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Staff Profile

Dr Charles Winterhalter

Wellcome Trust Early Career Fellow

  • Email: charles.winterhalter@ncl.ac.uk
  • Telephone: 0191 208 7702
  • Address: Biosciences Institute
    Centre for Bacterial Cell Biology, R.2.04
    Baddiley-Clark building
    Richardson Road
    Newcastle University
    NE2 4AX
Background

I am a Wellcome Trust Early-Career Fellow working on bacterial DNA damage repair mechanisms at the Centre for Bacterial Cell Biology (Faculty of Medical Sciences / Biosciences Institute). My lab specialises in deciphering the DNA repair mechanisms enabling the human pathogen Staphylococcus aureus to survive DNA damage.


S. aureus is the leading Gram-positive bacterium causing death from bacterial infections worldwide and is becoming increasingly resistant to our last-resort antibiotics. Treatment with several classes of antibiotics leads to generation of reactive oxygen species causing DNA damage such as single- and double-strand DNA breaks, and these damages can lead to cell death if not repaired. However, bacteria can evade DNA damage and at present, we lack a full understanding of the critical repair pathways underpinning this process.


Our lab aims to uncover the full repertoire of essential proteins involved in DNA repair in S. aureus and to determine the critical interactions leading to DNA damage repair. Driven by fundamental science, we also investigate the requirement of repair pathways for virulence and their potential to be targeted by small molecule inhibitors. In the future, these essential repair processes could serve as efficient targets for alternative antimicrobial drug development.


Academic background

  • PhD in Synthetic Biology, “A Unified Platform for Experimental and Computational Biology” (University of Newcastle, UK)
  • Master of Science, Systems and Synthetic Biology (University of Evry, France & University of Nottingham, UK)
  • Maitrise of Science, Bioengineering and Computer Science (University of Evry, France)
  • Bachelor of Science, Biological Sciences (University Henri Poincare/University of Evry, France)


List of publications on Google Scholar: Click here.

Research

Following a postdoctoral position specialising in the characterisation of bacterial DNA replication initiation in the model organism Bacillus subtilis (https://doi.org/10.1093/nar/gkad277 and https://doi.org/10.1093/nar/gkac1060), I identified a lack of methodology to investigate unique replication restart events in live cells. Therefore, I established a novel method to enable these studies using the CrispR-Cas system (manuscript in preparation). This novel targeted DNA damage approach can be used to introduce one single or double-strand break at a defined position on the bacterial chromosome, with advantages spanning beyond the study of DNA replication processes.


To establish my own lab, I used this method to identify several novel proteins essential for DNA repair in the model organism B. subtilis and discovered critical discrepancies in our understanding of damage repair pathways. To investigate these processes in a clinically-relevant and critical human pathogen, I adapted this targeted DNA damage approach to study DNA repair in the related bacterium Staphylococcus aureus. Importantly, my preliminary data showed that homologs of Bacillus proteins are also indispensable for DNA repair in S. aureus, and that their inactivation could sensitise antibiotic resistant strains to low levels of DNA damage. My lab now specialises in characterising the role of these critical DNA damage repair processes in S. aureus in the context of lab growth conditions and during infection.

Publications