Keast-Osborne Laboratory: Neural and Bioelectronic Control of Pelvic Organs

• 
  Joint Heads of Laboratory
  Professor Janet Keast & Dr Peregrine Osborne

  jkeast@unimelb.edu.au peregrine.osborne@unimelb.edu.au

  +61 3 8344 5805 +61 3 9035 9716

Research Overview

^{View our Publications (Keast | Osborne) and Find an Expert profiles (Keast | Osborne)}

Voiding, reproduction and other human pelvic functions require complex neural control to occur normally at behaviourally appropriate times. Our goal is to help develop neuromodulation and other therapies to treat related human clinical conditions, many of which severely compromise quality of life over long periods.

Our work is  funded  by the US National Institutes of Health (NIH) as foreign principal investigators in two research consortia

• GenitoUrinary Development Molecular Anatomy Project (GUDMAP), which is a program funded by the US National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK) to provide a fundamental description of the developing kidney and GU tract.

We are also funded by the Melbourne-CNRS network in partnership with the Chédotal laboratory (Sorbonne Université/INSERM/CNRS, France).

Our research focuses on the pelvic nervous system and how this neural interface is used by the brain to exert control over the pelvic organs and genitalia. We use advanced neuroanatomical, microscopy, image analysis and digital mapping techniques to study the neural control control circuit and target organs—but we are also expert in other approaches including primary cell culture, neurophysiology and neuropharmacology.

Our research is determining

• how the pelvic nervous system and vasculature develops
• how neural circuits control complex bodily functions such as voiding or reproduction
• how can neuromodulation be used as 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 (focusing on  human inferior hypogastric plexus and rodent major pelvic ganglia)
• pelvic somatosensory and visceral sensory systems
• sacral and lumbar spinal cord
• and connectivity with high order brain centres.

^{Strategies for therapeutic neuromodulation of urinary disorders
https://doi.org/10.1152/ajprenal.00372.2017}

Staff

Adam Blanch PhD, Postdoctoral Research Fellow, Microscopy and Anatomy

Alicia Yang PhD, Postdoctoral Research Fellow, Neuroinformatics and Computational Bioengineering

Anita Peura  PhD, Research  Support Officer

Dain Maxwell, Research  Support Officer

Ilvana Ziko PhD, Research Support Officer, Laboratory Manager

John-Paul Fuller-Jackson PhD, Postdoctoral Research Fellow, Microscopy and Neuroanatomy

Jonathon Chan PhD, Postdoctoral Research Fellow, Microscopy and Neuroanatomy

Maria Daglas PhD, Postdoctoral Research Fellow, Microscopy and Neuroanatomy

Nicole Wiedmann PhD, Postdoctoral Research Fellow, Microscopy and Neuroanatomy

Students 

Luke Bowden, BBiomedSci Honours Student

Lakindu Jayasuriya, BBiomedSci Honours Student

Collaborators

Assoc Prof Martin Bertrand, University of Nimes, France

Prof  Alain  Chédotal, Sorbonne Université Institut de la Vision, CNRS UMR 7210

Prof James Fallon, Bionics Institute and University of Melbourne

Assoc Prof Jane Girling, University of Otago, New Zealand

Prof Viviana Gradinaru, Caltech

Prof Leif Havton, Icahn School of Medicine and UCLA

Prof Peter Hunter, University of Auckland

Assoc Prof Joseph Ischia, Austin Health and University of Melbourne

Dr Sophie Payne, Bionics Institute and University of  Melbourne

Prof Michelle Southard-Smith, Cell and Developmental Biology, Vanderbilt University

Dr Doug Strand, University of Texas Southwestern

Dr Alan Watson, University of Pittsburgh

Prof Chad Vezina, University of Wiscosin - Madison

University of Melbourne

Prof David Grayden, Department of Biomedical Engineering

Dr Sam John, Department of Biomedical Engineering

Professor  Scott Mueller, Department of Microbiology and Immunology

Funding

US National Institutes of Health 2021-2026
National Institute of Diabetes Digestive and Kidney Disease (NIDDK); GenitoUrinary Development Molecular Anatomy Project (GUDMAP): Building a multi-scale vascular atlas of the mouse lower urinary tract

US National Institutes of Health 2016-2022
Stimulating Peripheral Activity to Relieve Conditions (SPARC) Common Fund Program: 'Foundational Functional Mapping of Neuroanatomy and Neurobiology of Organs'

