ProfessorMarina Kennerson

Summary of opportunity

Hereditary neuropathies still leave too many families without answers—but the next breakthroughs are hiding in the non-coding “dark genome.” Projects offered will use integrated WGS and RNA, long-read, and transcriptome-led discovery to uncover the missing genetic causes of unsolved axonal HN and fast-track new mechanisms toward precision therapies.

Opportunity Synopsis

Hereditary Neuropathies (HN) are a genetically heterogeneous group of disorders caused by the progressive degeneration of peripheral nerves. Onset typically leads to lifelong disability, characterized by muscle weakness, numbness, and chronic pain, all of which significantly impair daily function and quality of life for patients. There is currently no cure, and the development of effective therapies remains a critical unmet need. Our research program to study HN genetics is shifting beyond panels and exomes to investigate the non-coding “dark genome” with integrated WGS, long-read, repeat-expansion, and transcriptome-led approaches. This is uncovering previously hidden causes including complex SVs, repeats, regulatory and isoform disruption, particularly in unsolved axonal HN, creating exciting higher degree opportunities to close the diagnostic gap and translate new mechanisms into precision therapies.

Currently Supervising: PhD (2 Primary); Hons (1 Primary); International Internship ( 1 Primary)

Completed: PhD (4 Primary, 3 Auxiliary); MPhil (4 Primary, 3 Auxiliary); MSc Med (3 Auxiliary); Hons (7 Primary, 2 Auxiliary); PhD external (3 Auxiliary); MSc external (1 Auxiliary); International Internship ( 9 Primary).

Project Opportunities

Title: Mapping genes for nerve disease

Summary of opportunity:

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.

Opportunity 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.


Current Projects: