LaNts in wound repair, stem cell activation and squamous cell carcinoma
The Laminin N terminus proteins (LaNts) are a relatively unstudied protein family that are related to netrins and laminins. To date there are only two publications and one preprint about the LaNt proteins in the literature which means there is a massive potential to do novel, ground breaking research in this area.
In studies in our lab, we have shown that one member of the LaNt protein family regulates cell to matrix interaction in epithelial cells in a dish, is upregulated during times of stem cell activation and changes in expression and distribution during different stages of ex vivo wound repair. However, these studies were all completed in 2D and 3D culture environments and we’re now ready to move into more physiologically complete model systems. That’s where you will come in.
Recently, we have generated a transgenic mouse model to facilitate these studies. Your PhD studentship will involve using this model to study LaNt biology in the skin. We will cross our transgenic animals with other animals to generate skin specific overexpression. The double transgenics will provide a platform in which we can ask what effect increasing LaNt expression has on various aspects of cutaneous biology, both from a developmental point of view and during pathogenesis. Specifically, we will investigate the role of LaNt in the hair follicle stem cell activation, in cutaneous wound healing, in fibrosis and granulation tissue resolution and we will study skin cancer progression after induction of LaNt expression.
In completing this PhD you will receive extensive training in histological processing, genetic animal manipulations including surgery, creation of transgenic lines including cloning, processing of tissue for immunohistochemistry and immunofluorescence microscopy as well as transmission or scanning electron microscopy. There also will be opportunities to learn high end imaging techniques including light sheet, atomic force and super-resolution microscopy.
Part of my PhD studentship training ethos is that the student has opportunities to shape the direction of their project, and therefore we are more than willing to modify the experimental plans in ways that will be best suited for the student.
This project will add huge value to our understanding of the LaNt proteins and it will be an exciting project to be part of. We are therefore looking for someone with a passion for science who will become an active player in our highly collegiate research team. Experience in working with transgenic mice would be beneficial, however, training in all areas will be provided.
Informal enquiries are encouraged, feel free to get in touch.
Learn about the lab and our ongoing research here: www.lantsandlaminins.com
If you are interested in applying ofr this opportunity, then please contact Dr Kevin Hamill on [Email Address Removed]
There is NO funding attached to this project.
The successful applicant will be expected to provide the funding for tuition fees and living expenses as well as research costs of £9,000 per year.
Further details of current fees can be found on the University of Liverpool website.
Differential Distribution of Laminin N-Terminus α31 Across the Ocular Surface: Implications for Corneal Wound Repair. Invest Ophthalmol Vis Sci. 2018 Aug 1;59(10):4082-4093. Barrera V, Troughton L1, Iorio V, Liu S, Oyewole O, Sheridan CM, Hamill KJ. doi: 10.1167/iovs.18-24037 https://bit.ly/2ZHPl0U
[Preprint] LaNt α31 modulates LM332 organisation during matrix deposition leading to cell-matrix adhesion and migration defects. Valentina Iorio, Lee D. Troughton, Valentina Barrera, Kevin J. Hamill. doi: https://doi.org/10.1101/617597
Identification of a novel family of laminin N-terminal alternate splice isoforms: structural and functional characterization. Hamill KJ, Langbein L, Jones JC, McLean WH. J Biol Chem. 2009 Dec 18;284(51):35588-96. doi: 10.1074/jbc.M109.052811. https://bit.ly/2XRgFrW