Exploring the impact of 'hidden' antibiotic resistance

Antibiotics make possible the treatment of life-threatening infections and have added over a decade to average human lifespan. Unfortunately, the utility of these drugs is being eroded as bacteria evolve to resist their effects; in 2019, antimicrobial resistance (AMR) is reported to have killed ~1.3 million people worldwide.

<p>This figure may represent the tip of the iceberg. There is a growing recognition that AMR can exist in forms not detectable using approaches currently employed in the routine diagnostic laboratory; these include heteroresistance (Andersson et al. [2019] Nat Rev Microbiol, 17: 479), and a phenomenon first defined in the O&rsquo;Neill lab called SARM (&lsquo;silencing of antibiotic resistance by mutation&rsquo;)(Kime et al. [2019] mBio, 10: e01755-19). Such &lsquo;hidden&rsquo; resistance (HR) mechanisms are known to occur in clinical isolates, and isolated reports directly link them with treatment failure. However, it is not known to what extent these are compromising antibacterial chemotherapy in patients generally. To explore this, we will recover isolates from patients failing antibiotic treatment and subject these to comprehensive phenotypic/ genetic analysis - including whole genome sequencing - to detect and characterize HR mechanisms, thereby gaining insight into the overall prevalence of HR and the nature/ relative importance of the different mechanistic types. &nbsp;</p> <p>Understanding the impact of HR will be vital to optimally address the global challenges of infection and AMR, and the knowledge gained in this study could be rapidly translated into improved diagnosis and treatment pathways. The project offers an exciting research experience at the basic/ clinical science boundary, and will provide the appointed student with cutting-edge, multidisciplinary training.</p> <h5>References</h5> <ol> <li>Andersson, D. I., Nicoloff, H. &amp; Hjort, K. (2019) Mechanisms and clinical relevance of bacterial heteroresistance. Nat Rev Microbiol 17, 479-496, doi:10.1038/s41579-019-0218-1.2. Kime, L. et al. (2019) Transient Silencing of Antibiotic Resistance by Mutation Represents a Significant Potential Source of Unanticipated Therapeutic Failure. mBio 10, doi:10.1128/mBio.01755-19.&nbsp;</li> </ol> <p><strong>To support the application process or if you want to know more about our non-clinical PhDs a recording of our 2023 webinar can be found via the links below</strong></p> <p><strong>**The deadline dates in the webinar are out of date but are correct in the stand-alone slide deck**</strong></p> <p><a href="https://www.findaphd.com/common/clickCount.aspx?theid=164726&amp;type=184&amp;DID=757&amp;url=https%3a%2f%2fwww.youtube.com%2fwatch%3fv%3djRE-3RqlCh8" rel="nofollow" target="_blank">NIHR Leeds BRC Non Clinical PhD Scheme webinar - YouTube</a></p> <p>with a copy of the slide deck used at</p> <p><a href="https://www.findaphd.com/common/clickCount.aspx?theid=164726&amp;type=184&amp;DID=757&amp;url=https%3a%2f%2fwww.youtube.com%2fwatch%3fv%3dQqQ5PbEdj-8" rel="nofollow" target="_blank">Leeds BRC Non Clinical PhD Webinar FINAL updated slide deck March 24 - YouTube</a></p>

