About the Project
AMD is a degenerative disease that impacts the macula area of the neuroretina and supporting retinal pigment epithelium (RPE). Genetic-environmental interactions, aging and cellular senescence-induced alterations to cellular pathways, metabolism, tissue homeostasis and immune-mediated inflammation are implicated in the pathophysiology of AMD. Autophagy is a central cellular house-keeping function that facilitates disposal of damaged cell organelles and protein aggregates. In the eye, this process is highly active in RPE, and increasing evidence suggests impaired autophagy is associated with altered proteostasis, lipofuscin accumulation, metabolic disruption and the early signs of degeneration. Yet, it remains elusive if the changes in autophagy are a cause or consequence of AMD. Of note, small-molecule compounds capable of stimulating autophagy via regulating mTOR or AMPK signalling pathways have been identified and demonstrate promising efficacy to restore autophagy, suppress immune responses and ameliorate neurodegeneration.
The PhD studentship will test the hypothesis that impairment of autophagy in aging RPE is an early AMD event generating mitochondrial strain and altered metabolic sourcing, together perturbing tissue homeostasis and driving chronic inflammation. Autophagy upregulation via small molecules holds a therapeutic promise to retain the mitochondrial health and regulatory immune function. Using a combination of in vitro and in vivo approaches, this project will examine the hypothesis through (i) determining autophagy-enhancing small molecules in primary and iPSC-derived RPE cells; (ii) defining target genes involved in the metabolic and inflammatory pathways of drug action in RPE by RNA-Seq platforms; and (iii) ascertaining the alterations of RPE autophagy in mouse models of AMD, with in vivo assessment of the small molecules to restore tissue homeostasis.
The PhD student will be based within the Ophthalmology Research Laboratories at the Biomedical Sciences Building. We are the lead centre for Inflammation and Immunotherapeutics within the NIHR Biomedical Research Centre in Ophthalmology at Moorfields Eye Hospital, UCL Institute of Ophthalmology and collaboration with the University of Bristol. Our team has expertise in a range of animal models for ocular diseases, in vivo retinal imaging, Optical Coherence Tomography (OCT) and Focal Electroretinogram (ERG) modalities, Transcriptomics & Bioinformatics, FACS (multi-parameter analysis and cell sorting), Metabolic Extracellular Flux analysis and Confocal cell imaging.
Our group has an established track record of PhD students and this is one of two positions on offer this year. The candidate is expected to start in April 2021 and will be directly supervised by a team consisting of Dr Jian Liu, Professor Andrew Dick and Dr David Copland.
Candidate requirements:Applications are sought from high performing individuals who have a 1st or 2.1 higher degree (or equivalent) in a biomedical or related life sciences discipline. Possession of a relevant master’s degree or research experience would be advantageous but is not expected.
How to apply:Please make an online application for this project at http://www.bris.ac.uk/pg-howtoapply. Please select Faculty of Health Sciences and Translation Health PhD on the Programme Choice page. You will be prompted to enter details of the studentship in the Funding and Research Details sections of the form.
For general enquiries linked to the online application process, please email email@example.com
Further information:For informal enquiries or further information about this PhD project, please contact Dr Jian Liu (firstname.lastname@example.org).
Closing Date: 5pm, 26th February
students. International/EU applicants may apply if they can fund the difference in fees which is currently £18,835 per year. The studentship also includes a research consumables allowance. Standard University of Bristol eligibility criteria apply.
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