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

Project description

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 <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.

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.

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.

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.

Entry requirements

This project is available immediately to both Home/EU rate applicants and International applicants who are able to self-fund their studies. Students must be able to provide the appropriate level of fees based on their fee status plus laboratory consumables costs per year. This is in addition to the provision of personal living expenses.

You should hold a first degree equivalent to at least a UK upper second class honours degree in a relevant subject. 

Candidates 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 minimum requirements are:

• British Council IELTS - score of 6.5 overall, with no element less than 6.0.
• 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.

How to apply

Applications can be made at any time. Potential applicants should initially contact the lead supervisor Professor Chris Inglehearn with informal enquiries about this research project.

To formally apply for this project applicants should complete a Faculty Scholarship Application form 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

We also require 2 academic references to support your application. Please ask your referees to send these references on your behalf, directly by email.

If you have already applied for other scholarships using the Faculty Scholarship Application form you do not need to complete this form again. Instead, you should email to inform us you would like to be considered for this scholarship project.