Keast & Osborne laboratory: Neural development, injury and pain

  • Joint Heads of Laboratory

    Professor Janet Keast & Dr Peregrine Osborne
    T: +61 3 8344 5804, +61 3 9035 9716 (PO)
    E: jkeast@unimelb.edu.au
    Location: E725 & E720 (PO), Level 07, Medical Building, Parkville
    W: Personal web page

Research Overview

Voiding and reproduction are important human functions that require complex reflexes to occur at behaviourally appropriate times. The pelvic nervous system is the neural interface used by the brain to exert control over the relevant visceral and somatic systems.  

Our goal is help develop neuromodulation and other therapies to treat human clinical conditions affecting these functions.

To do this, our research is determining how the pelvic nervous system develops; how it controls complex bodily functions such as voiding or reproduction; and how it might be manipulated to provide clinical  treatments in diverse medical specialties including urology, gastroenterology, sexual medicine, neurology and pain medicine.

Our multidisciplinary approach uses rodent models and human samples to study the development, anatomy, and function of the pelvic nervous system, which comprises 

  • major subdivisions of the parasympathetic and sympathetic autonomic nervous system
  • pelvic somatosensory and visceral sensory systems
  • sacral and lumbar spinal cord
  • and connectivity with high order brain centres.  

We use advanced microscopic imaging and neuroanatomical techniques extensively in our work, but are also expert in other approaches such as primary cell culture (including co-cultures of adult neurons and urothelial cells), cellular neurophysiology and neuropharmacology, and  bioinformatics analysis of specific neural populations.

We are supported by the National Institutes of Health SPARC common fund program and have also contributed to the GenitoUrinary Development Molecular Anatomy Project database (GUDMAP) program funded by the US National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK), which aims to provide a fundamental description of the developing kidney and GU tract.

Staff

Dr Peregrine Osborne,  Co-Head of Laboratory, Senior Research Fellow
Dr Agnes Wong, Postdoctoral Research Fellow
Victoria Morrison, Research Support Officer
Nicole Hunter, Research Support Officer

Collaborators

Associate Professor Sanjay Jain, Washington University Medical School, St Louis
Associate Professor James Fallon, Bionics Institute, The University of Melbourne
Associate Professor Stuart Mazzone, Anatomy and Neuroscience, The University of Melbourne
Professor Cathy Mendelsohn, Urology, Pathology & Cell Biology, Columbia University
Professor Mart Saarma, Institute of Biotechnology, University of Helsinki
Dr Scott Mueller, Dept of Microbiology and Immunology, The University of Melbourne
Professor Steve Petrou, The Florey Institute of Neuroscience and Mental Health, The Unversity of Melbourne
Professor Rob Shepherd, Bionics Institute, Melbourne
Associate Professor Michelle Southard-Smith, Cell and Developmental Biology, Vanderbilt University
Professor Christine Wells, Anatomy and Neuroscience, The University of Melbourne.

Funding

National Institutes of Health; Stimulating Peripheral Activity to Relieve Conditions (SPARC) Common Fund Program 'Foundational Functional Mapping of Neuroanatomy and Neurobiology of Organs'

National Institutes of Health; National Institute of Diabetes, Digestive and Kidney Disease (NIDDK) 'Molecular and spatial mapping of bladder nociceptors during development and maturation'

National Institutes of Health; National Institute of Diabetes, Digestive and Kidney Disease (NIDDK) 'High resolution mapping of lower urinary tract innervaiton during development'

NCRIS (National Collaborative Research Infrastructure Strategy)

NHMRC Project Grant 'Strategies to restore bladder control after peripheral nerve injury'

NHMRC Project Grant 'Spinal cord injury pain: defining mechanisms to develop treatments

Research Publications

  • Sidorova YA, Bespalov MM, Wong AW, Kambur O, Jokinen V, Lilius TO, Suleymanova I, Karelson G, Rauhala PV, Karelson M, Osborne PB, Keast JR, Kalso EA, Saarma M. A novel small molecule GDNF receptor RET agonist, BT13, promotes neurite growth from sensory neurons in vitro and attenuates experimental neuropathy in the rat. Frontiers in Neuropharmacology. Accepted. 27 May 2017.
  • Keast JR, Smith-Anttila CJ, Osborne PB. Developing a functional urinary bladder: a neuronal context. Front Cell Dev Biol 2015; 3(53). doi: 10.3389/fcell.2015.0005.
  • Georgas KM, Armstrong J, Keast JR, Larkins CE, McHugh KM, Southard-Smith EM, Cohn MJ, Batourina E, Dan H, Schneider K, Buehler DP, Wiese CB, Brennan J, Davies JA, Harding SD, Baldock RA, Little MH, Vezina CM, Mendelsohn C. An illustrated anatomical ontology of the developing mouse lower urogenital tract. Development 2015 May 15;142(10): 1893-908. doi: 10.1242/dev.117903.
  • Forrest SL, Osborne PB, Keast JR. Characterization of axons expressing the artemin receptor in the female rat urinary bladder: a comparison with other major neuronal populations. J Comp Neurol 2014;522(17): 3900-27. doi: 10.1002/cne.23648.
  • Christie MJ, Osborne PB (2013) Opioid electrophysiology in PAG. In: Gebhart GF, Schmidt RF (Eds.) Encyclopedia of Pain 2nd Ed. Springer Heidelberg.
  • Densmore VS, Kalous A, Keast JR, Osborne PB. Above-level mechanical hyperalgesia in rats develops after incomplete spinal cord injury but not after cord transection, and is reversed by amitriptyline, morphine and gabapentin. Pain 2010;151(1): 184-93. doi:10.1016/j.pain.2010.07.007.
  • Keast JR, Forrest SL, Osborne PB. Sciatic nerve injury in adult rats causes distinct changes in the central projections of sensory neurons expressing different glial cell line-derived neurotrophic factor family receptors. J Comp Neurol 2010;518(15): 3024-45. doi: 10.1002/cne.22378.
  • Xu S, Cheng Y, Keast JR, Osborne PB. 17beta-estradiol activates estrogen receptor beta-signalling and inhibits transient receptor potential vanilloid receptor 1 activation by capsaicin in adult rat nociceptor neurons. Endocrinology 2008;149(11):5540-8. doi: 10.1210/en.2008-0278.
  • Yan H, Keast JR. Neurturin regulates postnatal differentiation of parasympathetic pelvic ganglion neurons, initial axonal projections, and maintenance of terminal fields in male urogenital organs. J Comp Neurol 2008; 507(2): 1169-83. doi: 10.1002/cne.21593.
  • Forrest SL, Keast JR. Expression of receptors for glial cell line-derived neurotrophic factor family ligands in sacral spinal cord reveals separate targets of pelvic afferent fibers. J Comp Neurol 2008 Feb 20;506(6): 989-1002.