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Genetics: How human teeth form and how that process fails in the inherited condition amelogenesis imperfecta


Key facts

Type of research degree
Application deadline
Ongoing deadline
Country eligibility
International (outside UK)
Professor Chris Inglehearn
Additional supervisors
Professor Chris Inglehearn
School of Medicine
Research groups/institutes
Leeds Institute of Medical Research at St James's
<h2 class="heading hide-accessible">Summary</h2>

Amelogenesis is the process of enamel formation and is essential for the development of functional teeth. Amelogenesis imperfecta (AI) is a failure of that process. AI enamel is abnormally thin, soft, fragile, pitted and/or badly discoloured, with poor function and aesthetics, causing patients problems such as early tooth loss, severe embarrassment, eating difficulties and pain. Enamel cannot be regenerated by the human body, making this a life-long, chronic condition. AI affects around 1 in 14,000 in the US, but its prevalence can be much higher in certain populations. To date mutations in 18 genes have been implicated in non-syndromic AI (eg Smith CE et al 2017, EJHG, doi: 10.1038/ejhg.2017.79; Parry DA et al 2016, AJHG 99:984-990), giving rise to X-linked, recessive and dominant patterns of inheritance in families. However these genes account for &amp;lt;50% of cases, raising the question of which genes and mutations are implicated in the remaining patients and what function the encoded proteins have in amelogenesis.<br /> <br />

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

<p>This project will screen new families/cases with AI to find novel genes and mutations; test for possible links with more common tooth conditions such as molar incisor hypomineralisation, caries and fluorosis; image the cells which lay down enamel, the ameloblasts, in normal tooth development and in animal models of AI to see how the disease affects the action of these cells; if possible, the project will also model and study the effect of new mutations using genome editing and, where appropriate, carry out in silico modelling of the effects of specific mutations on the proteins involved.</p> <p>The results of this project will add to the library of AI genes for genetic screening, increasing the success of screening and improving genetic counselling. They will also inform the search for treatment and will improve our understanding of the biology of tooth (and bone) development.</p> <h3>Environment:</h3> <p>The student will be based in the section of Ophthalmology and Neuroscience (OPNE) in collaboration with the Leeds Dental Institute (LDI), School of Medicine, University Of Leeds. The appointed student will have the opportunity to learn and carry out bioinformatics analyses of next generation sequencing, and to study the expression patterns and function of newly implicated genes and proteins using a wide range of molecular and cellular biology techniques. Depending on initial genomic findings, work may progress to tissue culture, confocal microscopy, live cell imaging, transcript analysis, genome editing and protein modelling studies.<br /> &nbsp;</p> <p><strong>In line with the bespoke nature of our International PhD Academy a modified PhD project can be proposed dependent on students interests and background.</strong></p>

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

<p>Please note these are not standalone projects and applicants must apply to the PhD academy directly.</p> <p>Applications can be made at any time. To apply for this project applicants should complete an <a href="">online application form</a> and submit this&nbsp;alongside a full academic CV, degree transcripts (or marks so far if still studying) and degree certificates. Please make it clear in the research information section that you are applying for the International PhD Academy: Medical Research, as well as the title of the project you wish to be considered for.</p> <p>We also require 2 academic references to support your application. Please ask your referees to send these <a href="">references</a> on your behalf, directly to <a href=""></a></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>

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

A degree in biological sciences, dentistry, medicine, midwifery, nursing, psychology or a good honours degree in a subject relevant to the research topic. A Masters degree in a relevant subject may also be required in some areas of the Faculty. For entry requirements for all other research degrees we offer, please contact us.

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

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: &acirc;&euro;&cent; British Council IELTS - score of 7.0 overall, with no element less than 6.5 &acirc;&euro;&cent; TOEFL iBT - overall score of 100 with the listening and reading element no less than 22, writing element no less than 23 and the speaking element no less than 24.

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

<p>Informal enquires about regarding the bespoke taught first year of the PhD programme and research projects can be made by contacting <a></a></p> <p>Enquiries regarding the application process should be directed to the Faculty of Medicine and Health Graduate School&nbsp;Office&nbsp;e: <a href="tel:0113 343 8221"></a> t: +44 (0)113 343 8221.</p>

<h3 class="heading heading--sm">Linked research areas</h3>