Optimising phage cocktails for treatment of drug resistant pathogens associated with cystic fibrosis. MRC GW4 BioMed2 DTP PhD studentship 2023/24 Entry, PhD in Biosciences. Ref: 4509
About the award
The GW4 BioMed2 MRC DTP is offering up to 20 funded studentships across a range of biomedical disciplines, with a start date of October 2023
These four-year studentships provide funding for fees and stipend at the rate set by the UK Research Councils, as well as other research training and support costs, and are available to UK, EU and International students.
About the GW4 BioMed2 Doctoral Training Partnership
The partnership brings together the Universities of Bath, Bristol, Cardiff (lead) and Exeter to develop the next generation of biomedical researchers. Students will have access to the combined research strengths, training expertise and resources of the four research-intensive universities, with opportunities to participate in interdisciplinary and 'team science'. The DTP already has over 90 studentships over 6 cohorts in it’s first phase., along with 20 students in it’s second phase.
The 84 projects available for application, are aligned to the following themes;
Applications open on 2nd September 2022 and close at 5.00pm on 2nd November 2022.
Studentships will be 4 years full time or up to 8 years part-time.
Dr Remy Chait, Biosciences, Exeter
Prof Ben Temperton, Biosciences, Exeter.
Prof Eshwar Mahenthiralingam, Biosciences, Cardiff
Phage cocktails promise treatments for antibiotic-resistant infections but are arbitrarily composed. They do not account for phage cross-resistance (resistance to one phage confers resistance to others), especially alongside antibiotics or immune responses. Using new high-throughput phage resistance assays and genomics the student will deliver phage cocktails that avoid cross-resistance and maximise effect in combination
with antibiotics and innate host immunity.
Enhanced phage therapy offers a powerful tool to complement existing antibiotics and develop next generation, targeted antimicrobials to combat the global threat of antibiotic resistance. Adjunctive phage- antibiotic combinations can re-sensitize resistant bacteria to antibiotics, block emerging resistance and control resistant infections. In chronic, resistant infections such as those associated with cystic fibrosis, phage therapy offers new hope for cheap and effective treatments. Notably, phages are often combined into cocktails, with the assumption that evolving resistance to multiple phages is less likely than to single phages. However, resistance to one phage may confer resistance to another (e.g., if phages are closely related or share a host receptor), thus truncating the therapeutic lifetime of a cocktail. The rules governing phage cross-resistance are poorly understood as current laboratory methods are unable to evaluate the combinatorial explosion beyond the simplest phage cocktails. Impacts of adding pressures such as antibiotics or host immune response on phage cross-resistance also remain untested, highlighting critical gaps in knowledge needed to optimise phage cocktails for clinical use. We have developed a novel, high- throughput swim assay for evaluating phage resistance and cross- resistance. Briefly, thin channels containing low-concentration nutrient agar are point-inoculated with motile bacteria, which grow and swim along the resulting nutrient gradients. In their path, up to four ‘phage checkpoints’ are placed, each containing one or more phages. As the migrating bacteria pass through a checkpoint, susceptible hosts are killed and resistant hosts continue to the next checkpoint. Hundreds of channels are monitored and imaged every few minutes, yielding time- lapse videos that capture the kinetics of growth, killing and emergence of resistance (https://youtu.be/8pN7RVsNDfs). Bacteria can be sampled on each side of a checkpoint and sequenced to determine genetic mechanisms of resistance. Agar can be supplemented with antibiotics to evaluate how combined selection pressures alter the rules governing resistance. Using these assays, we recently showed that cross-resistance to phages infecting Pseudomonas aeruginosa can be asymmetric (i.e. resistance to Phage A provides resistance to Phage B, but not vice versa), highlighting the complexity of cocktail design and suggesting that specific sequential, rather than simultaneous, applications of phages may extend the lifetime and efficacy of therapeutic phage cocktails. In this project, the student will use high-throughput assays to determine rules of phage cross-resistance for clinical Burkholderia spp. and P. aeruginosa isolated from cystic fibrosis patients.
The student will leverage a collection of hundreds of fully characterised phages and a large number of pathogens held by the supervisory team (>1500 Burkholderia spp. strains (>500 genome sequenced); >100 genomically characterised P. aeruginosa). Combining laboratory work with image processing and bioinformatics, the student will (1) Evaluate the genetics of cross-resistance and determine if we can use sequence data to predict cross-resistance and design better cocktails; (2) Identify frequencies of asymmetric cross-resistance and whether successional application of phage improves treatment robustness; (3) Test whether adjunctive antibiotics alter patterns of cross-resistance; (4) Test impacts of selection pressure from an innate host immune response on cross-resistance using fluorescent bacterial hosts within a Galleria mellonella larva model.
The project offers outstanding interdisciplinary training opportunities in MRC priority skills including quantitative image analysis, statistics, informatics and non-vertebrate alternatives to in vivo studies. The student will integrate within both the Citizen Phage Library (Exeter), and a CF Trust Strategic Research Centre developing novel therapeutics
This studentship is funded through GW4BioMed2 MRC Doctoral Training Partnership. It consists of UK tuition fees, as well as a Doctoral Stipend matching UK Research Council National Minimum (£17,688 p.a. for 2022/23, updated each year), a Research & Training Support Grant (RTSG) valued between £2-5k per year and a £300 annual travel and conference grant based on a 4 year, full-time studentship.
