There are three main types of pain: nociceptive pain, the type we’re most familiar with, from bee stings and ankle strains to inflammatory arthritis. There’s neuropathic pain, arising from damage to the peripheral nervous system or the brain itself due to disease or injury. Then there are functional pain disorders arising from complex organic dysfunction, sometimes called ‘primary pain’, but most often just known as ‘other’. Continue reading
Pain is a normal part of life, but persistent pain is oppressive to endure. “It is easier to find men who will volunteer to die,” said Roman emperor Julius Caesar, “than to find those who are willing to endure pain with patience.” Continue reading
21 November 2019: By Kathy Nicholson
Recently, Dr Sanam Mustafa and I nominated our colleague Professor Mark Hutchinson for a VC Award for Outstanding Achievements.
Today we found out our nomination was successful. Continue reading
CNBP has officially welcomed UNSW, one of the world’s leaders at translational engineering research, as its newest node.
In addition to the official open by UNSW Engineering Dean Professor Mark Hoffman, CNPB Director Professor Mark Hutchinson took the opportunity to lay out the CNBP mission and its accomplishments at an industry showcase. Continue reading
The paper, Stereochemistry and innate immune recognition, opens the door to potential future treatments for sepsis, chronic pain and other conditions that cause inflammation.
The paper’s origins can be traced back nearly 15 years to when CNBP Director Mark Hutchinson began work on a project as a post-doc in the US with Prof Linda Watkins’ team. The goal was to identify the molecular drivers and detection systems involved in causing chronic pain. It began a long journey, in the course of which Mark helped identify one of the detection systems – the Toll Like Receptor 4, or TLR4.
This discovery in turn uncovered a range of other detection and drug action properties of the TLR4 system, including the novel activity of the mirror image structures of a range of chemicals which had previously been thought to lack biological activity.
One of these new discoveries is highlighted in this paper.
For the first time, the mirror image of a well-used receptor blocker, norbinaltorphimine, has been found to be able to block the interaction of TLR4 with MD2, a protein that plays an important part in the body’s immune response.
You can read the paper here.
Journal: FASEB – the Federation of American Societies for Experimental Biology
Publication Title: Stereochemistry and innate immune recognition: (+)-norbinaltorphimine targets myeloid differentiation protein 2 and inhibits toll-like receptor 4 signaling
Authors: Xiaozheng Zhang, Yinghua Peng, Peter M. Grace, Matthew D. Metcalf, Andrew J. Kwilasz, Yibo Wang, Tianshu Zhang, Siru Wu, Brandon R. Selfridge, Philip S. Portoghese, Kenner C. Rice, Linda R. Watkins, Mark R. Hutchinson, and Xiaohui Wang
Abstract: Deregulation of innate immune TLR4 signaling contributes to various diseases including neuropathic pain and drug addiction. Naltrexone is one of the rare TLR4 antagonists with good blood-brain barrier permeability and showing no stereoselectivity for TLR4. By linking 2 naltrexone units through a rigid pyrrole spacer, the bivalent ligand norbinaltorphimine was formed. Interestingly, (+)-norbinaltorphimine ((+)-1) showed ∼25 times better TLR4 antagonist activity than naltrexone in microglia BV-2 cell line, whereas (−)-norbinaltorphimine ((−)-1) lost TLR4 activity. The enantioselectivity of norbinaltorphimine was further confirmed in primary microglia, astrocytes, and macrophages. The activities of meso isomer of norbinaltorphimine and the molecular dynamic simulation results demonstrate that the stereochemistry of (+)-1 is derived from the (+)-naltrexone pharmacophore. Moreover, (+)-1 significantly increased and prolonged morphine analgesia in vivo. The efficacy of (+)-1 is long lasting. This is the first report showing enantioselective modulation of the innate immune TLR signaling.
Key Words: norbinaltorphimine; enantioselective modulation; TLR4; MD-2; morphine analgesia
CNBP Associate Investigators Dr Lyndsey Collins-Praino (University of Adelaide) and Dr Andrew Care (Macquarie University) together with CNBP Director Prof. Mark Hutchinson have been awarded a highly competitive Research Grant by the NeuroSurgical Research Foundation. The funds will help the team to work on pioneering a novel nanotechnology that will look to prevent the spread of Parkinson’s Disease throughout the human brain.
The Australian Research Council (ARC) has announced funding for a super-resolution imaging facility that will be the first of its kind in Australia.
The facility brings together a consortium of multidisciplinary researchers from leading Australian Universities, Institutes and Research Centres (including CNBP) to develop new capacities for materials science, photonics devices, engineering, and neuroscience, microbial and cardiovascular research.
At its core the A$3.0m ARC LIEF project will enable scientists to study the inner workings of cells in their native environment. This represents a step change from currently imaging isolated 2D cells cultured in a petri dish to future research that will reveal subcellular structures and cell-to-cell communications in 3D tissue in real time.
The National Volumetric Imaging Platform, as it is known, will be installed, maintained and operated by the Institute for Biomedical Materials and Devices (IBMD) at the University of Technology Sydney (UTS) and the ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP) at RMIT University in Melbourne. This project is scheduled to be completed in late 2019.
UTS Professor Dayong Jin, Lead Chief Investigator of the project, said that the facility will give scientists a “new way to decode the complexities of life science machinery.”
“High-resolution imaging of the large volume of single cells and functional navigation of their interactions will allow researchers to drop into a ‘street view’ and observe the details of intercellular ‘live traffic’,” he said.
