Bovine digital dermatitis (BDD) is a severe, infectious, foot skin disease affecting cattle worldwide. This disease causes severe pain resulting in ruminant lameness and impacting animal welfare. BDD results in reduced milk yield and poor reproductive performance which equates to costing the UK dairy industry alone a substantial £74 million/year. Anaerobic, spiral microorganisms of the genus Treponema are considered causal of BDD. There remains no comprehensive, efficacious treatment for BDD and stewardship issues abound over antibiotic use, whilst use of heavy metal or formalin footbathing are environmentally damaging and carcinogenic respectively. This project sets out to identify and characterise both lysogenic and obligately lytic bacteriophage of treponemes and their interaction with these bacteria as they represent potential therapeutic/control agents.
The project is a BBSRC DTP PhD studentship (48 months), with specific objectives as follows:
1. To isolate lysogenic bacteriophage from treponemes within the University of Liverpool (UoL) culture collection and to isolate obligately lytic phage from ruminant foot swabs and farm slurry. We will genome sequence and characterise all isolated bacteriophage, as well as investigating their specificity across a panel of diverse pathogenic and commensal treponemes.
2. To undertake bacteriophage-host co-evolution experiments and undertake comparative genomics to dissect bacteriophage mechanisms of bacterial species specificity.
3. To characterise phage inhibition by treponeme toxin:antitoxin (TA) systems we will generate a TA system knockout mutant treponeme. We will then investigate any differences between mutant and wild type treponeme when exposed to phage to underpin development of robust obligately lytic phage for treatment. We will investigate biochemical interactions of the putative TA systems with the host bacteria.
4. To develop cocktails of lytic bacteriophage capable of targeting the diverse range of treponemal species involved in BDD. Here, using the co-evolution experiments we will produce obligately lytic bacteriophage cocktails with optimum broad specificity. Depending on diversity of lytic phage identified we will either use synthetic biology to adapt specificity of lytic phage or attempt to convert lysogenic phage to obligately lytic phage before investigating efficacy against BDD treponemes.
The above described study should substantially further the understanding of bacteriophage:spirochete interaction as well as resulting in novel treatments beneficial for cattle health. This studentship is BBSRC DTP funded with a substantial training component. The student will undertake laboratory placements at the University of Durham and the Liverpool School of Tropical Medicine as well as a professional internship placement.
HOW TO APPLY
Applications should be made by emailing [Email Address Removed] with:
· a CV (including contact details of at least two academic (or other relevant) referees);
· a covering letter – clearly stating your first choice project, and optionally 2nd ranked project, as well as including whatever additional information you feel is pertinent to your application; you may wish to indicate, for example, why you are particularly interested in the selected project(s) and at the selected University;
· copies of your relevant undergraduate degree transcripts and certificates;
· a copy of your passport (photo page).
A GUIDE TO THE FORMAT REQUIRED FOR THE APPLICATION DOCUMENTS IS AVAILABLE AT https://www.nld-dtp.org.uk/how-apply. Applications not meeting these criteria may be rejected.
In addition to the above items, please email a completed copy of the Additional Details Form (as a Word document) to [Email Address Removed]. A blank copy of this form can be found at: https://www.nld-dtp.org.uk/how-apply.
Informal enquiries may be made to [Email Address Removed]. The closing date for applications is 10th January 2022 at 5.00pm (UK time).
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