# Protein Organelles In Human-Associated Bacteria

> **NIH NIH R35** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $456,894

## Abstract

Subcellular compartmentalization is a fundamental characteristic of life that helps cells to regulate their
metabolism in time and space, carry out specialized metabolic reactions, prevent toxicity, and store nutrients. As
prokaryotes generally do not possess membrane organelles, they have to rely on protein-based approaches to
compartmentalize their cytoplasm. Protein organelles are nano-sized functional analogues of eukaryotic
membrane organelles and utilize a semipermeable protein shell to create a sequestered space separated from
the rest of the cell. This compartmentalization strategy can increase the local concentrations of enzymes and
metabolites, prevent the leakage of toxic or volatile intermediates, and create unique microenvironments with
regard to pH and redox state. Protein organelles enable specialized biochemistry that would not be possible
without compartmentalization. Protein organelles are present in nearly all bacterial and archaeal phyla and can
be found in many important human commensals and pathogens. Protein organelles have been suggested to
increase bacterial stress resistance, allow the utilization of alternative nutrients, and help bacteria to colonize the
human host. The two main classes of microbial protein organelles are encapsulin nanocompartments (20-50 nm)
and bacterial microcompartments (40-200 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. Thousands of commensal and pathogenic bacteria encode encapsulins or BMCs which have been
proposed to increase bacterial fitness and adaptability in dynamic environments. However, the structures,
molecular mechanisms, and physiological functions of most protein organelles have not been explored while
their contributions towards human health and disease are poorly understood. To change this, we will prioritize
four research areas, focusing on protein organelle (1) structure and enzymology, (2) contribution towards stress
resistance, (3) role in nutrient utilization and metabolism, and (4) involvement in secondary metabolite
biosynthesis. We will use a multifaceted strategy relying on biochemistry, structural biology, and microbiology
approaches. Our findings will provide novel biochemical, structural, and physiological insights into the role of
protein-based compartmentalization in bacteria and help elucidate how protein organelles contribute towards the
fitness of both commensal and pathogenic bacteria. This information will be essential for exploring future
therapeutic avenues aimed at disrupting protein organelle function and utilizing protein organelles for biomedical
applications.

## Key facts

- **NIH application ID:** 10836894
- **Project number:** 2R35GM133325-06
- **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:** 2024
- **Award amount:** $456,894
- **Award type:** 2
- **Project period:** 2019-08-21 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10836894

## Citation

> US National Institutes of Health, RePORTER application 10836894, Protein Organelles In Human-Associated Bacteria (2R35GM133325-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10836894. Licensed CC0.

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