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  Molecular Mechanisms of Glaucoma; dissecting the roles of cross-linked actin networks.


   Institute of Ageing and Chronic Disease

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  Dr K Hamill, Prof L Paraoan, Dr B McDonagh  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Glaucoma is the second highest cause of blindness in the world. One of the major risk factors for the disorder is a build up of pressure within the eye that is caused by dysfunction of a region of the eye termed the Trabecular Meshwork (TM) through which aqueous normally drains. A change that is commonly associated with glaucoma is the formation of cross-linked actin networks (CLANs,) a higher order actin arrangement formed as a complex polygonal arrangement of spokes and hubs. Specifically, researchers at Liverpool have demonstrated that whereas 25% of TM cells assemble CLANs in young eyes, their incidence increases to more than 50% in the elderly and 75% in glaucoma suggesting that these actin assemblies are age- and disease-associated.

Initial studies investigated CLANs primarily as part of the TM cell stress response, however, recent data has led to an alternate hypothesis where CLANs are associated with long-term cell survival. CLANs are likely to provide mechanical support to cells, aiding their resistance of compression and shearing forces, but in so doing, convey rigidity to otherwise pliable cells.
This PhD will determine the mechanisms, dynamics and processes through which CLANs assemble, will characterize the molecular changes within CLAN forming versus non-forming cells and will test the CLAN-mediated cell-survival hypothesis.

The student undertaking this project will be trained in up-to-date techniques used worldwide in molecular and cellular biology. This will position them very competitively for postdoctoral positions, fellowship funding and/or industry placements. Additionally, the student will learn valuable specific skills such as 3D tissue model preparation and cutting edge microscopy techniques.
Specific skills the student will be trained in will include:
• Microscopy and image analysis – immunofluorescence microscopy, immunohistochemistry, epitope retrieval, live cell imaging, live fluorescent imaging, FRAP.
• Cell Culture – primary and immortalized cell growth, 3D model systems, cloning - mRNA extraction, RT-PCR, primer design, ligation, bacterial transformation and growth, restriction digests for subcloning, site-directed mutagenesis, viral packaging of expression vectors.
• Protein expression and purification –transfection, protein extraction, size exclusion and affinity chromatography.
• Protein analysis – lysate and ECM extract preparation, western immunoblotting, mass spectroscopy.
• Data analysis – statistics, image processing, cell tracking.
• Writing – manuscript preparation, grant proposals, review articles

The Institute of Ageing and Chronic Disease is fully committed to promoting gender equality in all activities. We offer a supportive working environment with flexible family support for all our staff and students and applications for part-time study are encouraged. The Institute holds a silver Athena SWAN award in recognition of on-going commitment to ensuring that the Athena SWAN principles are embedded in its activities and strategic initiatives.


Funding Notes

This is an unfunded project. Students applying are responsible for PhD fees and their own living costs
In addition bench fees at £5000 per year will be required to cover research costs.

Enquiries to Dr Kevin Hamill [Email Address Removed]

To apply please send your CV and a covering letter to [Email Address Removed] with a copy to [Email Address Removed]

Where will I study?