The molecular mechanisms underlying Kir4.1 activity in gliomas

The molecular mechanisms underlying Kir4.1 activity in gliomas

Project details

Kir potassium channels present in glia maintain the osmotic environment of the brain. Disorders associated with loss or gain of function include sensorineural conditions such as epilepsy, depression, multiple sclerosis, EAST(SESAME) syndrome, Huntington’s disease and the invasiveness of brain cancers.

The mechanisms controlling conduction in Kir channels are uncertain. We are investigating allosteric processes controlling permeation in Kir channels, to identify features distinguishing the glial cell marker, Kir4.1. An intimate understanding of the relationship between structure and function will provide the means for rational, highly selective, pharmacological design targeting brain diseases.

The work entails membrane protein expression and biochemistry, constructing point mutations, employing cysteine-reactive probes for functional evaluation and testing channel function in bilayers, with potential for structural work. Training will be provided.

About our research group

Our group has a particular interest in establishing the allosteric mechanisms controlling potassium channels in the brain, and in activation and investigating the role of anionic lipids in regulation of potassium channel activity. We are also interested in mitochondrial translocases and have applied genetic methods to investigate association of translocase subunits with proteins from the apoptotic and necrotic pathways in tissues undergoing cell death. We utilize structural (X-ray crystallography, Cryo-EM), biochemical and biophysical methods to interrogate mechanism.

Researchers:

Dr Jacqui Gulbis

Dr Jacqui Gulbis
Dr
Jacqui
Gulbis
Laboratory Head

Project Type: