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Genetics: Genome and transcriptome sequencing and functional analysis to find new mutation types in patients with inherited blindness


Key facts

Type of research degree
Application deadline
Ongoing deadline
Country eligibility
International (outside UK)
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>

Human inherited retinal dystrophies (IRDs) result from mutations in over 200 different genes, many of them first implicated by the Leeds Vision Research Group (eg Panagiotou E et al 2017, AJHG 100:960-968; El-Asrag M et al 2015, 96:948-54). By comparison with other inherited human conditions they are relatively well understood. Genetic approaches have implicated defects in several well characterised pathways, including phototransduction, cilia formation, pre-mRNA splicing and the recycling of the 11-cis-retinal chromophore. Screening the known genes solves between 50 and 70% of cases, a remarkably high success rate for such a genetically heterogeneous condition. However, it is likely that the common IRD genes have now been found. Further significant improvement in screening success rate is therefore dependent on improving our ability to detect new classes of mutations, present in known genes, which are being missed by existing screening protocols.

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

<p>This project will use massively parallel sequencing and cutting edge bioinformatics to identify new variants implicated in human retinal diseases, particularly targeting those classes of mutations that are missed or poorly detected by exome screening. To identify these classes of mutation we will use WGS on pre-screened, unsolved cases recruited through Leeds ophthalmic genetics clinics. Cases from other consortia with which the Leeds Vision Research Group collaborates (BRIDGE-SPEED, 100,000 Genomes project, European Retinal Degeneration Consortium) will also be included in the analysis. RNAseq on blood will also be used in selected cases to determine whether this pinpoints a splicing defect or other mechanism in a known IRD gene in a proportion of unsolved cases. Potential causative variants highlighted in these analyses will be subjected to functional testing as appropriate, depending on the nature of the variant and protein and the level of information available in the existing literature.</p> <p>Environment:<br /> The student will be based in the section of Ophthalmology and Neuroscience (OPNE), School of Medicine, University Of Leeds. The appointed student will have the opportunity to learn and carry out bioinformatics analyses of next generation sequencing, both genome and transcriptome, and to study the expression patterns and function of the implicated genes and proteins using a wide range of molecular and cellular biology techniques. Depending on initial findings, work may progress to tissue culture, confocal microscopy, live cell imaging, transcript analysis, genome editing and protein modelling studies.</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>