Monthly Archives: July 2019

5 ways nanoscale biophotonics could help your family

30 July 2019:

Biophotonics is a technique with so many applications it’s hard to know where to start.
While you probably have never heard of most of them, the technology is transforming the way we study human health.

Improving pregnancy success rates

A lot of what we know about fertilisation and embryo development has come from in vitro experiments – those carried out in a test tube. How much better if we could observe these processes inside real, live female bodies.

Well new technologies, using nanoscale biophotonics, let us do precisely that.

High powered sensors, harnessing the power of light, can zoom in on the chemistry of pregnancy to deepen our understanding of all the ingredients needed to grow a healthy baby for nine months.

Safer brain surgery

The tiny imaging probe, encased within a brain biopsy needle, lets surgeons “see” at-risk blood vessels as they insert the needle. That helps stop potentially fatal bleeds.

The smart needle, being developed by CNBP researchers at the University of Adelaide, contains a tiny fibre-optic camera, the size of a human hair, shining infrared light to see the vessels before the needle can damage them.

The needle is connected to computer software that can alert the surgeon in real-time.
It has already gone through a pilot trial with 12 patients at Sir Charles Gairdner Hospital in Western Australia and will soon be ready for formal clinical trials.

Early diagnosis of common health problems

Our cells often signal ill health long before symptoms appear. And as we all know, early diagnosis can often mean the difference between life and death.

That inspired CNBP researchers to look for a general marker for ill health and then to work on a means of detecting it.

They settled on the cytokines, a type of protein secreted by cells in the immune system that can signal a whole range of conditions including arthritis, tissue trauma, depression or even cancer.

The problem up to now has been that cytokines are extremely hard to measure and quantify – there is not many of them at any time, they are extremely small and exist in an environment of much background noise and interference.

So CNBP researchers developed nanotools to monitor cytokines in living humans. They engineered the surfaces of nanomaterials such as gold nanoparticles, graphene oxides and magnetic nanoparticles to sense the presence of cytokines, providing an ultra-powerful tool for early detection.

Removing more cancer cells the first time

One of the biggest problems for cancer surgeons is making sure they remove all the cancer cells while leaving as much healthy tissue intact as possible. But it can be hard to tell the two apart – in 15-20% of cases the patient requires follow-up surgery to remove tumour tissue that was missed the first time. It is particularly difficult to differentiate with breast cancer.

Now CNBP researchers, in collaboration with clinicians at the Royal Adelaide Hospital, have developed a sensor which can potentially help surgeons to tell the difference between healthy and cancerous tissue in real time, which could significantly increase the surgery success rate for many cancers.

The probe works by measuring the pH of the surface of the tissue, an indicator of whether the tissue is healthy or tumorous. The tip of an optical fibre is coated with a pH sensitive indicator, and the signal read out uses a low-cost light emitting diode and portable spectrometer.

Less painful, more accurate testing for prostate cancer

It has long been a goal to replace invasive needle biopsies to test for prostate cancer with a simple urine test. Not only would that be great for the patients, it would also be cheaper and faster. But current urine diagnostic tools are just not sensitive enough.

For a test to be useful for early diagnosis and treatment, it would need to detect just 10 cancer cells in a large volume of urine. Biophotonics could solve this problem.

CNBP is working with Minomic International and Macquarie University to develop a new method of fluorescent staining and imaging prostate cancer cells so they become highly visible, glowing when viewed under a special microscope.

The capacity to quantify single prostate cancer cells has the potential to revolutionise the diagnostics industry.

Shedding light on nanoparticles for better bio-imaging

25 July 2019:

CNBP researcher Dr Nafisa Zohora has been awarded her PhD in applied physics by Melbourne’s RMIT University. Her research project looked at materials that could be used as an alternative to available fluorophores – the fluorescent chemical compounds used in a variety of biological research projects.

The discoveries of the project solves a significant problem that was stopping scientists obtaining good images of biological samples.

