Neurotrophic Laboratory

Neurotrophic Laboratory 2011
From left to right: Emeritus Prof Robert Rush, Dr Mary-Louise Rogers, Kevin Smith, Stephanie Shepheard.

For their growth and survival, neurons require unique proteins called neurotrophic factors, which are produced and secreted by cells within their immediate environment. The first of these to be discovered was Nerve Growth Factor (NGF), and this molecule now has been shown to be essential for the survival of sympathetic and some sensory neurons, as well as being a central regulator of cellular metabolism, not only within neurons, but for many other cell types. Scores of additional growth factors have been discovered in the past 30 years affecting different nerve classes and different aspects of nerve function.
Our laboratory has a particular focus on members of the NGF family, including Brain Derived Neurotrophic Factor (BDNF) and Neurotrophin 3 (NT3) and 4 (NT4) as well as on several other factors such as members of the GDNF family (Glial Derived Neurotrophic Factor). More recently, we have also investigated the role of the pro-Neurotrophins, particularly proBDNF and proNGF. The aim of much of our current research is to examine ways to use growth factors to prevent nerve degeneration due to disease or injury and to aid nerve regeneration. An ability to slow or prevent nerve degeneration and to facilitate nerve regeneration is important in conditions such as spinal cord injury, Motor Neuron Disease (also known as Amyotrophic Lateral Sclerosis - ALS) or following injury to individual nerves. A major focus of our research over the past year has been the study of Motor Neuron Disease and in particular finding new treatments for this devastating condition. Highlights for 2010 include the identification of a marker in a mouse model of the familial form of the disease which should allow earlier diagnosis and assist with testing of potential new treatments, as well as the discovery of a possible new drug which is showing promise in an animal model.

Investigators

Robert Rush, PhD, Emeritus Professor
Mary-Louise Rogers, PhD, Lecturer

Support Staff

Sortiria Bexis, PhD, Research Assistant

Students

Stephanie Shepheard, BMSc(Hons), PhD student
Kevin Smith, BSc(Hons), PhD student

Contacts

Dr Mary-Louise Rogers		E. Prof Robert Rush
Ph: (08) 8204 5320 Int Ph: +61 8 8204 5320 Fax: (08) 8204 5768 Int Fax: +61 8 8204 5768 Email: mary-louise.rogers@flinders.edu.au University Profile Page		Ph: (08) 8204 5238 Int Ph: +61 8 8204 5238 Fax: (08) 8204 5768 Int Fax: +61 8 8204 5768 Email: robert.rush@flinders.edu.au University Profile Page

Research Projects

• Targeting genes into diseased motor neurons
  • Demonstration of Specific, Non-Viral Gene Delivery Targeting Motor Neurons in-vitro and in-vivo through the p75NTR receptor
  • Quantification of the transfection efficiency and toxicity of p75NTR non-viral gene delivery in wild type and SOD1G93A primary motor neuron cultures
  • Development of an immunogene targeting adult motor neurons
  • A biomarker for Motor Neuron Disease

Collaborative Research

Prof Kenneth Neet, Rosalind Franklin University of Medicine and Science, Chicago: Biological activity of a mutant form of proNGF in NK cells.

Prof Doug Brooks and Dr Revecca Kakavanos, Samson Institute, University of South Australia: Targeted gene delivery for the treatment of Liposomal Storage Disease.

Prof Neil Sims and Dr Håkan Muyderman, Medical Biochemistry, Flinders University: Targeted gene transfer into glial cells.

Prof Uri Saragovi (McGill University, Canada) and Prof Neil Cashman ( University of British Columbia): Function of TrkC in spinal motor neurons.

Assoc Prof Simon Koblar, University of Adelaide: Role of p75NTR in dental pulp stem cells.

Selected Recent Publications

Rogers M-L, Bailey S, Matusica D, Nicholson I, Muyderman H, Pagadala PC, Neet KE, Zola H, Macardle P and Rush RA (2010) ProNGF mediates death of Natural Killer cells through activation of the p75NTR-Sortlin complex. J of NeuroImmunology, 226(1-2):93-103

Wiese S, Herrmann T, Drepper C, Jablonka S, Funk N, Klausmeyer A, Rogers M-L, Rush R, Sendtner M (2010) Isolation and enrichment of embryonic mouse motoneurons from the lumbar spinal cord of individual mouse embryos. Nat Protoc, 5:31-38

Muyderman H, Hutson PG, Matusica D, Rogers ML, Rush RA (2009) The Human G93A-Superoxide Dismutase-1 Mutation, Mitochondrial Glutathione and Apoptotic Cell Death. Neurochem Res. 34(10):1847-56

Rogers ML, Beare A, Zola H and Rush RA (2008) CD271, p75 Neurotrophin Receptor. J Biol Reg, 22(1): 1-6

Matusica D, Fenech MP, Rogers ML, Rush RA (2008) Characterization and use of the NSC-34 cell line for study of neurotrophin receptor trafficking. J Neurosci Res, 15:553-565

Feng SQ, Zhou X-F, Rush RA and Ferguson IA (2008) Graft of pre-injured sural nerve promotes regeneration of corticospinal tract and functional recovery in rats with chronic spinal cord injury. Brain Research, 1209:40-48

Berhanu DA and Rush RA (2008) Targeted silencing of TrkA expression in rat forebrain neurons via the p75 receptor. Neuroscience, 153(4): 1115-1125

 

Updated July 3, 2011