Mapping genes for nerve disease

Summary

Our laboratory has an exemplary track record for mapping genes for inherited peripheral neuropathies. Charcot-Marie-Tooth (CMT) neuropathy is a degenerative disorder of the peripheral nerve affecting both the sensory and motor neurons. It is the most common disorder presenting in neurogenetic clinics with one in 2500 people affected. Neurons are the longest cells in the body and degeneration at their ends (axonal degeneration) is a common feature in many neurodegenerative disorders. Distal peripheral neuropathies exemplify this problem. Because of the chronic nature of these disorders the hereditary neuropathies are a poorly recognised and silent health burden with a lifetime cost to Australian measured in billions of dollars.  Mapping genes for peripheral neuropathies provides an opportunity to understand of the mechanisms involved in axonal degeneration and important molecules required for peripheral nerve development and function.

Supervisor(s)

Associate Professor Marina Kennerson, Professor Garth Nicholson

Research Location

Concord - ANZAC Research Institute

Program Type

Masters/PHD

Synopsis

Discovering Genes for Charcot Marie Tooth Neuropathy using Next Generation Sequencing  A project is available to discover genes causing dominant Charcot-Marie-Tooth neuropathy. Charcot-Marie-Tooth (CMT) neuropathy is a group of degenerative disorders of the peripheral nerve affecting both motor and sensory neurons. This clinically and genetically heterogeneous syndrome is the most commonly inherited neuromuscular disorder affecting 1 in 2,500 of people. The CMT phenotype is characterised with distal muscle wasting and weakness and pes cavus or foot drop. Sensory symptoms are not always present but may include numbness, pins and needles, loss of balance, and insensitivity to temperature and pain. In rare subtypes the disease is progressive and fatal. This project will focus on gene discovery for autosomal dominant forms of the disease (CMT1 and CMT2). Although there have been significant advances, there are still approximately 10% of CMT1 and 70% of CMT2 genes to be identified.  The advancement in sequencing technologies is providing affordable tools to identify gene mutations in families too small for traditional positional cloning approaches and heralds an exciting future for gene discovery in CMT research.

Additional Information

PhD candidates undertaking this project will have the opportunity to discover new genes causing this disorder. Techniques will encompass the use of bioinformatics tools to query databases and perform variant filtering for NGS data, standard molecular biology techniques for gene variant validation including high resolution melt analysis (HRM) and TaqMan assays for genotyping and gene expression analysis. In the latter stages of the candidature techniques to assess variants for pathogenicity will include cloning expression constructs, transfections, immunostaining, confocal microscopy with the possibility to study the gene variant in zebra fish models.   The PhD candidate will be encouraged to attend national and international conferences to present their work and will be exposed to an active and productive research environment that has current NHMRC funding. The strengths of this project are the unique clinical resources, utilising cutting edge genome technology for gene discovery and performing validation studies in an appropriate timeframe for a PhD candidature. The project will provide the student with extremely productive outcomes.

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Keywords

Bioinformatics, next generation sequencing, whole exome sequencing

Opportunity ID

The opportunity ID for this research opportunity is: 792

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