Towards targeting altered glial biology in high-grade brain cancers

Towards targeting altered glial biology in high-grade brain cancers

Project details

In glioblastoma multiforme (GBM), depletion of the potassium channel Kir4.1 is a critical factor in adapting the shape of brain cancer cells to favour movement through tight spaces between cells in brain tissue. We are investigating a hypothesis that restoration of Kir4.1 activity to glial levels can be used to curtail cancerous invasion. To this end, we recently unravelled the complex mechanism underpinning activity in Kir channels, successfully predicting and achieving enhancement of activity.  

Student projects will be aimed at correlating Kir4.1 activity with invasiveness, relating it to changes in glioma cells, and working on a novel approach with potential to moderate GBM aggression.  

The primary location is in the Structural Biology division, but projects are collaborative with other labs at WEHI (imaging) and elsewhere (molecular dynamics; electrophysiology). 

About our research group

Our interests are in gaining an understanding of the complex allosteric mechanisms controlling potassium channels (with particularly relevance to this project) with a view to unlocking their therapeutic potential, to date an elusive goal for drug companies. We are also interested in mitochondrial translocases and have applied genetic methods to investigate association of translocase subunits with proteins from the apoptotic quality control in tissues undergoing Tom40-induced cell death. 

 We use structural (X-ray crystallography, Cryo-EM), biochemical, and biophysical methods to interrogate mechanism.  

Key collaborations for this project: 

Dr Verena Wimmer (WEHI Centre for Dynamic Imaging) 

Dr Hong Jian Zhu (Univ. Melbourne) 

Professor Derek Laver (Univ. Newcastle) 

Professor Brian Smith (LIMS) 

 

Email supervisors

 

Researchers:

Dr Jacqui Gulbis

Dr Jacqui Gulbis
Dr
Jacqui
Gulbis
Laboratory Head

Project Type: