Category Archives: UA

Science on show – what’s on in National Science Week

7 August 2019:

The CNBP and its researchers are taking part in a wide range of activities for National Science Week.

This Thursday 8 August researcher Dr Wei Deng from UNSW Sydney will explain how nanotechnogy is changing how we treat cancer, as part of Inspiring Australia’s Talking Science series.

It will be held at the Max Webber Library, in Blacktown, Sydney. More details here.

On Sunday, 11 August, Adelaide University’s Lyndsey Collins-Praino will host Kids Navigate Neuroscience, an event at which children aged 4-10 can explore how the brain works in a fun and hands-on way by participating in a series of interactive neuroscience exhibits.

You can find out more about the event here. Bookings are essential and can be made through Eventbrite.

On Tuesday 13 August explore medical brain research by joining Dr Lindsay Parker, a researcher at Macquarie University, as she discusses how she is trying to create better medicines for Alzheimer’s, chronic pain and brain cancer, by only targeting the unhealthy cells in the brain.

This event is part of Inspiring Australia’s Talking Science series as part of National Science Week. Bookings available now. Contact details:
Castle Hill Library
The Hills Shire Library Service
Email: libraryseminars@thehills.nsw.gov.au
Phone: 02 9761 4510
https://www.scienceweek.net.au/exploring-medical-brain-research/

There is a fun evening next Friday, 16 August, at the Adelaide Medical School, University of Adelaide, where you can explore the neuroscience of sex, drugs and salsa dancing.

A series of interactive exhibits will address questions such as, what role does the brain play in sexual attraction? Can you salsa dance your way to a healthy brain? How does the brain perceive different flavours when drinking wine, and how can pairing wine with different foods alter this perception?

More details here and bookings are through Eventbrite.

Also next Friday, 16 August, the whole family is invited to see some amazing short videos on a massive screen in a free National Science Week Event hosted by STEMSEL Foundation Braggs Lecture Theatre, University of Adelaide AI Light Science Spectacular.

You will find out how the eye works, how NASA finds planets in other solar systems and how detected the edge of the Universe.

You will also explore light, from nanoscale biophotonics with CNBP research fellow Dr Roman Kostecki to exploring the Universe with Dr Jerry Madakbas, a photonics physicist who builds night vision sensors for NASA.

You can book through Eventbrite.

Also on Friday night:

What role does the brain play in sexual attraction? Can you salsa dance your way to a healthy brain? How does the brain perceive different flavours when drinking wine, and how can pairing wine with different foods alter this perception?

These days, you can’t seem to walk through the aisle of a grocery store without being bombarded by newspaper and magazine headlines touting the latest and greatest breakthrough in neuroscience research. But how can you tell fact from fiction?

Join us for this Big Science Adelaide event, held at the Adelaide Health and Medical Sciences (AHMS) building at the University of Adelaide, where we’ll explore the answers to these questions and many more!

More details at https://www.scienceweek.net.au/neuroscience-at-night/ 
Finally, CNBP researchers will be taking part in Science in the Swamp, a fun, free family festival of science displays, shows and activities on Sunday 18 August in Centennial Park, Sydney.

Join scientists as they show what amazing superpowers you find in nature – super sight, super hearing, super strength and camouflage are only some of the capabilities on show.

Be sure to put on your cape and dress up as your favourite superhero for this great event. You can find out more details here.

Finding a way to shutdown rogue cell replication

24 July 2019:

Almost all cells replace themselves by replicating, but when there are errors in DNA-replication, it can lead to diseases including many cancers.

DNA-replication is complex and involves a host of protein machinery. One of the most important is the protein PCNA, which helps orchestrate the process.

Adelaide University postgraduate student Aimee Horsfall, a member of the ARC Centre of Excellence for Nanoscale Biophotonics (CNBP), was part of the team which analysed the structures of a number of proteins interacting with PCNA.

The work suggests that the 3D shape of these proteins defines how strongly this interaction occurs.

The research is important because, if we can understand what makes the interaction with PCNA stronger, and determine the optimal shape, we can develop a drug that mimics it.

This drug could bind PCNA and stop replication in diseased cells, offering a potential treatment for diseases implicated in erroneous DNA-replication, or as a broad spectrum cancer therapeutic.

Journal: ChemBioChem

Publication Title: Targeting PCNA with peptide mimetics for therapeutic purposes.

Authors: Horsfall AJ, Abell AD, Bruning J.

Abstract: PCNA is an excellent inhibition target to shut down highly proliferative cells and thereby develop a broad spectrum cancer therapeutic. It interacts with a wide variety of proteins through a conserved motif referred to as the PCNA-Interacting Protein (PIP) box. There is large sequence diversity between high affinity PCNA binding partners, with conservation of the binding structure – a well-defined 310-helix. Here, all current PIP-box peptides crystallised with human PCNA are collated to reveal common trends between binding structure and affinity. Key intra- and inter-molecular hydrogen bonding networks which stabilise the 310-helix of PIP-box partners are highlighted, and related back to the canonical PIP-box motif. High correlation with the canonical PIP-box sequence does not directly afford high affinity. Instead, we summarise key interactions which stabilise the binding structure that lead to enhanced PCNA binding affinity. These interactions also implicate the ‘non-conserved’ residues within the PIP-box that have previously been overlooked. Such insights will allow a more directed approach to develop therapeutic PCNA inhibitors.

