# Mechanisms and regulation of replication, the cell cycle, gene expression, and horizontal gene transfer in prokaryotes, focusing on Bacillus subtilis

> **NIH NIH R35** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2021 · $719,907

## Abstract

Our long term goals are to understand many of the molecular mechanisms and regulation underlying basic
cellular processes in bacteria. We are particularly interested in the control of DNA replication, cellular
responses to perturbations in replication, environmental sensing and signal transduction, and mechanisms
controlling horizontal gene transfer. Our organism of choice for these studies is the Gram positive bacterium
Bacillus subtilis. There is a wealth of information about B. subtilis. It is easy to grow and manipulate genetically
and is related to several pathogens and environmental bacteria that are less tractable experimentally.
 Horizontal gene transfer (HGT) is the driving force in microbial evolution. It is largely mediated by mobile
genetic elements, including viruses, conjugative plasmids, and integrative and conjugative elements (ICEs,
also known as conjugative transposons). Conjugative elements are well known agents contributing to the
spread of genes for antibiotic resistances, pathogenesis, symbiosis, metabolism, and more.
 Despite the prevalence and importance of ICEs, there are deficiencies in our understanding of these
elements, especially in Gram positive bacteria. Our work will focus on the lifecycle of ICEBs1 in B. subtilis. The
ability to experimentally induce ICEBs1 in >90% of cells in a population and achieve relatively high conjugation
frequencies will allow us to answer previously difficult or unstudied problems fundamental to the ICE lifecycle.
We will also identify and analyze host genes needed for ICE function and study interactions between ICEs and
other mobile elements in cells. We will extend our analyses to Tn916, a widespread ICE involved in the spread
of tetracycline resistance. Our findings should be relevant to the transfer of genes between bacteria growing in
many different environments, including the human microbiome.
 Our work will also focus on several aspects of chromosome dynamics and gene expression. Cells have
multiple mechanisms for regulating the initiation of replication. Cells also have regulatory responses to
perturbations in replication, often called checkpoints, which control gene expression and cell cycle progression.
Coupling gene expression and cell cycle progression to chromosome replication and integrity helps prevent the
generation of cells with defective chromosomes. The coordination of genome duplication with cell cycle
progression is important for cellular differentiation and preventing uncontrolled cell growth. Microbial
pathogenesis often depends on normal bacterial replication and growth in the host.
 We will use a variety of approaches and methodologies, both in vivo and in vitro, to characterize: the
control of replication initiation; regulators of the replication initiator and transcription factor DnaA; and genes
controlled in response to perturbations in replication. Understanding these processes in B. subtilis will provide
insights regarding similar processes and homologous pr...

## Key facts

- **NIH application ID:** 10130548
- **Project number:** 5R35GM122538-05
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** ALAN D GROSSMAN
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $719,907
- **Award type:** 5
- **Project period:** 2017-04-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10130548

## Citation

> US National Institutes of Health, RePORTER application 10130548, Mechanisms and regulation of replication, the cell cycle, gene expression, and horizontal gene transfer in prokaryotes, focusing on Bacillus subtilis (5R35GM122538-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10130548. Licensed CC0.

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