NCRIS (National Collaborative Research Infrastructure Strategy) 2014-2021
Phenomics Australia: Phenomics Australia Histopathology and Digital Slide Service

US National Institutes of Health 2013-2015
National Institute of Diabetes, Digestive and Kidney Disease (NIDDK); Nociceptive GenitoUrinary Development Molecular Anatomy Project (nGUDMAP): Molecular and spatial mapping of bladder nociceptors during development and maturation'

US National Institutes of Health 2011-2016
National Institute of Diabetes, Digestive and Kidney Disease (NIDDK); GenitoUrinary Development Molecular Anatomy Project (GUDMAP): 'High resolution mapping of lower urinary tract innervation during development'

Research Opportunities

This research project is available to PhD students, Masters by Research, Honours students, Master of Biomedical Science to join as part of their thesis.
Please contact the Research Group Leader to discuss your options.

Research Publications

Recent highlights

• Chen X, Kumar SV, Adams CD, Yang D, Wang T, Wolfe DA，Arokiaraj CM, Ngo Victoria, Campos LJ, Griffiths JA, Ichiki T, Mazmanian SK, Osborne PB, Keast JR, Miller CT, Fox AS, Chiu IM, Gradinaru V (2022) Engineered AAVs for non-invasive functional transgene expression in rodent and non-human primate central and peripheral nervous systems. Neuron. 2022 Jul 20;110(14):2242-2257.e6. doi: 10.1016/j.neuron.2022.05.003. PMID: 35643078.
• Loi JK, Alexandre YO, Senthil K, Schienstock D, Sandford S, Devi S, Christo SN, Mackay LK, Chinnery HR, Osborne PB, Downie LE, Sloan EJ, Mueller SN (2022) Corneal tissue resident memory T cells form a unique immune compartment at the ocular surface. Cell Rep. 2022 May 24;39(8):110852. doi: 10.1016/j.celrep.2022.110852. Pubmed PMID: 35613584.
• Plebani E, Biscola N, Havton L, Rajwa B, Shemonti A, Jaffey D, Powley T, Keast JR, Lu K-H, Dundar M. (2022) High-throughput segmentation of unmyelinated axons by deep learning.  Sci Rep 12: 1198 (2022). doi.org/10.1038/s41598-022-04854-3 PubMed PMID: 35075171
• Liu JY, Grayden DB, Keast JR, John S. Computational modeling of an endovascular peripheral nerve interface. Annu Int Conf IEEE Eng Med Biol Soc 2021 Nov;2021:5966-5969 doi:  10.1109/EMBC46164.2021.9630085 PubMed PMID: 34892477
• Eiber C, Payne SC, Biscola N, Havton L, Keast JR, Osborne PB, Fallon JB Computational modelling of nerve stimulation and recording with peripheral visceral neural interfaces. J Neural Eng. 2021  doi: 10.1088/1741-2552/ac36e2.  PubMed PMID: 34740201.
• Colgrave EM, Keast JR, Bittinger S, Healey M, Rogers PAW, Holdsworth-Carson SJ, Girling JE. Comparing endometriotic lesions with eutopic endometrium: time to shift focus?. Hum Reprod. 2021 Oct 18;36(11):2814-2823. doi: 10.1093/humrep/deab208. PubMed PMID: 34535995.
• Yang CC, Hokanson JA, Keast JR. Advancing our understanding of the neural control of the female human urethra. Neurourol Urodyn. 2021 Oct 4;. doi: 10.1002/nau.24807. PubMed PMID: 34605569.
• Colgrave EM, Bittinger S, Healey M, Dior UP, Rogers PAW, Keast JR, Girling JE, Holdsworth-Carson SJ. Reply: The heterogeneity of endometriotic lesions could be explained by their progesterone resistance. Hum Reprod. 2021 Aug 18;36(9):2625-2626. doi: 10.1093/humrep/deab150. PubMed PMID: 34160602.
