ESR 9: Incorporation of hair follicle proto-follicles in skin constructs and study of their influence on skin structure and behaviour – United Kingdom

Host institution: Durham University (DU), United Kingdom


Supervisors:

  • Main supervisor: Dr. Colin Jahoda (DU, Department of Biosciences)

Enrolment PhD training program: DU


Planned secondments:

Brief description:

Our research has shown that 3D spheroidal microstructures created from human hair follicle dermal cells are capable of inducing new hair follicles in human skin. This ESR will work to enhance the inductive powers of follicle dermal cells and combine them with epithelial cells to create proto-follicles for skin constructs.


The project is divided into three specific objectives:

  • Creation of human proto-follicle structures with improved inductivity. Strategies will include the manipulation of hair follicle dermal cells by addition of secreted factors/small molecules, and gene manipulation with potential master regulator genes. Cells will be grown as 3D spheroids and analysed for upregulation of molecular markers of induction by qPCR, immunohistochemistry and sequencing. Dermal cells displaying enhanced follicle-inducing indicators will be combined with skin keratinocyte and follicle outer root sheath progenitor cells to create double-layered proto-follicles.
  • Incorporation of proto-follicles into skin constructs. Proto-follicles will be incorporated into skin constructs from partner groups. The optimum combination of scaffolds, cells and proto-follicles will be established in vitro by advanced imaging, and immunohistochemical analysis of key skin and hair follicle cellular components. We will also investigate the optimum organisation of proto-follicle spacing and depth within the constructs.
  • In vivo analysis of composite skin constructs. Constructs incorporating proto-follicles will be grafted onto immunodeficient rodent models and evaluated for the creation of functional hair follicles, and their influence on the cellular and extracellular environment. Our hypothesis is that follicle morphogenesis is accompanied by a cascade of associated developmental activities, including promotion of vascularisation, nerve supply and adipose tissue.

Project specific requirements:

  • MSc in Life Science/Biomedical sciences/Biology or similar
  • Practical experience in at least some of the following areas is highly recommended: culture of primary cells, cell transfection, basic molecular biology techniques, gene editing methods such as CRISPR/Cas9, immunohistochemistry, imaging/confocal microscopy
  • Knowledge of skin biology and familiarity with animal work would be helpful
  • Note that ESR project 9  requires additional application for a Postgraduate Course at Durham University: https://www.dur.ac.uk/study/pg/apply/

Please apply before December 21, 2020 via this APPLY link.