Project code

PHBM5131023

Applications are invited for a self-funded, 3 year full-time or 6 year part-time PhD project.


The PhD will be based in the School of Pharmacy and Biomedical Science and will be supervised by Dr Robert Baldock. 

The work on this project will:

  • Examine the cellular and molecular impact of fluoroquinolone antibiotics and characterise their impact on mitochondrial function. 
  • Uncover and catalogue the potential DNA repair mechanisms that protect and repair mitochondrial DNA

Antibiotics are the most fundamental tools we have in the fight against bacterial infections. Without these drugs, bacterial infections that could otherwise be easily treatable could become life-threatening, as such it has become essential to ensure that these drugs can continue to be used and remain effective. Recently, a group of antibiotics, known as fluoroquinolones, have been shown to cause number of severe and potentially permanent disabling side-effects in a sub-population of the people who are prescribed them. This has resulted in the use of these highly-effective antibiotics being restricted due to the potential side-effects. Further research has demonstrated that the side-effects of fluoroquinolones result from off-target effects in mitochondria in some patients, though it is unclear why some individuals suffer these side-effects while others do not.

This research aims to establish why some individuals suffer from these severe side-effects by investigating the mechanisms employed by cells to protect their mitochondrial DNA. By understanding this process, it will potentially be possible to screen-out individuals who are likely to suffer these adverse effects before prescribing. Importantly, having this approach would ensure that these drugs can continue to be used safely.

This project will employ mammalian cell culture alongside the establishment of several cell-based assays to examine the cells and the mitochondria via microscopy, flow cytometry and plate-reader based assays. In addition, the mitochondrial DNA copy number will be examined directly using quantitative PCR. Previously, our lab has identified several candidate DNA repair proteins that are part of the mitochondrial proteome (Alkanjari & Baldock, 2021. Bioscience Reports). By examining changes in mitochondrial function of cells depleted of these factors in response to mitotoxic stress, we will determine which proteins contribute to the protection and repair of mitochondrial DNA.  There will also be opportunities for the PhD candidate to develop highly  transferable skills including coding and several bioinformatic methods. 

Associated publications:
Allkanjari K. & Baldock R.A. (2021) Beyond base excision repair: An evolving picture of mitochondrial DNA repair Bioscience Reports, Vol. 41(10): BSR20211320.

 

Fees and Funding

Visit the research subject area page for fees and funding information for this project.
 

 

Entry requirements

You'll need a good first degree from an internationally recognised university (minimum upper second class or equivalent, depending on your chosen course) or a Masters degree in biological/biosciences or a related area. In exceptional cases, we may consider equivalent professional experience and/or qualifications. English language proficiency at a minimum of IELTS band 6.5 with no component score below 6.0.

When you are ready to apply, please follow the 'Apply now' link on the Pharmacy, Pharmacology and Biomedical Sciences PhD subject area page and select the link for the relevant intake. Make sure you submit a personal statement, proof of your degrees and grades, details of two referees, proof of your English language proficiency and an up-to-date CV. Our How to Apply page offers further guidance on the PhD application process.