterized
protein organelle systems, some of which have been shown to contribute to microbial virulence. However, the
molecular and physiological functions of most protein organelle systems have not been explored while their
contributions towards human health and disease are poorly understood. The goals of this proposal are to (1)
carry out a detailed mechanistic and structural analysis of the major classes of protein organelles, (2)
determine how protein organelles contribute towards microbial stress resistance and detoxification and (3)
investigate how protein organelles enable microbes to utilize alternative nutrient sources. Based on our
expertise and pioneering investigations of encapsulin systems, we are uniquely positioned to successfully
pursue the research described in this proposal. We will use a multifaceted approach including biochemistry,
structural biology, microbiology and omics approaches to dissect the molecular mechanisms underlying protein
organelle function and elucidate how these megadalton protein assemblies influence human health and
disease. This information will be essential for exploring future therapeutic approaches aimed at disrupting
protein organelle function to reduce microbial stress resistance and fitness and thus pathogenicity. Th...

## Key facts

- **NIH application ID:** 10000174
- **Project number:** 5R35GM133325-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Tobias Wolfgang Giessen
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $381,626
- **Award type:** 5
- **Project period:** 2019-08-21 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10000174

## Citation

> US National Institutes of Health, RePORTER application 10000174, Protein Organelles In Human-Associated Bacteria (5R35GM133325-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10000174. Licensed CC0.

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