Extracerebral brain metastases account for 90% of all brain malignancies, outnumbering primary brain cancers. Melanoma originates in collagen rich skin yet exhibits tropism to the brain which exhibits unique mechanical properties due to the brain ECM being heavily composed of glycosaminoglycans (GAGs) including hyaluronic acid (HA) and tenascin. Mechanical stiffness of the microenvironment plays key roles in cell survival, response to therapies and metastatic ability of cancer. The mechanical role of the brain microenvironment remains poorly explored for melanoma. As such, we are aiming to establish mechanically relevant three-dimensional cell culture models of MBM (melanoma brain metastases) from patient-derived cell lines. Investigate MBM motility, proliferation, and survival in brain mimetic matrices using a combination of high-resolution live-cell microscopy, cutting-edge bio-reporters, immunofluorescence and 3D cell culture. We aim to understand the contribution of the mechanical microenvironment and the bi-directional role of the cytoskeleton and cell-matrix adhesions.
Traineeships, honours and PhD projects include:
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The role of the mechano-environment in metastatic disease and therapy resistance
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Establish biochemically and biophysically relevant three-dimensional brain-mimetic cell culture models of MBM
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Understand the role glial cell reprograming and melanoma cell crosstalk (collaboration with Melanie White)
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Investigating MBM and the blood brain barrier (collaboration with Anne Lagendijk)
Who can apply to how to apply:
Students looking for research projects (Honours, Masters by research or PhD). A working knowledge of Cell Biology, Microscopy and microfluidics would be of benefit to someone working on this project. The applicant will demonstrate academic achievement in the field(s) of Cell Biology and the potential for scholastic success. A background or knowledge of Engineering/optics is highly desirable. Please contact Dr Samantha Stehbens
