All posts by AJ Epstein

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.