The mitochondrial TOM complex in neurodegenerative disease

The mitochondrial TOM complex in neurodegenerative disease

Project details

Age-related neurodegenerative diseases  such as Alzheimer’s and other dementias are associated with mitochondrial dysfunction leading to cell death. The TOM translocase essential for mitochondrial biogenesis has been linked to neurodegenerative diseases. We recently found that overexpression of Tom40 in a genetic model invokes regulated cell death pathways. In tissues undergoing cell death, some proteins from apoptotic and necrotic pathways integrate with Tom40 into large assemblies. We are employing structural, imaging and genetics methods to determine the changes to TOM assembly and biology that are invoked in stressed or dying cells.

A student would establish protocols for crosslinking of protein complexes embedded in isolated membranes and solubilising the crosslinked assemblies in preparation for a tandem crosslinking-proteomics approach, with potential for structure determination of complexes.

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 utilise 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: