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Unified synthesis of diverse bioactive chemical probes

PGR-P-432

Key facts

Type of research degree
PhD
Application deadline
Ongoing deadline
Country eligibility
UK and EU
Funding
Competition funded
Source of funding
Research council
Supervisors
Professor Adam Nelson
Schools
School of Chemistry
Research groups/institutes
Chemical Biology and Medicinal Chemistry
<h2 class="heading hide-accessible">Summary</h2>

Identifying and exploring new biologically-relevant chemical space is a major challenge that is central to both chemical biology and medicinal chemistry. Readily-available chemical probes can dramatically influence the biomedical science that is investigated experimentally. Furthermore, small molecule drugs continue to dominate FDA approvals and our collective ability to treat disease. Yet, identifying new biologically-relevant chemical space is hampered by the uneven exploration of both biology and chemistry. Biologists&amp;rsquo; favourite proteins are largely unchanged for &amp;gt;20 years despite a lack of evidence supporting their particular relevance to disease. Moreover, bioactive small molecule discovery continues to be underpinned by a remarkably narrow reaction toolkit that limits the scaffold diversity of explored chemical space. How, then, can new connections between phenotypes, target proteins and bioactive chemotypes be established to further our understanding of biology and, ultimately, to treat disease? <br /> <br /> This project will focus on the development of a one-pot synthesis of diverse small molecule probes, and their investigation in model biological systems.

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

<p>This proejct will focus on the&nbsp;development of&nbsp;approaches that enable the one-pot synthesis of diverse small molecule probes that are already fully-functionalised for chemical biology studies.&nbsp; Crucially, we have prioritised connective chemistry that lies outside the toolkit that currently dominates molecular discovery to enable probes based on diverse and novel molecular scaffolds to be prepared.&nbsp; The resulting probes will thus reside in novel chemical space; will be armed with diverse electrophilic warheads; and will already be functionalised with clickable alkyne tags.&nbsp;The student&nbsp;will demonstrate that these diverse chemical probes can be harnessed to unlock new regions of biologically-relevant chemical space, and may reveal insights into the molecular basis of cell biology mechanisms.</p> <p>The specific objectives are:</p> <ol type="1"> <li>To identify viable substrate sets for one-pot chemical probe synthesis;</li> <li>To prepare a diverse set of fully-functionalised probes using one-pot connective chemistry</li> <li>To assess the probe set in model biological systems</li> </ol>

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

<p>Formal applications for research degree study should be made online through the&nbsp;<a href="http://www.leeds.ac.uk/rsa/prospective_students/apply/I_want_to_apply.html">University&#39;s website</a>. Please state clearly in the research information section&nbsp;that the research degree you wish to be considered for is&nbsp;&ldquo;Diverse probes for chemical biology&quot; as well as&nbsp;<a href="https://eps.leeds.ac.uk/chemistry/staff/4180/professor-adam-nelson">Professor Adam Nelson</a> as your proposed supervisor.</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>We welcome applications from all suitably-qualified candidates, but UK black and minority ethnic (BME) researchers are currently under-represented in our Postgraduate Research community, and we would therefore particularly encourage applications from UK BME candidates. All scholarships will be awarded on the basis of merit.</em></p>

<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>A competition funded project&nbsp;for 3.5 years. A full standard studentship consists of academic fees (&pound;4,600 in Session 2020/21), together with a maintenance grant (&pound;15,285&nbsp;in Session 2020/21) paid at standard Research Council rates. UK applicants will be eligible for a full award paying tuition fees and maintenance. European Union applicants will be eligible for an award paying tuition fees only, except in exceptional circumstances, or where residency has been established for more than 3 years prior to the start of the course.</p>

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

<p>For further information regarding your application, please contact Doctoral College Admissions by email: <a href="mailto:maps.pgr.admissions@leeds.ac.uk">maps.pgr.admissions@leeds.ac.uk</a> or by&nbsp;telephone: +44 (0)113 343 5057</p> <p>For further information regarding the project, please contact Professor Adam Nelson&nbsp;by email: <a href="mailto:A.S.Nelson@leeds.ac.uk">A.S.Nelson@leeds.ac.uk</a></p>


<h3 class="heading heading--sm">Linked funding opportunities</h3>