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Non-image-forming circuits in an in vitro model of the human retina (REF: RDF22/HLS/APP/HILGEN)


   Faculty of Health and Life Sciences

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  Dr Gerrit Hilgen, Dr R Ranson  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

The retina is the light‐sensitive tissue that lines the back of the eyeball. It contains specialised cell types that convert the visual scenery into neuronal signals which are transferred via the optic nerve to the visual areas of the brain. Besides such “image-forming” function, the retina has also an “non-image-forming” function, for example the synchronisation of the circadian rhythm (a rhythm that repeats about every 24 hours and regulates the sleep cycle). Intrinsically photosensitive retinal ganglion cells (ipRGCs) are critical for this synchronisation. In this project, we want to test if retinal organoids (retinas created from cultured human cells) can be used as an in vitro model of the human retina to study “non-image-forming” functions.

Human-induced pluripotent stem cells (hiPSCs) are generated through reprogramming of, for example, skin cells and represent a source for producing a virtually unlimited number of human tissues. In a fruitful collaboration between neuroscience and stem cell science, we generated hiPSCs-derived retinal organoids which recapitulate the architecture of a native human retina and show impressive photoreceptor-driven light-sensitivity (Hallam, Hilgen et al., 2018). Retinal organoids represent a source to produce a virtually unlimited number of human tissues and have been successfully used by us for ocular disease modelling (Buskin et al., 2018), transplantation (Zerti, Hilgen et al., 2021) and drug screening (Dorgau et al, 2021). However, in our papers we describe only the “image-forming” responses, but we also recorded the typical sustained “non-image-forming” responses to strong prolonged light.

To date, no study comprehensively characterised ipRGCs in retinal organoids. The aims of this PhD studentship project are 1) to locate potential ipRGCs in hiPSC-derived retinal organoids and 2) structurally and functionally compare these cells to ipRGCs in the mouse retina.

The project will use immunocytochemistry, cell fillings and confocal microscopy to structurally describe ipRGCs in retinal organoids and compare against mice ipRGCs. Immunostaining with antibodies against ipRGCs, neurotransmitter receptors and ion channels will further characterise the potential use of retinal organoids as a suitable model for pharmacologically motivated research. The project aims also to functionally characterise the ipRGCs in retinal organoids by means of single cell electrophysiology. The outcome of the project would deliver the first comparative study of ipRGCs in retinal organoids and mice. Such knowledge would help to establish retinal organoids as model for circadian rhythm research.

The student will be supervised by Dr Gerrit Hilgen and co-supervised by Dr Rachel Ranson. Dr Hilgen is interested in discovery and translational aspects of biomedical science with a focus on the mature and neonatal retina in health and disease and hiPSC-derived retinal organoids. The project will work closely with the Northumbria Centre for Sleep Research (Prof Malcom von Schantz & Dr Nayantara Santhi), Prof. Majlinda Lako (Retinal Stem Cell Lab Newcastle University) and Prof. Evelyne Sernagor (Retinal Neuroscience Lab Newcastle University). The student will benefit from working with these collaborators and will gain experience in techniques that will produce more impact full outcomes.

Eligibility and How to Apply:

Please note eligibility requirement:

·      Academic excellence of the proposed student i.e. 2:1 (or equivalent GPA from non-UK universities [preference for 1st class honours]); or a Masters (preference for Merit or above); or APEL evidence of substantial practitioner achievement.

·      Appropriate IELTS score, if required.

·      Applicants cannot apply for this funding if currently engaged in Doctoral study at Northumbria or elsewhere or if they have previously been awarded a PhD.

For further details of how to apply, entry requirements and the application form, see

https://www.northumbria.ac.uk/research/postgraduate-research-degrees/how-to-apply/ 

Please note: All applications must include a covering letter (up to 1000 words maximum) including why you are interested in this PhD, a summary of the relevant experience you can bring to this project and of your understanding of this subject area with relevant references (beyond the information already provided in the advert). Applications that do not include the advert reference (e.g. RDF22/…) will not be considered.

Deadline for applications: 18 February 2022

Start Date: 1 October 2022

Northumbria University takes pride in, and values, the quality and diversity of our staff and students. We welcome applications from all members of the community.

Informal enquiries to Dr Gerrit Hilgen ([Email Address Removed]).


Funding Notes

Each studentship supports a full stipend, paid for three years at RCUK rates (for 2021/22 full-time study this is £15,609 per year) and full tuition fees. UK and international (including EU) candidates may apply.
Studentships are available for applicants who wish to study on a part-time basis over 5 years (0.6 FTE, stipend £9,365 per year and full tuition fees) in combination with work or personal responsibilities.
Please also read the full funding notes (https://www.northumbria.ac.uk/research/postgraduate-research-degrees/studentships/rdf) which include advice for international and part-time applicants.

References

Buskin et al., Nat Commun 2018 Oct 12;9(1):4234; Zerti, Hilgen et al., Stem Cells 2021 Jul;39(7):882-896; Dorgau et al., Stem Cells Transl Med 2021 (in press); Hallam, Hilgen et al., Stem Cells 2018 Oct;36(10): 1535-1551
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