Keywords: PCNA, peptide mimetics, PIP-box, sliding clamp, DNA replication

Link: https://www.ncbi.nlm.nih.gov/pubmed/31247123

Australia wins ‘bronze’ at global neurophotonics summer school

10 July 2019:

A mini-project to map the hearing capability of zebrafish won Adelaide-based PhD student Mengke Han third prize at global neurophotonics summer school that brought some the world’s brightest minds together in Quebec, Canada in June.

Mengke represented Australia at the Frontiers in Neurophotonics Summer School, where researchers and students spent 10 days discovering the latest advances in live cell optical imaging techniques.

With a focus on the up-close workings of the nervous system, the school combined tutorials and hands-on experiments, delivered by experts in photonics and neuroscience.

“We used a relatively new and very powerful imaging technique called two-photon microscopy, to map the brain and neurons of living zebrafish,” Mengke says.

Mengke’s experiment setup

“Zebrafish are small and transparent so they are a convenient species to study in the lab.

“But everything we learn about zebrafish ear development and function, can be applied to human medicine. We can even test human genes in a zebrafish to see what influence they might have on hearing problems.”

With an undergraduate degree in biology and a master’s in physics, Mengke’s current PhD research looks at the development of voltage-sensitive nanoparticles for real-time monitoring of brain activity.

She is based at the Institute for Photonics and Advanced Sensing (IPAS), School of Physical Sciences, the University of Adelaide. She is also member of the ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP).

Through the looking glass

Mark Hutchinson8 July 2019:

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

Research award for Ms Megan Lim

5 June 2019:  Congratulations to PhD Student Ms Megan Lim who was awarded the Robinson’s Research Institute Prize for Best presentation in the field of reproduction, pregnancy or child health at The Australian Society for Medical Research (ASMR) conference.

Megan’s oral presentation was titled “Investigation of haemoglobin as an antioxidant to reduce reactive oxygen species during the in vitro maturation of moues cumulus-oocyte com.

Megan would like to thank my supervisor Dr Kylie Dunning and lab colleagues for their feedback during her practice talks, and also the Biological Challenges meeting attendees who gave her  helpful insights for her project.  “Thank you for your words of encouragement and support!”

Pop-up science

25 May 2019:

CNBP researchers Dr Georgina Sylvia and Dr Erin Smith (in conjunction with Children’s University Adelaide) have taken their love of science to the public, demonstrating fun-filled experiments to budding young scientists at a ‘pop-up’ event titled ‘The Magic and Wonder of Science’. The event took place as part of the biennial ‘Dream Big Children’s Festival’, held in South Australia, May-June, 2019.

Attendees at the ‘pop-up’ outreach event saw science working in practice as well as real-life applications of differing scientific elements.

“We demonstrated numerous experiments to our audience including creating ‘Elephant’s Toothpaste’. This is a foamy substance caused by the rapid decomposition of hydrogen peroxide,” says Georgina.

“Other experiments included a demonstration of atmospheric pressure with a jar of water, as well as the use of liquid nitrogen to freeze an everyday egg in a fry-pan. We wanted to inspire our young audience and to open their minds to the everyday science that exists all around them,” she says.

“Our show aimed to be a blend of entertainment and education with plenty of humor and laughs as well.”

Below – Erin and Georgina putting on their scientific show!

 

Hemoglobin and its role in the oocyte and early embryo

6 May 2019:

Hemoglobin expression in reproductive cells and the role of hemoglobin on oocyte and early embryo development is the focus of this latest CNBP review paper published in the journal ‘Biology of Reproduction’ (lead author Megan Lim based at the University of Adelaide).

Journal: Biology of Reproduction.

Publication title: Hemoglobin: potential roles in the oocyte and early embryo.

Authors: Megan Lim, Hannah M Brown, Karen L Kind, Jeremy G Thompson, Kylie R Dunning.

Abstract: Hemoglobin (Hb) is commonly known for its capacity to bind and transport oxygen and carbon dioxide in erythroid cells. However, it plays additional roles in cellular function and health due to its capacity to bind other gases including nitric oxide. Further, Hb acts as a potent antioxidant, quenching reactive oxygen species. Despite its potential roles in cellular function, the preponderance of Hb research remains focused on its role in oxygen regulation. There is increasing evidence that Hb expression is more ubiquitous than previously thought, with Hb and its variants found in a myriad of cell types ranging from macrophages to spermatozoa. The majority of non-erythroid cell types that express Hb are situated within hypoxic environments, suggesting Hb may play a role in hypoxia-inducible factor (HIF)-regulated gene expression by controlling the level of oxygen available or as an adaptation to low oxygen providing a mechanism to store oxygen. Oocyte maturation and preimplantation embryo development occur within the low oxygen environments of the antral follicle and oviduct/uterus, respectively. Interestingly, Hb was recently found in human cumulus and granulosa cells and murine cumulus-oocyte complexes (COCs) and preimplantation embryos. Here, we consolidate and analyze the research generated to-date on Hb expression in non-erythroid cells with a particular focus on reproductive cell types. We outline future directions of this research to elucidate the role of Hb during oocyte maturation and preimplantation embryo development and finally, we explore the potential clinical applications and benefits of Hb supplementation during the in vitro culture of gametes and embryos.

