EASTBIO: Interactions between bacteriophages and mastitis pathogens: understanding their influence on bacterial biology and their potential for exploitation at the University of Edinburgh

Supervisors:  Gavin Paterson, David Gally

Bacteriophages (phages) are viruses that specifically infect bacteria. Straddling the boundary of living and non-living entities these are fascinating to study from the perspective of understanding basic biology. However, they are also important clinically by shaping the evolution of bacterial pathogens with significant consequences for human and veterinary medicine. For instance, phages are a major vehicle for horizontal gene transfer between bacteria, contributing to the spread of genes encoding virulence factors such as toxins or antimicrobial resistance. By contrast, they can also be exploited as novel treatments for bacterial infections, either by using the phages themselves (phage therapy) or their cell-wall lytic enzymes. In the face of growing antibiotic resistance alternative treatments are much-needed and the exploitation of phages is an attractive potential option for this.

This project will investigate the phages of bovine mastitis pathogens with the objectives being to evaluate their contribution to horizontal gene transfer and the potential to exploit them as novel therapies for mastitis.

Mastitis, inflammation of the mammary gland, is one of the most common and economically important diseases in dairy cattle. Bovine mastitis causes reductions in milk yield and quality, and in severe cases the affected animal is culled. As a result, the annual cost of bovine mastitis to the UK dairy industry is estimated to be c. £200m with the worldwide cost projected to be $200bn. Furthermore, bovine mastitis is responsible for the use of large amounts of antimicrobial drugs with concomitant worries over the development and spread of antimicrobial resistance and the impact that this may have on both animal and human medicine. A variety of bacterial species are responsible for bovine mastitis with Escherichia coli, Streptococcus uberis, Staphylococcus aureus and other staphylococci typically being the most prevalent.

Based in the Roslin Institute, the project benefits from world-class facilities with the Easter Bush campus being Europe’s largest concentration of animal science research. The project offers a varied training experience in laboratory microbiology and bioinformatics supported in a collegiate environment. Specific techniques may include; bacterial culture, PCR, phage isolation, electron microscopy, DNA and RNA extraction, cloning, protein expression and genome analysis. There is a vibrant postgraduate community on campus (>150 PhD students) providing a rich diversity of scholarly and networking opportunities.

Phage Therapy for Antibiotic-Resistant Bacterial Infections. Hatfull GF et al. Annu Rev Med. 2021        

Aug 24. doi: 10.1146/annurev-med-080219-122208. Online ahead of print.

Phage-Encoded Endolysins. Abdelrahman F et al. Antibiotics (Basel). 2021 Jan 28;10(2):124. doi: 10.3390/antibiotics10020124.

The Age of Phage: Friend or Foe in the New Dawn of Therapeutic and Biocontrol Applications? Hassan AY et al. Pharmaceuticals (Basel). 2021 Feb 28;14(3):199. doi: 10.3390/ph14030199.

• This 4 year PhD project is part of a competition funded by EASTBIO BBSRC Doctoral Training Partnership (DTP) http://www.eastscotbiodtp.ac.uk/how-apply-0

• EASTBIO Application and Reference Forms can be downloaded via   http://www.eastscotbiodtp.ac.uk/how-apply-0

• Please send your completed EASTBIO Application Form along with a copy of your academic transcripts to [email protected]

• You should also ensure that two references have been send to [email protected]  by the deadline using the EASTBIO Reference Form

This opportunity is open to UK and international students and provides funding covering stipend and UK level tuition fees.  The University of Edinburgh covers the difference between home and international fees meaning that the EASTBIO DTP offers fully-funded studentships to all appointees.

There is a cap on the number of international students the DTP recruits.  It is therefore important for us to know from the outset which fees status category applicants will fall under when applying to our university.

Please refer to UKRI websiteand Annex B of the UKRI Training Grant Terms and Conditionsfor full eligibility criteria.