Dr Kip Gabriel

Research Fellow

Mitochondrial Functional and Disease Biology

Tel:      +61-3-9902 9213

Fax:     +61-3-9905 3726

Office:  Room 253, Level 2, Building 76 (STRIP 2)

Email:   kip.gabriel@med.monash.edu.au

The Mitochondrial functional and disease biology laboratory is particularly interested in diseases or infections that cause or are caused by mitochondrial pathologies.

Link to Molecular Biology of Host-pathogens Interactions

Current Projects in the Laboratory

1.  Understanding the molecular pathologies leading to the onset and acceleration of Alzheimer's disease.  

Two significant pathologies during progression of Alzheimer's disease are mitochondrial dysfunction and the appearance of plaque regions in the brain. Apart from being sparse in live cellular material these plaque regions are rich in a peptides that form amyloid fibrils known as Amyloid beta peptides (Abeta). These peptides are proteolytic products of a larger protein called Amyloid Precursor protein. Amyloid Precursor Protein and Abeta have been reported to be targeted to mitochondria where they cause pathologies in addition to the plasma membrane.

Image taken from http://rst.gsfc.nasa.gov/Intro/Part2_26c.html

We are currently trying to understand the mechanism behind the measured mitochondrial pathologies, attempting to elucidate the trafficking pathways of Amyloid Precursor Protein and determine the factors that lead to it being targeted to mitochondria or cleaved into Abeta fragments during Alzheimer’s disease progression.

In collaboration with Dr. Andrew Hill at the University of Melbourne we utilise a variety of human and mouse derived cultured cell lines and mouse model systems to investigate these processes.

2.  Mutations in the Protein Kinase PINK1 cause PARK6 familial Parkinson’s disease.

PINK1 is a Protein Kinase that was recently discovered to be targeted to mitochondria and the cytosol. We are elucidating how and why PINK1 is targeted to mitochondria, which compartment it resides in and determining which proteins are its substrates. This work is a close collaboration with Associate Professor Heung-Chin Cheng (Biochemistry & Molecular Biology) and Dr. Janetta Culvenor (Pathology) at the University of Melbourne.

3.  The protein PorB from the meningitis causing bacterium Neisseria meningitidis affects human cells during invasion of the nervous system.

In collaboration with ARC Federation Fellow Professor Trevor Lithgow and Professor John Davies (Microbiology) we are currently investigating how the Neisserial beta barrel protein PorB, is targeted and assembled in mitochondria and the functional effects it has on human mitochondria. Of particular interest is coming to an understanding of how these mitochondrial events play out in the pathology of meningococcal disease.

4.  Stomach ulcers are caused by the bacterium Helicobacter pylori.

A protein from this bacterium, VacA, is targeted to mitochondria. Exactly how VacA assembly contributes to pathogenesis of Helicobacter infection remains of interest. In collaboration with Dr. Terry Kwok-Schuelein and Dr. Richard Ferrero (Microbiology) we are examining how this protein is assembled in mitochondria.

Honours and PhD Projects on these topics are currently available in the laboratory. The lab uses a wide range of Cell and Molecular Biology techniques to study protein trafficking and mitochondrial biology.

Commonly Used Techniques

• Confocal microscopy
• Cell fractionation
• SDS and Blue native electrophoresis
• Mammalian tissue culturing
• Yeast genetics
• Protein expression
• In vitro protein translocation assays

Last updated on 9 February 2009