Small-molecule Biosensors for Therapeutic Drug Monitoring (TDM)

Small molecule drugs, such as antibiotics, are instrumental in today’s healthcare and many treatments rely on drugs being correctly dosed. Therapeutic drug monitoring is the practice of measuring drug concentrations and adjusting dosing to improve clinical outcomes, reduce or eliminate side effects, and, in the case of antibiotics, reduce the likelihood of Antimicrobial Resistance (AMR) which is now one of the main global challenges.<br /> <br /> In recent years, AMR caused well over a million deaths per year, more than those from HIV/AIDS or malaria, and another 5 million where AMR played a role.[1] This death-toll is predicted to increase significantly over the next decades if the problem is not addressed. One of the drivers of the increase in AMR is the often incorrect dosing of antibiotics – and the current strategy to suppress AMR is to limit use, rather than improve use. <br /> <br /> Therapeutic drug monitoring (TDM) is already best practice for some antibiotics to reduce toxicity, but is not used for many other antibiotics, and not at all to combat AMR. Measuring small molecules is difficult – the current gold-standard technique for measuring small molecules in patient samples is through high-performance liquid chromatography-coupled tandem mass spectrometry (HPLC-MS/MS), which an expensive and highly specialist laboratory tool. Despite being a highly sensitive and accurate method, HPLC-MS/MS is not feasible for TDM in most clinical settings due to the high costs associated with setting up and running these facilities, as well as logistical difficulties in transferring and measuring samples in the required timeframes. <br /> <br /> Over the last few years our group of multidisciplinary researchers at the University of Leeds have developed a new approach for rapid and sensitive detection of small molecule drugs. Our group is keen to broaden the scope of the molecular targets that we can measure and taking the developed diagnostic tests through to clinical use.<br /> <br /> In this fully-funded PhD project you will develop novel biosensors for detecting small molecules which can be used for TDM to personalise treatment, reduce side effects, and combat AMR.<br /> <br /> [1] Murray et al Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis (https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02724-0/fulltext)

<p>Small molecules play a crucial role in modern medicine. These compounds are often the active ingredients in many pharmaceuticals, providing treatment for a wide range of diseases. Their small size allows for efficient absorption, distribution, and metabolism within the body, making them highly effective in therapeutic applications. However, it would often be desirable to measuring drug concentrations and adjusting dosing to improve clinical outcomes – this is generally referred to as therapeutic drug monitoring. But the small size of the drug makes them challenging to be detected with many of the widely used diagnostics methods.</p> <p>Therapeutic drug monitoring (TDM) is essential in ensuring the safe and effective use of small molecule drugs. By measuring drug concentrations in a patient's blood at designated intervals, TDM helps to optimize dosage, minimize side effects, prevent toxicity, and in the case of infections and antibiotics treatment, prevent antimicrobial resistance (AMR). This personalized approach to medication management is particularly important for drugs with narrow therapeutic windows, where the difference between an effective dose and a toxic dose is small. Overall, TDM enhances patient outcomes by tailoring treatment to individual needs, ensuring that each patient receives the most appropriate and effective therapy.</p> <p>An example where TDM is important is when treating infections with antibiotics. In most cases, antibiotics are given in one-size-fits-all doses, but patients, particularly the critically ill, often show significant pharmacological variability, which results in different blood drug levels despite equal dosing. Too high a blood concentration can lead to toxicity, and too low a blood concentration will likely lead to antimicrobial resistance (AMR), which results in infections that are difficult to treat with antibiotics, and more likely to be fatal. Improving the way we dose antibiotics can improve outcomes, reduce side effects and reduce the risk of AMR.</p> <p>We have developed a new way of measuring small molecules which would allow TDM to be used for many more patients. In this PhD project you will build on our previous developments to develop small molecule biosensors to be used for antibiotic TDM when treating infections, for cancer drug TDM, or TDM for monitoring immunosuppressants after, for example, organ transplants.</p> <p>You will be based in the <a href="https://estates.leeds.ac.uk/portfolio-item/sir-william-henry-bragg-building/">Sir William Henry Bragg Building</a> (<a href="https://estates.leeds.ac.uk/portfolio-item/sir-william-henry-bragg-building/">https://estates.leeds.ac.uk/portfolio-item/sir-william-henry-bragg-building/</a>) at the University of Leeds. Our building, which hosts our bio-nanotechnology research facility, was opened in 2020. You will benefit from a diverse and engaging training programmme and will have access to state-of-the-art laboratories, including high-speed atomic force microscopy, rapid prototyping facilities, a wide range of biophysical characterisation tools, patch clamp amplifiers, as well as molecular biology laboratories. You will be part of the Bionano supergroup which includes 20+ academics, 50+ PhD students and 20+ PDRAs working at the interface of biological and medical sciences and nanotechnology. It is a vibrant community that hosts seminars, organises a range of social activities, and enjoys access to a dedicated communal space.</p> <p>We are excited to be working with you. Please contact us (<a href="mailto:c.walti@leeds.ac.uk">c.walti@leeds.ac.uk</a>) to discuss the position more in details.</p>