Fluorophores are used to stain specific cells, for example, which are then observed and analysed by a fluorescence microscope. They are used as biomarkers to identify a range of bioactive molecules such as antibodies or proteins.

But for the fluorophores to re-emit light, they must first absorb it in a process known as “excitation” – usually brought about with a laser.

The problem is, though, that some compounds just do not absorb enough with low power excitation to produce enough fluorescence to be seen under the microscope. But higher power, from greater exposure to a laser for example, can also generate so much heat that the sample is destroyed.

The fluorophores are also inclined to lose their ability to emit within a few seconds with repeated exposure to the laser, not giving enough time to take a good image.

Nafisa set out to find a solution to both these issues. She began by studying the commercially available nanoparticle fluorophores such as cuprous oxide (Cu2O), titanium dioxide (TiO2) and zinc oxide (ZnO) but couldn’t find the properties she was looking for.

She then decided to synthesise her own nanoparticles.

After two years of hard work, she had successfully developed a methodology to synthesis Cu2O nanocubes that become very bright with a very low power excitation.

What’s more they are photostable for several hours under repeated exposure to a laser – so both problems solved!

In a follow-up collaboration with the University of Adelaide, Nafisa tested the nanoparticles for their toxicity to cells, giving them a clean bill.

Her work uncovering the exceptional properties of the synthesised Cu2O nanoparticles opens up new possible applications in detecting antigens and other long-term bio-imaging applications.

Nafisa’s supervisors were Professor Brant Gibson (Physics, RMIT University), Dr Ahmad Kandjani (Chemistry, RMIT University) and Professor Mark Hutchinson (The University of Adelaide). She completed her PhD on 1 July 2019, and her graduation ceremony will be in December.

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

CNBP research wins Young Scientist Award

18 July 2019:

CNBP research fellow Dr Lindsay Parker, of Macquarie University, has won an award for the best research paper from an investigator under 40, at an international conference in Rome.

Lindsay’s work is aimed at better understanding molecules ex-pressed in the brain during pain, brain diseases and brain cancer. This could lead to improved precision drugs that specifically target only the unhealthy cells in the brain.

She won a “Young Scientist Award” at the 41st PIERS (Photonics & Electromagnetics Research Symposium) held at the University of Rome in June.

Her paper, “Utilising Glycobiology for Fluorescent Nanodiamond Uptake and Imaging in the Central Nervous System” was in the category “Remote Sensing, Inverse Problems, Imaging, Radar & Sensing”.

The paper, in collaboration with RMIT University and the University of Colorado Boulder, investigated the ability of lectin-coated fluorescent nanodiamonds to recognise specific central nervous system cell types.

The prize included cash, and an invitation to the Symposium Banquet held at Palazzo Brancaccio. Lindsay also received travel awards from MQ University Primary Carer Support for Conference Attendance ($2000) and MQ Research Centre for Diamond Science and Technology ($1000) which meant her partner and baby William were also able to be in Rome with her as she worked.

While she was in Europe, Lindsay took the opportunity to give invited talks at the Czech Academy of Sciences in Prague and at the University of Groningen in Netherlands while visiting two other labs working in similar research areas to her synthetic nanochemistry expert Dr Petr Cigler and nanobiotechnology expert A/Prof Romana Schirhagl.

Diamonds improve orthopaedic implants

17 July 2019:

3D printing of titanium has made patient-specific orthopaedic implants possible, promising to dramatically improve many people’s quality of life.

But, despite the huge potential, there are still significant problems to overcome, particularly in how the implants integrate with human tissue and bone.

Associate Professor Kate Fox from RMIT University in Melbourne, an Associate Investigator with the CNBP, led the team which, in a previous study, showed that a thin film coating of diamond could provide a better surface for cells to interact.

A new paper, Engineering the Interface: Nanodiamond Coating on 3D-Printed Titanium Promotes Mammalian Cell Growth and Inhibits Staphylococcus aureus Colonization expands on that work.

