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 a neural interface that is used by the brain to exert control over and coordinate the relevant visceral and somatic systems. This requires understanding an especially complicated area of the spinal cord - the sacral cord - that combines both somatic and visceral networks, and the pelvic ganglia that has an unusual mixture of both sympathetic and parasympathetic neurons. 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 research mostly uses rodent models to study the development, anatomy, and function of the 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 high order brain centres. We use advanced microscopic imaging and neuroanatomical techniques extensively in our work, but are also expert in using a variety of other approaches  that include 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 also participating in the GUDMAP project funded 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. This can be accessed via the online GenitoUrinary Development Molecular Anatomy Project database.

Staff

Dr Peregrine Osborne,  Co-Head of Laboratory, Senior Research Fellow
Dr Agnes Wong, Postdoctoral Research Fellow
Dr Casey Smith-Anttila, Postdoctoral Research Fellow
Elsbeth Richardson, Research Support Officer
Victoria Morrison, Research Support Officer
Dr Yanqiu Hu, Postdoctoral Research Fellow

Collaborators

Professor Bruce Aronow, Cincinnati Childrens
Professor Andy McMahon, Keck School of Medicine, University of Southern California
Professor Cathy Mendelsohn, Urology, Pathology & Cell Biology, Columbia University
Professor Erica Fletcher, Anatomy and Neuroscience, The University of Melbourne
Professor Mart Saarma, Institute of Biotechnology, University of Helsinki
Associate Professor Michelle Southard-Smith, Cell and Developmental Biology, Vanderbilt University
Associate Professor Sanjay Jain, Washington University Medical School, St Louis
Dr Jaan-Olle Andressoo, 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 Helen O'Connell, Royal Melbourne Hospital and University of Melbourne
Professor Rob Shepherd, Bionics Institute, Melbourne.

Funding

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

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'

Research Publications

  • 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.
  • 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.