<p>Formal applications for research degree study should be made online through the <a href="https://www.leeds.ac.uk/research-applying/doc/applying-research-degrees">University's website</a>. Please state clearly in the Planned Course of Study section that you are applying for <em><strong>EPSRC DTP Engineering & Physical Sciences</strong></em> and in the research information section that the research degree you wish to be considered for is <em><strong>Small-molecule Biosensors for Therapeutic Drug Monitoring (TDM)</strong></em> as well as <a href="https://eps.leeds.ac.uk/electronic-engineering/staff/335/professor-christoph-walti">Professor Christoph Walti</a> and <a href="https://medicinehealth.leeds.ac.uk/medicine/staff/737/dr-jonathan-sandoe">Dr Jonathan Sandoe</a> as your proposed supervisor. <em><strong>Please state clearly in the Finance Section that the funding source you are applying for is EPSRC Doctoral Landscape Award 2025/26:  Electronic & Electrical Engineering.</strong></em></p> <p>If English is not your first language, you must provide evidence that you meet the University's minimum English language requirements (below).</p> <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. Across all Faculties 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></p> <p>Applications will be considered after the closing date.  Potential applicants are strongly encouraged to contact the supervisors for an informal discussion before making a formal application. We also advise that you apply at the earliest opportunity as the application and selection process may close early, should we receive a sufficient number of applications or that a suitable candidate is appointed.</p> <p>Please note that you must provide the following documents in support of your application by the closing date of Friday 31 January 2025:</p> <ul> <li>Full Transcripts of all degree study or if in final year of study, full transcripts to date</li> <li>Personal Statement outlining your interest in the project</li> <li>CV</li> </ul>

Applicants to research degree programmes should normally have at least a first class or an upper second class British Bachelors Honours degree (or equivalent) in an appropriate discipline. The criteria for entry for some research degrees may be higher, for example, several faculties, also require a Masters degree. Applicants are advised to check with the relevant School prior to making an application. Applicants who are uncertain about the requirements for a particular research degree are advised to contact the School or Graduate School prior to making an application.

The minimum English language entry requirement for research postgraduate research study is an IELTS of 6.0 overall with at least 5.5 in each component (reading, writing, listening and speaking) or equivalent. The test must be dated within two years of the start date of the course in order to be valid. Some schools and faculties have a higher requirement.

<p class="MsoNoSpacing">A highly competitive EPSRC Doctoral Landscape Award providing full academic fees, together with a tax-free maintenance grant at the standard UKRI rate (£19,237 in academic session 2024/25) for 3.5 years.  Training and support will also be provided.</p> <p>This opportunity is open to all applicants.  All candidates will be placed into the EPSRC Doctoral Landscape Award Competition and selection is based on academic merit.</p> <p><strong>Important:</strong> Please note that that the award does <em><strong>not </strong></em>cover the costs associated with moving to the UK.  All such costs (<a href="https://www.leeds.ac.uk/international-visas-immigration/doc/applying-student-visa">visa, Immigration Health Surcharge</a>, flights etc) would have to be met by yourself, or you will need to find an alternative funding source. </p> <p class="MsoNoSpacing">Please refer to the <a href="https://www.ukcisa.org.uk/">UKCISA</a> website for information regarding Fee Status for Non-UK Nationals.</p>

<p>For further information about this project, please contact Professor Christoph Walti by email to <a href="mailto:C.Walti@leeds.ac.uk">C.Walti@leeds.ac.uk</a></p> <p>For further information about your application, please contact PGR Admissions by email to <a href="mailto:phd@engineering.leeds.ac.uk">phd@engineering.leeds.ac.uk</a></p>