Epigenetic mechanisms controlling stem cells and regeneration in the ear

Prof. Andrea Streit, Craniofacial Development and Stem Cell Biology, King's College London
Prof. Clive Long, Boehringer Ingelheim

Project Description

In the ear, the cochlea is responsible for sound perception. It houses special sensory cells, called hair cells, that transform mechanical energy created by sound waves into electrical signals, which are relayed to the brain by the auditory nerve. Hearing is crucial for navigating our environment as well as for communication with others. Thus, losing the ability to hear impinges on many aspects of daily life, and many people are affected: about one in every 500 children is born with hearing impairment, and more than 50% of adults over 60 suffer from some form of deafness. Hearing loss is caused by genetic mutations, but can also be induced by noise, drugs like antibiotics or cancer drugs or trauma, and many of these affect the structure or function of sensory hair cells. In mammals including humans, once destroyed hair cells cannot regenerate thus leading to permanent hearing loss.


It has recently been discovered that in mice hair cells can regenerate within the first week after birth, but this ability declines rapidly thereafter. Why is this capacity is lost in the ageing cochlea? The Streit group has recently discovered that modulating epigenetic factors prolongs the ability of cochlear supporting cells to replace hair cells after damage. Thus, epigenetic changes may lock ageing supporting cells in a ‘non-regenerative’ state. The aim of this project is to identify and characterise epigenetic modifiers that promote HC regeneration in the ageing ear, to develop new tools to manipulate their function and to understand the underlying molecular events.


Specifically, the student will first analyse the expression of already identified candidate epigenetic modifiers in the mammalian ear, under normal and regenerative conditions. Using existing transcriptomic data s/he will then build predictive networks to model genetic interactions and identify the best candidates for further study. Next, the student will use gain- and loss-of-function approaches to examine the role of candidate factors during regeneration and maintenance of stem cell potential in the ear, and then together with experts in Boehringer Ingelheim develop new tools to manipulate their function. Finally, to understand the molecular mechanisms by which these epigenetic factors act, the student will employ state-of-the-art next generation sequencing approaches and bioinformatics analysis.


The student will benefit from a multidisciplinary team that combines modern ear biology, regeneration of ageing cells and epigenetics, with state-of-the-art data and systems analysis, and structural design of new chemical tools. This will equip the student with unique skills in science in a versatile environment. The student will join an international department with a vibrant research community and the opportunity of many collaborations. King’s College London offers many training opportunities in project-specific and transferrable skills, while Boehringer’s Research Beyond Borders team provides unique experience of research in the pharmaceutical industry. The studentship offers an attractive stipend of £19,000 per annum, travel funds to attend international conferences, and an industrial placement at Boehringer Ingelheim, Germany, of at least three months.

Whole mount preparation of the sensory epithelium of a mammalian cochlea: hair cells stained with phalloidin (green).

Application

Interested applicants are encouraged to contact Prof. Andrea Streit (andrea.streit@kcl.ac.uk) in advance of the deadline.

Closing date is 19th January. Please ensure that you read the Guidelines before submitting an application. Your application and supporting documents should be sent in a single email to LIDo.Admissions@ucl.ac.uk

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