Northcott Neuroscience Laboratory
Lab head: Dr Marina Kenenrson
Location: ANZAC Research Institue
Unravelling the Molecular Basis of Motor and Sensory Neuron Degeneration
Primary supervisor: Marina Kennerson
In recent years significant progress has been made in finding the molecular causes of the premature death of neurons (neurodegeneration). The mechanisms of neurodegeneration can be divided into those that result in death of cell bodies (neuronopathies) and those that result in the ‘dying back’ of the distal neuron (axonal degenerations). Neurons are our longest (up to 1m) and most polarised cells. The unique morphology and the specialised cellular and energy requirements, highlight the inherent vulnerability of neurons to length dependent degeneration.
The Northcott Neuroscience Laboratory at the ANZAC Research Institute has an international reputation for mapping genes for Charcot-Marie-Tooth (CMT) disease, the most common and incurable group of disorders of the peripheral nervous system. Clinical characteristics of CMT include progressive distal limb weakness, muscle atrophy, loss of deep tendon reflexes, and sensory abnormalities. By discovering genes causing CMT we are defining proteins involved with the ‘dying back’ (axonal degeneration) of peripheral nerves. This pathogenic process is common to many neurodegenerative disorders including Parkinson’s disease, Alzheimer’s disease and motor neuron disease.
Gene discovery for CMT has entered an exciting era with the availability of next generation sequencing (NGS) technologies to expedite the gene mutation identification process. This project will contribute to ongoing work in our laboratory to identify gene mutations in families in which the underlying cause of CMT is unknown. Our current strategy is to sequence all known genes by using whole exome sequencing (WES). Students will be trained in molecular genetics and bioinformatics skills and gain practical experience in methods representing the latest advancements in human disease gene identification and gene functional studies. Specific techniques will include linkage analysis, high resolution melt (HRM) genotyping/mutation screening, bioinformatic analysis of exome sequence data, and molecular biology/cloning for validation and functional analysis of potential pathogenic DNA variants. These skills will be invaluable for students considering future postgraduate studies or pursuing a career in human neurogenetics/neurosciences.
The Northcott Neuroscience Laboratory is well resourced and currently holds two NHMRC grants and USA Muscular Dystrophy Association funding. The student will join a dynamic team of post doctoral fellows, research assistants and fellow students. This project highlights the integration of clinical practice and basic science to address an important aspect of neurogenetic research.
Co-supervisors: Alexander Drew, Gonzalo Perez-Siles
Keywords: Bioinformatics, Neuropathy, molecular genetics