<p>To apply for this scholarship opportunity applicants should complete an <a href="https://biologicalsciences.leeds.ac.uk/research-degrees/doc/how-to-apply">online application form</a> and attach the following documentation to support their application.&nbsp;</p> <ul> <li>Three supporting statements detailing your previous achievements, why you wish to study for a PhD and your experience of using evidence to inform conclusions.&nbsp;These will be used by our shortlisting panel (without any other information you submit) to select candidates for interview. Please<strong> <a href="https://leeds365-my.sharepoint.com/:w:/g/personal/msjsar_leeds_ac_uk/EWpNioRfOnFOtYy0-vI3NMYB-U55N_vtiRXW0VOLS5irwA?rtime=rXynDPvh20g">download</a></strong><a href="https://leeds365-my.sharepoint.com/:w:/g/personal/msjsar_leeds_ac_uk/EWpNioRfOnFOtYy0-vI3NMYB-U55N_vtiRXW0VOLS5irwA?rtime=rXynDPvh20g"> a copy of the template for these statements here</a> and upload it with your application.</li> <li>a full Narrative CV using the <a href="https://leeds365-my.sharepoint.com/:w:/g/personal/msjsar_leeds_ac_uk/ESUuMXUAMQFJplLJWCJumiUBMrjvsU60E0YA0CbF6GZFJQ?e=CV5PTC&amp;wdLOR=c146CB828-59A6-4C09-ABA5-05B1BDE31ED7">NIHR Leeds BRC template</a> &ndash;&nbsp;Please note other versions of CV&rsquo;s will not be accepted.</li> <li>degree certificate and transcripts of marks at both Undergraduate and Postgraduate level as appropriate, or marks so far if still studying</li> <li>Evidence that you meet the University&#39;s minimum English language requirements (if applicable)</li> <li>An <a href="https://app.onlinesurveys.jisc.ac.uk/s/leeds/nihr-leeds-brc-academy-edi-survey">Equality, Diversity and Inclusion questionnaire.</a> We encourage candidates to complete this form so that we can understand our progress in recruiting under-represented groups. It is important to note that all responses are anonymous and data would only ever be used in aggregate to avoid identification of individuals. The questionnaire includes a &lsquo;prefer not to say&rsquo; option against each question if required. The information you provide on this questionnaire will not be used in the shortlisting process.</li> </ul> <p>To help us identify that you are applying for this scholarship project please ensure you provide the following information on your application form;</p> <ul> <li>Select PhD in Medicine as your programme of study</li> <li>Give the full project title and name the supervisors listed in this advert &ndash;&nbsp;Please note you can apply for up to 2 projects. Please list these in order of preference on your applocation form.</li> <li>For source of funding please state you are applying for an NIHR Leeds BRC Non-Clinical Scholarship</li> </ul> <p><em>As an international research-intensive university, we welcome students from all walks of life and from across the world. We foster an inclusive environment where all can flourish and prosper, and we are proud of our strong commitment to student education. &nbsp;Within the Faculty of Medicine and Health we are dedicated to diversifying our community and we welcome the unique contributions that individuals can bring, and particularly encourage applications from, but not limited to Black, Asian, people who belong to a minority ethnic community, people who identify as LGBT+; and people with disabilities. Applicants will always be selected based on merit and ability.</em>&nbsp;</p>

A degree in biological sciences, dentistry, medicine, midwifery, nursing, psychology or a good honours degree (2:1 or above) in a subject relevant to the research topic. A Masters degree is desirable but not essential.

Applicants whose first language is not English must provide evidence that their English language is sufficient to meet the specific demands of their study. The Faculty of Medicine and Health minimum requirements in IELTS and TOEFL tests for PhD, MSc, MPhil, MD are: &bull; British Council IELTS - score of 6.5 overall, with no element less than 6.0 &bull; TOEFL iBT - overall score of 92 with the listening and reading element no less than 21, writing element no less than 22 and the speaking element no less than 23.

<p>The University of Leeds is providing generous matched funding, supplementing the NIHR Leeds BRC award, to allow us to appoint one further non-clinical PhD Fellow who can select from 18 BRC related projects. Each PhD will be registered at the University of Leeds and we welcome applications from individuals, irrespective of their background, who can evidence great potential and commitment.</p> <p>The&nbsp;scholarship will provide academic&nbsp;fees at the UK rate, as well as a&nbsp;stipend of &pound;18,622 (based on the 2023/24 stipend rate, pro-rata for part time study) for up to three years (full time study, five years part time) and is available for&nbsp;UK applicants&nbsp;only. Due to limited funding we can only consider applicants eligible to pay academic fees at the UK fee rate.</p>

<p>For further information about this project please contact Professor Alex O&rsquo;Neill</p> <p>e:&nbsp;<a href="mailto:a.j.oneill@leeds.ac.uk">A.J.ONeill@leeds.ac.uk</a></p> <p>For further information please contact the Faculty Admissions Team<br /> e:&nbsp;<a href="mailto:fmhpgradmissions@leeds.ac.uk">fmhpgradmissions@leeds.ac.uk</a>,&nbsp;</p>