Prof Brant Gibson, Co-Deputy Director and RMIT node director of CNBP said, “I am very excited to lead the RMIT University node of the National Volumetric Imaging Facility and to work in collaboration with Jin Dayong, the UTS node and all of our collaborative institutional partners. This facility will enable us to image deeper within biological samples than we ever been able to before, with nanoscale resolution and extraordinary bandwidth stretching from the near-UV (400nm) well into the infrared (1650nm) spectrum.”
Prof Mark Hutchison, Professor at the Adelaide Medical School and Director of the CNBP at the University of Adelaide said, “This is an exciting development of advanced imaging infrastructure capacity that will allow a convergence of scientists from across the country to gain an unprecedented level of molecular insights into the complex systems and arrangement of cells in biologically relevant complex 3 dimensional environments.”
Participating Organisations include: Universities: University of Technology Sydney, RMIT University, University of Wollongong, University of Sydney, The University of Queensland, The University of New South Wales, Macquarie University, The University of Adelaide.
Institutes and Centres: Institute for Biomedical and Materials Devices, ARC Research Hub for Integrated Device for End-user Analysis at Low-levels, Institute for Molecular Horizons, the Heart Research Institute, ithree Institute, Centre for Translational Neuroscience, Australian Centre for Ecogenomics, ARC Centre of Excellence for Nanoscale BioPhotonics.
CNBP science and it’s translation into exciting new commercial ventures was on show at the ‘Science meets Business’ event held in Brisbane, October 11th, 2018.
The event, coordinated by STA, brought national and international corporate leaders and entrepreneurs, venture capitalists and angel investors together with Australian research and commercialisation pioneers, to help advance activity in the science and translation space.
First CNBP’er to present at the event was Chief Investigator Prof Jeremy Thompson who shared his amazing startup story in establishing the business ‘ART Lab Solutions’. The venture uses advanced reproductive technologies to accelerate the improvement of livestock quality.
Next up was the CNBP inspired start-up ‘MEQ Probe‘. Featuring presenters CNBP Director Prof Mark Hutchinson, Jordy Kitschke (CEO of MEQ Probe) and Susan McDonald (Managing Director of Super Butcher), all three discussed elements of the innovative start-up that offers industry an advanced spectral analysis tool that can objectively measure the quality of meat.
“MEQ is a story of success for the CNBP in bringing science together with business to solve a multi-billion dollar problem of objective meat quality measurement and assessment,” said Prof Hutchinson. “At CNBP we have made a conscious decision to actively solve real-world pain points, and engage entrepreneurs to turn amazing research into companies, of which MEQ Probe is an excellent example.”
A/Prof. Daniel Kolarich, CNBP Chief Investigator at Griffith University who also attended the event noted that, “Science meets Business impressively showed that translation does not necessarily correlate with the initial intention of the innovation – that the sky really is the limit when it comes to maximising return from research.”
Below: Smiles from the MEQ Probe team having completed their case study to an active and interested audience at ‘Science meets Business’.
A new paper with CNBP co-authors Prof Mark Hutchinson, Prof Ewa Goldys and Dr Guozhen Liu demonstrates an amperometric sensing device based on graphene oxide (GO) and structure-switching aptamers for long-term detection of cytokines in a living organism.
Journal: ACS Applied Materials and Interfaces.
Authors: Chaomin Cao, Ronghua Jin, Hui Wei, Wenchao Yang, Ewa M. Goldys, Mark R. Hutchinson, Shiyu Liu, Xin Chen, Guangfu Yang, and Guozhen Liu.
Abstract: Cytokine sensing is challenging due to their typically low abundances in physiological conditions. Nanomaterial fabricated interfaces demonstrated unique advantages in ultrasensitive sensing. Here, we demonstrate an amperometric sensing device based on graphene oxide (GO) and structure-switching aptamers for long-term detection of cytokines in a living organism. The device incorporates a single layer of GO acting as a signal amplifier on glassy carbon electrodes. The hairpin aptamers specific to interferon-γ (IFN-γ), which were loaded with redox probes, are covalently attached to GO to serve as biorecognition moieties. IFN-γ was able to trigger the configuration change of aptamers while releasing the trapped redox probes to introduce the electrochemical signal. This in vivo device was capable of quantitatively and dynamically detecting IFN-γ down to 1.3 pg mL–1 secreted by immune cells in cell culture medium with no baseline drift even at a high concentration of other nonspecific proteins. The biocompatible devices were also implanted into subcutaneous tissue of enteritis mice, where they performed precise detection of IFN-γ over 48 h without using physical barriers or active drift correction algorithms. Moreover, the device could be reused even after multiple rounds of regeneration of the sensing interface.
In exciting grant funding news, ARC Future Fellowships were recently awarded to the following CNBP researchers:
Prof Mark Hutchinson (CNBP Director, pictured) – University of Adelaide. Measuring pain in livestock: mechanisms, objective biomarkers and treatments.
Dr Ivan Maksymov (CNBP Researcher Fellow) – RMIT University. Nonlinear optical effects with low-power non-laser light.
Dr Steven Wiederman (CNBP Associate Investigator) – University of Adelaide. From insects to robots: how brains make predictions and ignore distractions.
The Future Fellowships scheme supports research in areas of critical national importance by giving outstanding researchers incentives to conduct their research in Australia. Each Future Fellow recipient will receive salary and on-cost support for four years, and up to $50,000 in additional funding per year for other essential costs directly related to their project.
Congratulations to all Fellowship recipients who will now be able to further develop and advance their innovative areas of research! Further information on Fellowship projects are available from the ARC web site.