PhD Student - Age-related Macular Degeneration

Age-related macular degeneration (AMD) affects the retina of the eye and is the major cause of blindness in the elderly. AMD exists as dry and wet forms. In health, light-capturing photoreceptor cells in the retina rapidly shed their outer-segments (POS), which are phagocytised by neighbouring retinal pigmental epithelial (RPE) cells. Inefficient phagocytosis by RPE leads to POS accumulation, named drusen, which characterizes dry AMD. Sustained accumulation of drusen characterizes dry AMD, whereas neovascularization features wet AMD. Wet AMD can be successfully treated, but there is no cure for dry AMD, which affects 80-90% of patients. The unmet need for dry AMD therapeutics necessitates a detailed knowledge of the aetiology of dry AMD.
Besides aging, gene variants related to phospholipid phagocytosis and complement pathways contribute to AMD. Recently, also the succinate receptor (SUCNR1) was associated with AMD and SUCNR1 knockout mice developed features similar to dry AMD. Oxidative and endoplasmic reticulum stress induces cellular release of the mitochondrial metabolite succinate and subsequent activation of the SUCNR1. We hypothesize that the SUCNR1 is involved in stress-induced cellular phagocytosis in RPE cells. Using primary and cultured retina cells and patients DNA, the objectives of this highly-translational project are to identify the role of a SUCNR1 miRNA in AMD, characterize genes and pathways regulated by activated SUCNR1 in AMD, determine whether succinate can act as a therapeutic in AMD, and determine the involvement of rare SUCNR1 mutations in early AMD.
The anticipated data will not only reveal the patho-physiological function of the SUCNR1 in the retina for the first time, but will also clarify how the SUCNR1 contributes to AMD development, and whether succinate could be a therapeutic to attenuate AMD development in SUCNR1-deficient patients.
This Radboudumc financed project is a collaboration between the department of Ophthalmology (Prof. A. den Hollander) and Physiology (Prof. PMT Deen). The department of ophthalmology is world-wide recognized as a leading group in the treatment and genetic analysis of AMD patients, whereas the department of Physiology has a strong expertise in molecular, cellular and animal pathophysiology.
In this project, the applicant will work within the dept. Physiology, which is, together with basic science and research-oriented clinical departments of the Radboud University Medical Center, housed in the "Radboud Institute for Molecular Life Sciences (RIMLS, www.rimls.eu)", which integrates diverse scientific expertise in molecular and medical science for the advancement and innovation in translational research.
Major research responsibilities for this position:

• Functional analysis of miRNA binding sites using molecular cloning, cell transfection and cell culture
• Retina and RNA isolation, 습-array analysis, and biochemical pathway analysis
• Genomic genotyping
• Data analysis and interpretation
• Contribution towards preparation and submission of manuscripts
• Presentation of data and communication with research partners

Desired skills and experience

The ideal candidate has:

• A MSc in molecular cell biology or physiology or related field
• A permit to work with animals (art. 9)
• Affinity with and (preferentially) scientific knowledge and expertise with eye-related disorders
• Structured working style
• Good English writing and presentation skills
• A strong motivation, flexibility, and stress-resistance
• The ability to work and interact with others in an energetic and supportive research group

About the employer

What we offer:

• Exciting and innovative project
• Stimulating and productive scientific environment in an international setting.
• Salary and contract is based on research experience and qualifications.

Further information and contact
Salary is according to CAO-RUNMC.
Additional information about the vacancy can be obtained from Prof. Peter MT Deen / Prof. Anneke den Hollander. Detailed information about the department can also be found at www.physiomics.eu.

Applicants should send a letter of intent outlining special interest in the position, overall related qualifications, experience and career goals, a curriculum vitae and names and addresses of professional references.

Please submit your application using the Apply through website.