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Structure and behaviour of magnetic enzymes.


Key facts

Type of research degree
Application deadline
Ongoing deadline
Country eligibility
International (open to all nationalities, including the UK)
Source of funding
University of Leeds
Dr Andrew Burnett and Dr Timothy Moorsom
Additional supervisors
Dr Sarah Harris
School of Chemical and Process Engineering
<h2 class="heading hide-accessible">Summary</h2>

This project will investigate how magnetic fields influence the behaviour of complex magnetic molecules using experimental and modelling techniques.<br /> <br /> Molecular magnets are complex molecular systems that can exhibit ferromagnetic behaviour. The huge variety of magnetic molecular systems that have been synthesised, and the complexity of their interactions, means that they can exhibit a range of exotic and tuneable magnetic behaviours that are relevant to a range of technologies. In addition, many magnetic molecules play important biological functions. Molecules that have active sites containing two or more coupled magnetic ions can be made to change their symmetry in response to magnetic fields, due to spin-crossover and charge transfer effects. A key example of this behaviour is the magnetic enzyme Urease, which metabolises urea into ammonia, and is a leading cause of stomach ulcers and stomach cancer. While it is well known that the magnetic state of the active site of Urease is important in this reaction, the mechanism for this is not understood. It is also not clear whether magnetic fields might be able to influence the activity of Urease, and other bioactive magnetic molecules. This project will use a combination of Density Functional Theory and advanced magnetometry to investigate the structure of magnetic molecules, including Urease, in strong magnetic fields and investigate how this alters their activity. The successful student will be trained in the use of cutting edge modelling techniques to uncover the mechanism by which magnetic fields can influence the structure of magnetic molecules, pairing this with experiments in the multi-disciplinary Bragg centre which will uncover new routes toward magnetic therapies that take advantage of these effects. <br />

<h2 class="heading hide-accessible">Full description</h2>

<p style="margin-bottom:8px; text-align:justify">Jack Bean Urease is a unique metal dependent enzyme which plays an important role in hydrolysis of urea to ammonia. [1] Controlling the hydrolysis of urea can inhibit the growth of H. Pylori bacteria in the stomach, which is a class 1 carcinogen associated with the formation of peptic ulcers and gastric cancer. [2] Urea hydrolysis involves the binding of the molecule to a nickel ion in one of six active sites in the urease enzyme. Each active site contains two nickel ions bridged by a hydroxide ion. [3] Due to the presence of magnetic ions in this enzyme and their critical role in the hydrolysis reaction, there have been several attempts to perform magnetic characterization on crystalline Jack Bean Urease (JBU) which have determined that binding of urea to the active site is accompanied by a change in paramagnetic susceptibility due to the different role of high and low spin Ni sites in the reaction. [4]</p> <p style="margin-bottom:8px; text-align:justify">This project will expand on initial work, where we have observed a blocking like transition in the crystalline JBU, and vibrational modes which become Raman active in a magnetic field. The successful candidate will learn cutting edge methods for simulating the behaviour of the Urease active site using DFT, in particular, learning to simulate the effects of different spin states on the structure and vibrational spectrum of the molecule. They will combine this with cutting edge magnetometry and spectroscopy techniques, to experimentally confirm theoretical predictions. Finally, they will assist in designing and building a reaction chamber within a high field magnet, with which they will study the effects of large magnetic fields on the reactivity of Urease and related magnetic molecules. We anticipate that, in the long term, this work might inform whether magnetic therapies are possible, whereby the behaviour of this enzyme and its carcinogenic risk can be mitigated using magnetic fields.</p> <p>[1] H L T Mobley, Helicobacter pylori: Physiology and Genetics, Chapter 16, pg 179 &ndash; 188, ASM Press, 2001.</p> <p>[2] H L T Mobley et al, Microbiol Rev, 59, 451-480, 1995.</p> <p>[3] A Balasubramanian et al, Jour Mol Bio, 400, 3, 2010.</p> <p>[4] M G Finnega et al, J Am Chem Soc, 113, 10, 1991.</p>

<h2 class="heading">How to apply</h2>

<p>Formal applications for research degree study should be made online through the&nbsp;<a href="">University&#39;s website</a>. Please state clearly in the Planned Course of Study section that you are applying for PhD Chemical &amp; Process Engineering, in the research information section&nbsp;that the research degree you wish to be considered for is <em><strong>Structure and behaviour of magnetic enzymes</strong></em> as well as&nbsp;<a href="">Dr Timothy Moorsom</a>&nbsp;as your proposed supervisor&nbsp;and in the finance section, please state clearly&nbsp;<em><strong>the funding that you are applying for, if you are self-funding or externally sponsored</strong></em>.</p> <p>If English is not your first language, you must provide evidence that you meet the University&#39;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 on an ongoing basis. &nbsp;Potential applicants are strongly encouraged to contact the supervisors for an informal discussion before making a formal application. &nbsp;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 3 April 2024 for Leeds Opportunity Research Scholarship or 8 April 2024 for Leeds Doctoral Scholarship:</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>

<h2 class="heading heading--sm">Entry requirements</h2>

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.

<h2 class="heading heading--sm">English language requirements</h2>

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.

<h2 class="heading">Funding on offer</h2>

<p><strong>Self-Funded or externally sponsored students are welcome to apply.</strong></p> <p><strong>UK</strong>&nbsp;&ndash;&nbsp;The&nbsp;<a href="">Leeds Doctoral Scholarships</a>&nbsp;and&nbsp;<a href="">Leeds Opportunity Research Scholarship</a>&nbsp;are available to UK applicants. &nbsp;<a href="">Alumni Bursary</a>&nbsp;is available to graduates of the University of Leeds.</p> <p><strong>Non-UK</strong>&nbsp;&ndash; &nbsp;The&nbsp;<a href="">China Scholarship Council - University of Leeds Scholarship</a>&nbsp;is available to nationals of China (open from October 2023). The&nbsp;<a href="">Leeds Marshall Scholarship</a>&nbsp;is available to support US citizens.&nbsp;<a href="">Alumni Bursary</a>&nbsp;is available to graduates of the University of Leeds.</p> <p><strong>Important:&nbsp;</strong>&nbsp;Any costs associated with your arrival at the University of Leeds to start your PhD including flights, immigration health surcharge/medical insurance and Visa costs are&nbsp;<strong>not</strong>&nbsp;covered under these studentships.</p> <p>Please refer to the&nbsp;<a href="">UKCISA</a>&nbsp;website for information regarding Fee Status for Non-UK Nationals.</p>

<h2 class="heading">Contact details</h2>

<p>For further information about this project, please contact Dr Timothy Moorsom<br /> e:&nbsp;<a href=""></a></p> <p>For further information about your application, please contact Doctoral College Admissions<br /> e:&nbsp;<a href=""></a></p>