Investigation of Mechanisms Underpinning Keratinocyte Re-Epithelialisation During Wound Healing Using 3D Human Skin Equivalent Models

Overview

Topic status: We're looking for students to study this topic.

The mechanisms underlying wound reepithelialisation have been disputed protractedly, but remain ambiguous. To date the two main theories for how keratinocytes migrate across the wound bed are: 1. "Leap-Frogging": Keratinocytes located on the surface of the stratum basale at the wound edges creep into the wound bed. The cells above and following will crawl over the first cells and "lounge" on the wound bed in front of them; and 2. "Tractor tread": After the keratinocytes synthesize integrin receptors on their cell surface, they can migrate by using these integrin receptors to bind fibronectin,
vitronectin (VN) and other ECM proteins of the provisional wound bed. The partial-thickness de-epidermised dermis human skin equivalent (DED-HSE) 3D wound model developed in our laboratory has shown consistent wound reepithelialisation responses that are similar to those observed in human skin. Therefore, this project aims to study in vitro the mechanisms of wound reepithelialisation in a controlled partial-thickness DEDHSE 3D wound model. In particular this project will examine:

  • Aim 1: Detection of "Leap-Frogging" and "Tractor tread" during the reepithelialisation of the wound
  • Aim 2: Basement membrane components, integrin expression and protease activation during reepithelialisation of the wound
  • Aim 3: Signalling pathways involved in process of reepithelialisation, in particular those related to adhesion, migration and differentiation during wound healing

Methods and techniques that will be developed in the course of this project:

  • Construction of partial-thickness DED-HSE wound models
  • 2-D photon imaging and Histology and Immunohistochemistry
  • Transmission electron microscopy and Immunofluorescent microscopy
  • Western blot analysis and real-time PCR and Microarray analysis
Study level
PhD, Honours
Supervisors
QUT
Organisational unit

Science and Engineering Faculty

Research area

Cell and Molecular Biosciences

Contact
Please contact the supervisor.