Collaborative research visit to Peking University

April 2019

CNBP PhD Student Ms Yuan Qi Yeoh enjoyed a two week collaborative visit with Prof Xuefeng Guo’s team at Peking University. Working with Peking University PhD student Xinjiani Chen on a  research project involving the molecular dynamics of the secondary structure of a cyclic photoswitchable peptide.

Yuan Qi had the opportunity to participate in the fabrication process of the single-molecule devices. Specifically, they carried out temperature-dependent experiments using their advanced facilities to probe the molecular dynamics of the secondary structure upon photoswitching.

Yuan Qi says that “It was a great opportunity to collaborate with colleagues at Peking University in such high impact research and enjoyed working in their sophisticated research labs”

New method to functionalise glass fibers

17 April 2019:

One of the biggest challenges associated with exposed core glass optical fiber-based sensing is the availability of techniques that can be used to generate reproducible, homogeneous and stable surface coating. CNBP scientists report a one step, solvent free method for surface functionalization of exposed core glass optical fiber that allows for the binding of fluorophore-of-choice for metal ion sensing.

Lead author of the paper, published in the journal ‘Sensors’, is CNBP researcher Dr Akash Bachhuka based at the University of Adelaide.

Journal: Sensors

Publication TitleSurface Functionalization of Exposed Core Glass Optical Fiber for Metal Ion Sensing;

Authors: Akash Bachhuka, Sabrina Heng, Krasimir Vasilev, Roman Kostecki, Andrew Abell and Heike Ebendorff-Heidepriem

Abstract:

One of the biggest challenges associated with exposed core glass optical fiber-based sensing is the availability of techniques that can be used to generate reproducible, homogeneous and stable surface coating. We report a one step, solvent free method for surface functionalization of exposed core glass optical fiber that allows achieving binding of fluorophore of choice for metal ion sensing. The plasma polymerization-based method yielded a homogeneous, reproducible and stable coating, enabling high sensitivity aluminium ion sensing. The sensing platform reported in this manuscript is versatile and can be used to bind different sensing molecules opening new avenues for optical fiber-based sensing.

Ruthenium-based sensor detects nitric oxide

8 February 2019:

In a new publication, a responsive Ruthenium-based luminescence sensor was employed as a molecular probe for detecting nitric oxide (NO). The research suggests potential clinical utility for the measurement of soluble NO in the circulation system and possibly tissue. Lead authors of this paper are CNBP’s Dr Achini Vidanapathirana and Benjamin Pullen (both based at SAHMRI).

Journal: Scientific Reports.

Publication title:  A Novel Ruthenium-based Molecular Sensor to Detect Endothelial Nitric Oxide.

Authors: Achini K. Vidanapathirana, Benjamin J. Pullen, Run Zhang, MyNgan Duong, Jarrad M.Goyne, Xiaozhou Zhang, Claudine S. Bonder, Andrew D.Abell, Christina A. Bursill, Stephen J. Nicholls & Peter J. Psaltis.

Abstract: Nitric oxide (NO) is a key regulator of endothelial cell and vascular function. The direct measurement of NO is challenging due to its short half-life, and as such surrogate measurements are typically used to approximate its relative concentrations. Here we demonstrate that ruthenium-based [Ru(bpy)2(dabpy)]2+ is a potent sensor for NO in its irreversible, NO-bound active form, [Ru(bpy)2(T-bpy)]2+. Using spectrophotometry we established the sensor’s ability to detect and measure soluble NO in a concentration-dependent manner in cell-free media. Endothelial cells cultured with acetylcholine or hydrogen peroxide to induce endogenous NO production showed modest increases of 7.3 ± 7.1% and 36.3 ± 25.0% respectively in fluorescence signal from baseline state, while addition of exogenous NO increased their fluorescence by 5.2-fold. The changes in fluorescence signal were proportionate and comparable against conventional NO assays. Rabbit blood samples immediately exposed to [Ru(bpy)2(dabpy)]2+ displayed 8-fold higher mean fluorescence, relative to blood without sensor. Approximately 14% of the observed signal was NO/NO adduct-specific. Optimal readings were obtained when sensor was added to freshly collected blood, remaining stable during subsequent freeze-thaw cycles. Clinical studies are now required to test the utility of [Ru(bpy)2(dabpy)]2+ as a sensor to detect changes in NO from human blood samples in cardiovascular health and disease.