Keast-Osborne Laboratory: Neural and Bioelectronic Control of Pelvic Organs
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Professor Janet Keast & A/Professor Peregrine Osbornejkeast@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 reveal how the nerve circuit functions and to use this knowledge to 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 supported by the US National Institutes of Health (NIH) as foreign principal investigators in two research consortia:
- GenitoUrinary Development Molecular Anatomy Project (GUDMAP)
This 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 genitourinary tract. - Stimulating Peripheral Activity to Alleviate Conditions (SPARC) Common Fund Program
This initiative of the NIH Office of the Director aims to accelerate development of bioelectronic medicine.
We are also members of 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
Postdoctoral Research Fellows
- Maria Daglas PhD, Microscopy and Neuroanatomy
- John-Paul Fuller-Jackson PhD, Microscopy and Neuroanatomy
- Alicia Yang PhD, Computational Image Analysis
Research Support Officers
- Luke Bowden
- Dain Maxwell, Laboratory Manager
Graduate Researchers
- Lorenzo Bosio, PhD Student Melbourne-CNRS Network
- Aymeric Nadjem, PhD Student Melbourne-CNRS Network
- Kayleigh Scotcher, PhD Student
Collaborators
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
Prof Viviana Gradinaru, Caltech
Prof Peter Hunter, University of Auckland
Dr Sophie Payne, Bionics Institute and University of Melbourne
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
University of Melbourne – Centre National de la Recherche Scientifique (CNRS) Network: 2022-2025. Solving the puzzle of the human pelvic plexus: a developmental and multiscale imaging approach
US National Institutes of Health - National Institute of Diabetes Digestive and Kidney Disease (NIDDK) 2021-2026. GenitoUrinary Development Molecular Anatomy Project (GUDMAP): Building a multi-scale vascular atlas of the mouse lower urinary tract
US National Institutes of Health 2016-2024 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 Publications
- Wiedmann NM, Fuller-Jackson JP, Osborne PB, Keast JR. An adeno-associated viral labelling approach to visualise the meso- and microanatomy of mechanosensory afferents and autonomic innervation of the rat urinary bladder. FASEB J. Accepted Dec 5, 2023.
- Payne SC, Osborne PB, Thompson A, Eiber CD, Keast JR, Fallon JB. Selective recording of physiologically evoked neural activity in a mixed autonomic nerve using a minimally invasive array. APL Bioeng. 2023 Dec;7(4):046110. doi: 10.1063/5.0164951. eCollection 2023 Dec. PubMed PMID: 37928642; PubMed Central PMCID: PMC10625482.
- Liu JY, Grayden DB, Keast JR, John SE. Computational modeling of endovascular peripheral nerve stimulation using a stent-mounted electrode array. J Neural Eng. 2023 May 15;20(3). doi: 10.1088/1741-2552/aca69e. PubMed PMID: 36595262.
- 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
- Fuller-Jackson JP, Osborne PB, Keast JR. Regional Targeting of Bladder and Urethra Afferents in the Lumbosacral Spinal Cord of Male and Female Rats: A Multiscale Analysis. eNeuro. 2021 Nov-Dec;8(6). doi: 10.1523/ENEURO.0364-21.2021. Print 2021 Nov-Dec. PubMed PMID: 34772694; PubMed Central PMCID: PMC8690816.
- 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.
- 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.
- 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.
- 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.
- Keast JR, Osborne PB. Autonomic Nervous System and Male Reproduction. In: Skinner MK, Jegou B, editors. Encyclopedia of Reproduction Second ed. Amsterdam: Elsevier; 2018.
Recent highlights
Research Projects
- Building a urogenital nervous system connectome
- Development of autonomic and nociceptive circuits
- Neuroanatomy of human visceral systems
- Functional neuroanatomy of genitourinary vasculature
Faculty Research Themes
School Research Themes
Cardio-Respiratory, Biomedical Neuroscience, Cellular Imaging & Structural Biology, Systems Biology, Molecular Mechanisms of Disease
Key Contact
For further information about this research, please contact Joint Heads of Laboratory Professor Janet Keast & A/Professor Peregrine Osborne
Department / Centre
Unit / Centre
Keast-Osborne Laboratory: Neural and Bioelectronic Control of Pelvic Organs
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