Category Archives: UA

Cell surface sensors could advance precision medicine

1 October 2019:

Researchers have found a way to identify multiple cell signalling proteins using a single cell rather than the billions of cells used previously.

The new measurement technology, developed by researchers at the ARC Centre of Excellence for Nanoscale Biophotonics, brings precision medicine a step closer.

“Cells secrete various messenger molecules, such as cytokines. They may indicate the presence of a disease or act as a driver of key therapeutic effects,” says Dr Guozhen Liu, lead author of paper detailing the technology.

The method, termed OnCELISA, uses antibodies attached on specially engineered cell surfaces to capture cytokine molecules before they have a chance to disperse away from the cell.

The secreted messenger proteins such as cytokines are reported, at the single cell level, by using fluorescent magnetic nanoparticles.

Cytokines secreted from cells play a critical role in controlling many physiological functions, including immunity, inflammation, response to cancer, and tissue repair.

 

The image represents our sensor during the process of detecting cytokine molecules being secreted from cells. The sensor is represented by a pair of Y-shaped antibodies, the capture antibody (purple stem) and the detection antibody (pink stem).

The OnCELISA system can be used for ultrasensitive monitoring of cytokine release by individual cells, and it can also help discover cell populations with therapeutic value.

“The ability to identify and select cell populations based on their cytokine release is particularly valuable in commercial cell technologies and it can help develop unique products, such as future non-opioid pain relief” says Dr Liu.

“Importantly, our design uses commercially available reagents only, so it can be easily reproduced by others,” she adds.

While the published work focuses on specific proinflammatory cytokines IL-6 and IL-1β, the method is potentially suitable for a broad range of other secreted proteins and cell types.

The new technique represents an advance on traditional methods such as the enzyme-linked immunosorbent assays (ELISA) that detect average levels of secreted molecules from cell ensembles.

The OnCELISA takes the ELISA approach to its absolute extreme, by detecting cytokines on the surface of individual, single live cells.

The publication has been reported by prestigious iScience journal and can be found at https://www.sciencedirect.com/science/article/pii/S2589004219303578.

Journal: iScience

Publication Title: A Nanoparticle-Based Affinity Sensor that Identifies and Selects Highly Cytokine-Secreting Cells

Authors: Guozhen Liu; Christina Bursill; Siân P.Cartland; Ayad G.Anwer; Lindsay M.Parker; Kaixin Zhang; Shilun Feng; Meng He; David W.Inglis; Mary M.Kavurma; Mark R.Hutchinson; Ewa M.Goldys

Summary: We developed a universal method termed OnCELISA to detect cytokine secretion from individual cells by applying a capture technology on the cell membrane. OnCELISA uses fluorescent magnetic nanoparticles as assay reporters that enable detection on a single-cell level in microscopy and flow cytometry and fluorimetry in cell ensembles. This system is flexible and can be modified to detect different cytokines from a broad range of cytokine-secreting cells. Using OnCELISA we have been able to select and sort highly cytokine-secreting cells and identify cytokine-secreting expression profiles of different cell populations in vitro and ex vivo. We show that this system can be used for ultrasensitive monitoring of cytokines in the complex biological environment of atherosclerosis that contains multiple cell types. The ability to identify and select cell populations based on their cytokine expression characteristics is valuable in a host of applications that require the monitoring of disease progression.

Link: https://doi.org/10.1016/j.isci.2019.09.019

Science by the Sea 2019

23 September 2019:

By Patrick Capon and Kathryn Palasis

The current academic landscape demands ‘Publish or Perish’, but how do you make sure your publication stands out from the rest? Luckily for us, CNBP has identified this issue and developed a residential masterclass with a dual purpose of giving young researchers the opportunity to workshop a range of different manuscripts while growing team culture. Continue reading

Prestigious research award for emerging fertility leader

26 August 2019: 

Dr Kylie Dunning is motivated by creating a world where fewer couples struggle with infertility, an often invisible and stigmatised health challenge facing more than 15% of Australian couples. With lived experience herself of the challenges of starting a family, Dr Dunning is paving the way for couples to experience better, and more effective fertility care, through the creation of exciting new technologies. Continue reading

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!