It describes how applying a nanodiamond (ND) coating on to the 3D printed titanium increased the cell density of both skin bone cells after three days of growth compared to the uncoated 3D printed titanium.

The study also showed an 88% reduction of Staphylococcus aureus – or Golden Staph – adherence to ND-coated substrates compared to those without.

This study, whose lead author is Aaquil Rifai, from RMIT, paves a way to create antifouling structures for biomedical implants.

You can read the paper here.

Journal: ACS Applied Materials & Interfaces

Publication Title:  Engineering the Interface: Nanodiamond Coating on 3D-Printed Titanium Promotes Mammalian Cell Growth and Inhibits Staphylococcus aureus Colonization

Authors: Aaqil Rifai*, Nhiem Tran, Philipp Reineck, Aaron Elbourne, Edwin Mayes, Avik Sarker, Chaitali Dekiwadia, Elena P. Ivanova, Russell J. Crawford, Takeshi Ohshima, Brant C. Gibsonm, Andrew D. Greentree, Elena Pirogova, and Kate Fox*

Abstract:  Additively manufactured selective laser melted titanium (SLM-Ti) opens the possibility of tailored medical implants for patients. Despite orthopedic implant advancements, significant problems remain with regard to suboptimal osseointegration at the interface between the implant and the surrounding tissue. Here, we show that applying a nanodiamond (ND) coating onto SLM-Ti scaffolds provides an improved surface for mammalian cell growth while inhibiting colonization of Staphylococcus aureus bacteria. Owing to the simplicity of our methodology, the approach is suitable for coating SLM-Ti geometries. The ND coating achieved 32 and 29% increases in cell density of human dermal fibroblasts and osteoblasts, respectively, after 3 days of incubation compared with the uncoated SLM-Ti substratum. This increase in cell density complements an 88% reduction in S. aureus detected on the ND-coated SLM-Ti substrata. This study paves a way to create facile antifouling SLM-Ti structures for biomedical implants.

Key Words: nanodiamond, antifouling, 3D printing, biomaterial, implants

What is Nanoscale Biophotonics?

15 July 2019:

Researchers at the ARC Centre of Excellence for Nanoscale BioPhotonics have an early hurdle to jump when trying to explain their research to friends, family and the general public.

What on earth is nanoscale biophotonics?

While nothing about the field could exactly be called “simple”, it does become easier to understand when we realise that light can be put to some unusual uses.

And in biophotonics, that is as a tool to measure and detect all manner of things, from the genes that give away the presence of a pathogen, to chemicals released as part of our bodies reactions to the environment, and the fatty deposits that could mean you are at risk of a heart attack.

Dr Georgina Sylva, a recent winner of a A$20,000 #STEMstart grant, simplifies matters by breaking the definition of “nanoscale biophotonics” down for us.

“Nanoscale means things that are on a really, really tiny scale. Things that are a nanometre in size”.

At that scale (and a nanometre is equal to one billionth of a metre) it is way beyond the limitations of an ordinary microscope to see – and that’s where light comes in.

“Biophotonics refers to studying and understanding biology using light,” says Georgina.

“Photonics is how we play with light and how we use light. We are able to use the properties of light – the way that it can act as a particle or a wave to see very small things – to detect, to sense, to image, to measure things.

“Nanoscale biophotonics allows us to get a really good close-up image of what’s happening in a biological environment. The whole point of that is to understand how we can solve biological problems.”

Until nanoscale biophotonics, we have been in the dark about much of the activity inside human cells because we didn’t have the right technology to see them. But by using light we can measure almost anything – the chemicals released at the precise moment a human egg is fertilised, for example, or the Ph of a baby’s blood during birth to detect the risk of oxygen deprivation.

Just as astronomy’s Hubble Telescope has allowed us to suddenly view exoplanets and distant galaxies, nanoscale biophotonics has revealed our “inner space”, a new world for scientists to explore.

So, what are the applications of nanoscale biophotonics, and how might this field influence health and medicine? Read our next blog post How nanoscale biophotonics is already making our lives better.

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.