Understanding the causes of developmental tooth defects using a high-throughput genomic screening approach

Dental enamel is the hardest tissue in the human body. The process of enamel formation is called amelogenesis, and Amelogenesis imperfecta (AI) is the name given to a set of severe defects of this process which are inherited as Mendelian conditions. AI occurs in up to 1:700 live births and presentation varies with the genetic mutation(s) involved. Over 20 genes have been implicated so far by genetic studies, including many by the Leeds AI group (eg Smith et al 2016, EJHG 11:1565; Parry et al 2016, AJHG 99:984 and many other published papers). Clinical care is complex, demanding on patients and the dental team and requires long-term specialist treatment. Patients have difficulty maintaining oral hygiene, suffer low self-esteem and report an inferior quality-of-life.<br /> <br /> Molar Incisor Hypoplasia (MIH) is another type of enamel defect which is similar to AI but only involves some of the teeth in the adult dentition. Unlike AI it is not a Mendelian condition, but there is evidence of both genetic and environmental contributions to susceptibility. It is common, with frequency ranging from 2.4%-40.2% in different populations. At optimum levels fluoride protects teeth from dental decay. Fluorosis is a third category of dental development abnormality of variable severity. It is largely due to a single environmental cause (excessive fluoride in drinking water) during tooth development, but there is data that supports a genetic susceptibility that may influence the severity of the enamel defects.

<p>This project aims to develop a screen for the genetic regions most frequently mutated in AI patients using Multiple Inversion Probes (MIPS) technology, then test this as a pre-screen on all of the new samples being collected by the Leeds AI group, through their network of collaborators around the world. Those that prove negative will then be tested by whole exome or whole genome next generation sequencing and bioinformatics analysis to find new AI genes, which could then be characterised in cell or animal models. The pathology of new forms of AI will be studied by micro-CT scanning, electron microscopy, immunofluorescence and biochemical analysis. Meanwhile the MIPS pre-screen will be applied to sets of patients with MIH and fluorosis to determine whether the same genes contribute to risk of these much more common dental conditions as well. This project will give the successful applicant the opportunity to train in and use a wide range of molecular genetic, bioinformatic, cell biology and pathology techniques, to publish their work with this highly successful group and to begin a career in dental research.</p>

<p>Applications can be made at any time. To apply for this project applicants should complete a<a href="https://medicinehealth.leeds.ac.uk/downloads/download/129/faculty_graduate_school_-_application_form"> Faculty Application Form</a> and send this alongside a full academic CV, degree transcripts (or marks so far if still studying) and degree certificates to the Faculty Graduate School <a href="mailto:fmhpgradmissions@leeds.ac.uk">fmhpgradmissions@leeds.ac.uk</a></p> <p>We also require 2 academic references to support your application. Please ask your referees to send these <a href="https://medicinehealth.leeds.ac.uk/downloads/download/130/faculty_graduate_school_-_scholarship_reference_form">references</a> on your behalf, directly to <a href="mailto:fmhpgradmissions@leeds.ac.uk">fmhpgradmissions@leeds.ac.uk</a></p> <p>If you have already applied for other projects using the Faculty Application Form this academic session you do not need to complete this form again. Instead you should email&nbsp;<a href="mailto:fmhpgradmissions@leeds.ac.uk">fmhpgradmissions@leeds.ac.uk</a> to inform us you would like to be considered for this project.</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>

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.

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 6.5 overall, with no element less than 6.0 &acirc;&euro;&cent; 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>For further information please contact the Graduate School Office<br /> e: <a href="mailto:fmhpgradmissions@leeds.ac.uk">fmhpgradmissions@leeds.ac.uk</a>, t: +44 (0)113 343 8221.</p>