See below for details;
PhD Studentship: Dissecting the Role of LaNts and their Receptors in Epidermal Wound Healing and Squamous Cell Carcinoma.
Stipend: £13,863 pa
Institute of Ageing and Chronic Disease, Department of Eye and Vision Science
Location: Liverpool
Project starting date: 1 December 2014
Closing date for applications: Friday 27 June 2014
Eligibility: UK or EU citizens only
Supervisors: Dr Kevin J Hamill and Professor Colin Willoughby
Research Project
All forms of tissue remodelling, including wound repair and tumour cell invasion, requires coordinated modification to the extracellular matrix (ECM), the cytoskeleton and to cell-matrix interactions. Expanding our fundamental understanding of epidermal wound repair and squamous cell cancer invasion and
metastasis is a critical step to identifying new therapeutic strategies in these areas. This project will
investigate the roles of a recently identified family of small, secreted proteins, which our preliminary data strongly implicate as being important regulators of both these processes. These proteins, termed LaNts, structurally resemble a family of extracellular signalling molecules, the netrins, which have defined roles in the regulation of cell migration during nerve growth, organogenesis and tumourigenesis. By analogy, we hypothesise that the LaNts may be the skin equivalent of the netrins. This studentship is designed to characterise the role of the LaNts and netrin receptors in skin biology with particular emphasis on the regulation of keratinocyte motility, proliferation and invasion. The work is split into two connected parts. In the first, the LaNt receptors will be identified, the signalling cascades modulated by them characterised and the phentoypic consequences of those signalling events will be dissected in cell lines derived from normal and SCC sources. In the second part, the student will approach the same questions from the side of the netrin receptors. Through a combination of knockdown and rescue experiments each receptor expressed by keratinocytes will be investigated for its contribution to wound repair, tumour invasion and metastasis. The data garnered in these cell culture and 3D tissue equivalent based assays will provide the launch point for future in vivo experiments and, in the longer term, for therapeutic development.
The student undertaking this project will develop expertise in core molecular and cellular biology techniques and also learn valuable skills in the use of complex model systems and cutting edge microscopy techniques and therefore will become extremely competitive for future academic or industry positions.
This project will be primarily supervised by Dr Kevin J Hamill, a lecturer in the Institute of Ageing and Chronic Disease at the University of Liverpool with additional supervision from Professor Colin Willoughby.
The Institute of Ageing and Chronic Disease and its constituent departments are fully committed to promoting gender equality in all activities. In recruiting researchers and academic staff we stress the supportive nature of the working environment and the flexible family support that the University provides. The Institute has recently been awarded a bronze Athena SWAN award in recognition of on-going commitment to ensuring that the Athena SWAN principles are embedded in its activities and strategic initiatives.
References
- Hamill KJ, Langbein L, Jones JC, McLean WH. Identification of a novel family of laminin N-terminal alternate splice isoforms: structural and functional characterization. J. Biol Chem, (2009) 284:35588-96.
- Hamill KJ, Kligys K, Hopkinson SB, Jones JC Laminins: Complex Molecules with complex assembly States. J Cell Sci, (2009) 122:4409-17
- Hamill KJ, Hopkinson SB, Hoover P, Todorovic V, Green KJ, and Jones JC. Fibronectin expression determines skin cell motile behavior. J Invest Dermatol (2012) 132, 448-457.
- Hopkinson SB, DeBiase PJ, Kligys K, Hamill K, Jones JC. Fluorescently tagged laminin subunits facilitate analyses of the properties, assembly and processing of laminins in live and fixed lung epithelial cells and keratinocytes. Matrix Biol, (2008) 7, 640-7
Funding Notes
This project is supported by a three-year award from the British Skin Foundation which covers annual UK fees and a stipend at the Research Council UK rate. Consideration will be given to overseas applicants who have additional funding to make up the difference in fee rates.
For further details or for an informal discussion please contact Dr Kevin Hamill khamill@liverpool.ac.uk
Interviews are expected to be held around 10 July. To apply for this opportunity please send your CV and covering letter by email to Dr Kevin Hamill khamill@liverpool.ac.uk with a copy to iacdpgr@liv.ac.uk
LaNts and Laminins 
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