• Smith-Anttila CJA, Morrison V, Keast JR. Spatiotemporal mapping of sensory and motor innervation of the embryonic and postnatal mouse urinary bladder. Dev Biol. 2021 Aug;476:18-32. doi: 10.1016/j.ydbio.2021.03.008. Epub 2021 Mar 17. PubMed PMID: 33744254.
• Turco AE, Oakes SR, Keil Stietz KP, Dunham CL, Joseph DB, Chathurvedula TS, Girardi NM, Schneider AJ, Gawdzik J, Sheftel CM, Wang P, Wang Z, Bjorling DE, Ricke WA, Tang W, Hernandez LL, Keast JR, Bonev AD, Grimes MD, Strand DW, Tykocki NR, Tanguay RL, Peterson RE, Vezina CM. A mechanism linking perinatal 2,3,7,8 tetrachlorodibenzo-p-dioxin exposure to lower urinary tract dysfunction in adulthood. Dis Model Mech. 2021 Jul 1;14(7). doi: 10.1242/dmm.049068. Epub 2021 Jul 27. PubMed PMID: 34318329; PubMed Central PMCID: PMC8326766.
• Wiedmann NM, Wong AW, Keast JR, Osborne PB. Sex differences in c-Fos and EGR-1/Zif268 activity maps of rat sacral spinal cord following cystometry-induced micturition. J Comp Neurol. 2021 Feb;529(2):311-326. doi: 10.1002/cne.24949. Epub 2020 Jun 11. PubMed PMID: 32415681
• Payne SC, Wiedmann NM, Eiber CD, Wong AW, Senn P, Osborne PB, Keast JR, Fallon JB. Recording of Electrically Evoked Neural Activity and Bladder Pressure Responses in Awake Rats Chronically Implanted With a Pelvic Nerve Array. Front Neurosci. 2020;14:619275. doi: 10.3389/fnins.2020.619275. eCollection 2020. PubMed PMID: 33390899.
• Colgrave EM, Bittinger S, Healey M, Dior UP, Rogers PAW, Keast JR, Girling JE, Holdsworth-Carson SJ. Superficial peritoneal endometriotic lesions are histologically diverse and rarely demonstrate menstrual cycle synchronicity with matched eutopic endometrium. Hum Reprod. 2020 Dec 1;35(12):2701-2714. doi: 10.1093/humrep/deaa249. PubMed PMID: 33300558.
• Bertrand MM, Korajkic N, Osborne PB, Keast JR. Functional segregation within the pelvic nerve of male rats: a meso- and microscopic analysis. J Anat. 2020 Oct;237(4):757-773. doi: 10.1111/joa.13221. Epub 2020 Jun 29. PubMed PMID: 32598494; PubMed Central PMCID: PMC7495281.
• Eiber CD, Keast JR, Osborne PB. Simulating bidirectional peripheral neural interfaces in EIDORS. Annu Int Conf IEEE Eng Med Biol Soc. 2020 Jul;2020:2934-2937. doi: 10.1109/EMBC44109.2020.9175921. PubMed PMID: 33018621.
• Bertrand MM, Keast JR. Dissection of Pelvic Autonomic Ganglia and Associated Nerves in Male and Female Rats. J Vis Exp. 2020 Mar 7;(157). doi: 10.3791/60904. PubMed PMID: 32202526.
• Smith-Anttila CJA, Mason EA, Wells CA, Aronow BJ, Osborne PB, Keast JR. Identification of a Sacral, Visceral Sensory Transcriptome in Embryonic and Adult Mice. eNeuro. 2020 Jan/Feb;7(1). doi: 10.1523/ENEURO.0397-19.2019. Print 2020 Jan/Feb. PubMed PMID: 31996391; PubMed Central PMCID: PMC7036621.
• Turco AE, Cadena MT, Zhang HL, Sandhu JK, Oakes SR, Chathurvedula T, Peterson RE, Keast JR, Vezina CM. A temporal and spatial map of axons in developing mouse prostate. Histochem Cell Biol. 2019 Jul;152(1):35-45. doi: 10.1007/s00418-019-01784-6. Epub 2019 Apr 11. PubMed PMID: 30976911; PubMed Central PMCID: PMC6685201.
• Wong AW, Osborne PB, Keast JR. Axonal Injury Induces ATF3 in Specific Populations of Sacral Preganglionic Neurons in Male Rats. Front Neurosci. 2018;12:766. doi: 10.3389/fnins.2018.00766. eCollection 2018. PubMed PMID: 30405344; PubMed Central PMCID: PMC6207596.
• Keast JR, Osborne PB. Autonomic Nervous System and Male Reproduction. In: Skinner MK, Jegou B, editors. Encyclopedia of Reproduction Second ed. Amsterdam: Elsevier; 2018.