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

Shedding light on golden staph

3 July 2019:

A groundbreaking new technique will slash the time it takes to detect potentially lethal golden staph infection from two days to just two hours.

Researchers from the ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP) targeted the bacterium with a luminescent DNA probe.

“This allows us to find the “needle in the haystack” because only the “needle” lights up,” says Dr Nima Sayyadi, Research Fellow at the Macquarie University node of the CNBP and lead author on the paper.

Golden staph, or Staphylococcus aureus, lives on the skin or in the nose. It is usually harmless, but if it enters the skin through a cut it can cause a range of infections, which in some cases are fatal.

Dr Nima Sayyadi in the lab

In the most at-risk patients, such as the elderly, it is vital to identify the infection and begin treatment with appropriate antibiotics as soon as possible. However, current identification techniques require culturing cells for up to two days to provide a positive infection result.

The new approach, known as Time-Gated Luminescent in Situ Hybridization (LISH), takes just two hours and could have a range of other applications. While it cannot yet separately identify drug resistance strains of golden staph, researchers are working on it.

CNBP scientists are also working on a range of transformational research projects based on the luminescence based detection of single cells in human body fluid samples, which will help them label antibodies and molecules as well as DNA.

“We’ve also done work in prostate cancer and bladder cancer where the target cell can be quickly and easily identified in urine samples,” says Project Lead and CNBP node leader at Macquarie University, Professor James Piper AM.

The research was reported in the journal Molecules, which you can read here.

Luminescent In Situ Hybridization (LISH)

Nanodiamonds are a wound’s best friend

2 July 2019, By Amanda Abraham.

Band-aids and bandages are remarkable. A simple invention allows us to cover, treat and protect injuries until they have time to heal. But they come with a big drawback – the only way we can check how well the wound is healing, is by removing them.

This means that sometimes infections are detected only after they take hold, which can lead to increased recovery times and the need for additional medications and care.
Now imagine a technology that enables us to track the healing process without needing to remove the bandage.

This technology is being worked on by a group of CNBP researchers based at RMIT University who presented their research at a Physics in the Pub event held in Hawthorn last week.

The CNBP team in action at Physics in the Pub. The costume is a finger!

The team explained that by using nanodiamonds in a ‘smart dressing’, researchers are able to detect temperature changes within or surrounding a wound – a common indication of infection – without removing the bandage.

This would give doctors and nurses the ability to track the healing progress without having to remove and re-apply the dressing.

Dr Amanda Abraham, who presented alongside Qiang Sun, Daniel Stavrevski and Donbi Bai, explained that the topic was chosen because “almost everyone has experienced the pain of band-aid removal. Using nanodiamonds could save the patient further discomfort, and speed up the healing process by providing treatment only when needed.”

Physics in the Pub is an informal, light-hearted night where physicists, astronomers, theoreticians, engineers and educators share their love of science over a refreshing beverage. The event is supported by the AIP, and ARC Centres of Excellence CNBP, OzGrav, FLEET and Exciton Science.

New probe to detect hydrogen peroxide

10 June 2019:

A team of CNBP researchers have published a new paper discussing the design and application of a micro fabricated needle-like probe to measure hydrogen peroxide.  This new microfluidic tool has applications for monitoring dynamic chemical reactions in analytical chemistry and biological systems.

Journal: RSC Advances

Publication Title: Microfabricated needle for hydrogen peroxide detection

Authors: Shilun Feng, Sandhya Clement, Yonggang Zhu, Ewa M. Goldys and David W. Inglis

Abstract:  A microfabricated needle-like probe has been designed and applied for hydrogen peroxide (H2O2) sampling and detection using a commercial, single-step fluorescent H2O2 assay. In this work, droplets of the assay reagent are generated and sent to the needle tip using a mineral-oil carrier fluid. At the needle tip, the sample is drawn into the device through 100 mm long hydrophilic capillaries by negative pressure. The sampled fluid is immediately merged with the assay droplet and carried away to mix and react, producing a sequence of droplets representing the H2O2 concentration as a function of time. We have characterized the assay fluorescence for small variations in the sample volume. With the calibration, we can calculate the concentration of H2O2 in the sampled liquid from the size and intensity of each merged droplet. This is a microfluidic data-logger system for on-site continuous sampling, controlled reaction, signal storage and on-line quantitative detection. It is a useful tool for monitoring dynamic chemical reactions in analytical chemistry and biological applications.

Key words: Microfluidics, probe, H2O2, analytics chemistry

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!”

What is the potential for CRISPT/Cas Multiplex Biosensing?

29 May 2019:

Recent publication by CNBP PhD student Mr Yi Li and team at the University of New South Wales explores the challenges and opportunities of working with CRISPR /Cas for multiplex detection

Journal: Trends in Biotechnology

Publication TitleCRISPR/Cas Multiplexed Biosensing: A Challenge or an Insurmountable Obstacle?

Authors: Yi Li, Linyang Liu, Guozhen Liu

Abstract:  Performing multiplex detection is still an elusive goal for molecular diagnostics. CRISPR/Cas-based biosensing has demonstrated potential for multiplex detection. Instead of being an insurmountable obstacle, CRISPR/Cas multiplexed biosensing is a realistic challenge with some recent successful applications. Strategic considerations are required to fully explore its potential in multiplex diagnostics.

Key Words:

CRISPR/Cas; multiplex; biosensing; diagnostics; nucleic acid detection

 

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!

 

Cancer research to the public

20 May 2019:

CNBP AI at Macquarie University and Early Career Fellow at the Cancer Institute NSW, Dr Andrew Care, has presented his research to a packed house at a ‘Pint of Science’ public outreach and engagement event, 20th May 2019.

Held at the Nags Head Hotel, Glebe, Sydney, Dr Care talked about the latest in cancer research with a particular focus on a newly discovered class of biologically-derived nanoparticles (protein nanocages), and how they can be genetically-engineered to target and destroy tumours.

“Taking my science out to the public was great fun,” he says. “But more importantly it was a good opportunity to highlight that positive advances we are making in the fight against disease thanks to ongoing research investment in Australia,” he said.

Dr Care added, “I checked out Pint of Science for the first time last year. I saw a great talk by Dr Orazio Vittorio a cancer biologist from Children’s Cancer Institute Australia. After a chat at the pub about our research, we started a collaboration. A year later Orazio and I are developing an exciting new tool for cancer treatment! Together, we’ve also obtained research funding, and we’re about to file a patent and to publish our first paper together. None of this would have possible without Pint!”

“Talking at Pint of Science this year is my way of giving back and saying thanks for making a great collaboration happen…and maybe to find another awesome collaborator lurking in the pub again,” he concludes.

Dr Care’s research group combines techniques from synthetic biology and nanomedicine for the targeted treatment of cancer. More information on his exciting work can be found in his profile here.

Below – Dr Care presenting his research at Pint of Science, Sydney 2019.

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.