Characterization of Actin Dynamics and Photoreceptor Dysfunction in Retinitis Pigmentosa

This is one of five projects being offered in 2017 for one or two three year PhD students available in the Edinburgh Super-Resolution Interdisciplinary Consortium. ESRIC is a centre of excellence for super-resolution microscopy. Utilising expertise in molecular and cellular biology from the MRC Human Genetics Unit (HGU) at the University of Edinburgh and Biophysics from the Institute of Biological Chemistry, Biophysics and Bioengineering within Heriot-Watt University our collaboration enables cutting edge research at the interface of biology and biophotonics. ESRIC houses state-of-the-art imaging technologies alongside molecular and cell biology facilities whilst the ESRIC PhD programme offers the opportunity to gain interdisciplinary experience to address important research questions relevant for normal biology and human disease. As part of the PhD students will attend the Royal Microscopical Society accredited ESRIC summer-school and they will participate in our HGU PhD training programme.

Project description:

Mutations in the Retinitis Pigmentosa GTPase Regulator (RPGR) gene account for 80% of all X-Linked Retinitis Pigmentosa (XLRP), an inherited form of untreatable blindness. RPGR’s role in photoreceptor maintenance is unknown, and no therapeutic targets have been identified. Our previous work suggests RPGR regulates rhodopsin trafficking to photoreceptor outer segments by regulating actin turnover in their connecting cilium.

This PhD project will harbor the technical expertise within the ESRIC community to further define RPGR’s function. Using a range of cilial reagents developed by the Mill lab (MRC HGU), dual-color Stimulated Emission Depletion (STED) microscopy and immuno-electron microscopy will resolve, within 10s of nanometres, actin dynamics and cilial trafficking at the photoreceptor connecting cilia. How this process is perturbed in a novel humanized RPGR/XLRP mouse model will also be examined. This will involve resolving the localization of cargoes (rhodopsin and cone opsins) as well as carriers (Rab8 and IFT) with markers of the actin cytoskeleton. This will pinpoint when and where photoreceptor trafficking defects occur. Live imaging of actin dynamics will be monitored using LifeAct using Total Internal Reflection (TIRF) microscopy (IGMM, ESRIC) to assess RPGR’s role in actin dynamics. These studies will inform on mechanism by which RPGR affects actin turnover dynamics, exploiting super-resolution microscopy to identify novel therapeutic targets for RPGR/XLRP.


How to Apply:

These positions would suit a motivated student who must have obtained a first or upper second class UK BSc honors degree, or equivalent for degrees obtained outside the UK, in molecular biology or a related discipline by September 2017.
Applicants should submit a CV, which includes the contact details of 2 references (including email addresses) and a covering letter (no more than 1000 words), indicating a specific project of interest and why the applicant wishes to join the PhD programme and project to [Email Address Removed] by 26 February.
Applicants must also submit an online application to our PhD programme via the University of Edinburgh degree finder (EUCLID system) following the instructions at:
We will not consider applications that have not been submitted to both [Email Address Removed] and EUCLID by the closing date.
If you have not heard from us by 13 March please consider your application unsuccessful (we will not be able to provide feedback on unsuccessful applications).

Eligibility:

This funded studentship is open only to UK students, or EU students if they have been studying in the UK for the previous 3 years or working in a related discipline in the UK. EU students coming from a discipline related to super-resolution imaging are also eligible to apply.