# Machinery of the Microbial Mobilome

> **NIH NIH R35** · UNIVERSITY OF CHICAGO · 2023 · $444,325

## Abstract

Project Summary
Mobile genetic elements (MGEs) provide bacterial populations with an accessory genome, the “mobilome,” that
helps them survive antibiotics, phage infections, and other stresses. Understanding the core machinery encoded
by MGEs can help explain how accessory genes flow within a microbiome and can also reveal interesting new
enzymes, often with potential as biotech tools. Furthermore, MGE-encoded enzymes are often simplified or
modified variants of chromosomal machinery that, through comparison, can illuminate the evolution of both.
Mechanistic studies of MGEs have lagged far behind the bioinformatics.
Our work focuses on conserved machinery encoded by two families of staphylococcal MGEs that are of particular
importance to human health: SCCs, which are chromosomal islands implicated in the MRSA epidemic, and
pathogenicity islands. Our ongoing efforts have defined a set of conserved core SCC genes and assigned
biochemical activities to most of them, discovering new enzymes and following the interesting questions they
raised along the way. For example, we have discovered a new group of potentially anti-phage DNA glycosylases
and a new type of primase that raises the question of how it evolved as well as how DNA polymerases are
normally prevented from initiating DNA synthesis de novo. We also found that these MGEs encode helicases
with surprising similarity to the eukaryotic and archaeal MCM helicases, but with interestingly different pathways
for loading the helicase onto DNA at the origin of replication.
In addition to building on the work above, we will broaden our questions to the roles of SCC-encoded machinery
in phage defense, horizontal transfer, and copy number expansion. Recent advances in the field combined with
our biochemical groundwork position us to mechanistically dissect the horizontal transfer of SCCs to new strains.
We will also dissect the mechanism by which antibiotic resistance-carrying SCC elements can form tandem
repeats to increase resistance in response to antibiotic treatment.

## Key facts

- **NIH application ID:** 10631561
- **Project number:** 1R35GM149586-01
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** PHOEBE A RICE
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $444,325
- **Award type:** 1
- **Project period:** 2023-08-01 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10631561

## Citation

> US National Institutes of Health, RePORTER application 10631561, Machinery of the Microbial Mobilome (1R35GM149586-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10631561. Licensed CC0.

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