How molecular and cellular changes in mitochondrial translation cause hearing loss

Perrault syndrome is a rare clinically and genetically heterogeneous autosomal recessive condition. Affected individuals have severe to profound sensorineural hearing loss. This hearing loss can be present at birth or be progressive through childhood. Affected women also have ovarian insufficiency resulting in infertility. Some individuals can be affected by white matter brain disorder (leukoencephalopathy), peripheral neuropathy and intellectual disability.

Over the past ten years our research group and others have identified many different genes that, when altered, can result in Perrault syndrome. These genes are linked to each other in that they lead to mitochondrial dysfunction. Recent work in our team has identified variants in additional genes, not previously linked to Perrault syndrome that that we believe cause this condition through mitochondrial dysfunction.

The student will :

1. use assays in yeast and patient cells to determine the function of the novel Perrault syndrome genes and confirm that they are the cause of this condition.

2. use genome and RNA sequencing to identify new genes that cause Perrault syndrome.

3. develop assays to interpret the pathogenicity of variants causing Perrault syndrome.

4. Develop strategies to understand common pathways leading to Perrault syndrome that will inform therapeutic approaches.

This work will majorly advance our understanding of this complex hearing loss disorder and provide he student will excellent foundations for a career in hearing research and human genomics.

 Entry Requirements:

Applicants are expected to hold (or about to obtain) a minimum of an upper second class undergraduate honours degree (or equivalent) in genomics/genetics. A Masters degree in a relevant subject and/or experience in a genomics laboratory or in industry is desirable. 

For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. You MUST also submit an online application form - choose PhD Genomics.

Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/