Part-time study is also available and these funding arrangements will be adjusted pro-rata for part-time studentships. Throughout the duration of the studentship, there will be opportunities to apply to the Flexible Funding Supplement for additional support to engage in high-cost training opportunities.
The GW4 BioMed2 MRC DTP studentships are available to UK and International applicants. Following Brexit, the UKRI now classifies EU students as international. The GW4 partners have all agreed to cover the difference in costs between home and international tuition fees. This means that international candidates will not be expected to cover this cost and will be fully funded, but need to be aware that they will be required to cover the cost of their student visa, healthcare surcharge and other costs of moving to the UK to do a PhD.
All studentships will be competitively awarded and there is a limit to the number of International students that we can accept into our programme (up to 30% cap across our partners per annum).
If you are applying for a place on a collaborative programme of doctoral training provided by Cardiff University and other universities, research organisations and/or partners please be aware that your personal data will be used and disclosed for the purposes set out below.
Your personal data will always be processed in accordance with the General Data Protection Regulations of 2018. Cardiff University (“University”) will remain a data controller for the personal data it holds, and other universities, research organisations and/or partners (“HEIs”) may also become data controllers for the relevant personal data they receive as a result of their participation in the collaborative programme of doctoral training (“Programme”).
For further information regarding data protection for the Application Process and if you become a student on one of the Programmes please click here.
For an overview of the MRC GW4 BioMed programme please see the website www.gw4biomed.ac.uk
Applicants for a studentship must have obtained, or be about to obtain, a UK degree, or the equivalent qualification gained outside the UK, in an appropriate area of medical sciences, computing, mathematics or the physical sciences. Please check the entry requirements of the home institution for each project of interest before completing an application. Academic qualifications are considered alongside significant relevant non-academic experience.
English Language Requirements
If English is not your first language you will need to meet the English language requirements of the university that will host your PhD by the start of the programme. This will be at least 6.5 in IELTS or an acceptable equivalent. Please refer to the relevant university for further information. Please refer to the English Language requirements web page for further information.
How to apply
Applications open 2nd September and close at 17:00 on 2nd November 2022
To begin a GW4 BioMed MRC DTP studentship, applicants must secure an offer of funding from the DTP.
Stage 1: Applying to the DTP for and Offer of Funding
1. Select your projects from the project descriptions available on this website. You may select up to two projects in your application. If you are applying for the ICASE project you must choose this as your first choice project and is only open to UK citizens as indicated on the website.
2. Submit your application using this online form before 5 pm on Wednesday, 2nd November 2022.
3. Student shortlisting is conducted in a blind review of studentship applications by theme-specific panels. Up to 60 top candidates who emerge from this deliberation will be invited to interview.
4. Informal, virtual meetings will be arranged by the successfully shortlisted candidates with the lead supervisors of each project to which they have applied before the formal interview.
5. Formal interviews will occur virtually by theme-specific panels including representatives from each GW4 institution on 25-26 of January 2023.
6. Student selection for up to 20 funded studentships occurs after the formal interviews. Projects are allocated based on the rank of the successful candidates, therefore, it is not always possible to offer an applicant their first-choice project.
7. A clearing period will follow until approximately mid-March until all places have been offered and accepted. For this reason, it is not possible to provide immediate interview results to shortlisted applicants.
Stage 2: Applying to the lead institution for an Offer of Study
Once you have been offered a studentship with the GW4 BioMed MRC DTP, you will need to apply for an Offer of a Place at the home institution of your lead supervisor. Please note that each institution has different application processes.
Applicants for projects based at the University of Exeter should apply to the DTP first to secure an offer of funding. Once an offer of funding is issued by the DTP, you will receive more information on submitting a formal application to the relevant institution, guided by the DTP and local admin contacts.
Your online application forms will be evaluated against the following criteria:
Proven academic quality: normally evidenced by an excellent performance to first degree and/or Master’s level but may also be demonstrated by a record of relevant professional practice.
Research potential: evidenced through their supporting statement and supported by performance in research projects at first degree and/or Master’s level, or another form of dedicated preparation for research.
Personal motivation & commitment: evidenced through their supporting statement, by their enthusiasm for the project area and how they see it relating to their career goals.
Non-biomedical disciplines: In line with supporting interdisciplinary and quantitative skills, special consideration will be given by the interview panels to non-biomedical applicants. Such candidates should not feel the selection criteria are biased towards biomedical applicants as their unique skills will be taken into account.
Candidates selected to interview will be evaluated against the following criteria:
Critical thinking assessed via discussion of a student-selected piece of data
Fit with the project: The interview panel will evaluate the candidate’s aptitude and understanding of the key issues in the project, supported by feedback from informal meetings with the potential lead supervisor.
Personal commitment & motivation
If you have any queries about the GW4 BioMed MRC DTP or about applying for an Offer of Funding, you can get in touch with the DTP Team by emailing GW4BioMed@cardiff.ac.uk.
If you have any questions about applying for an Offer to Study, you can get in touch with the administrative team at your home institution:
|Application deadline:||2nd November 2022|
|Value:||Stipend matching UK Research Council National Minimum (£17,688 p.a. for 2022/23, updated each year) plus UK/Home tuition fees|
|Duration of award:||per year|
|Contact: PGR Admissions Officefirstname.lastname@example.org|