News Article | February 20, 2017
Researchers at The University of Queensland's Australian Institute for Bioengineering and Nanotechnology (AIBN) have designed a virus-like nanoparticle (VNP) that delivers drugs directly to the cells where they are needed. The lead author of a paper on the topic, Dr Frank Sainsbury, said the VNP was made from the structural proteins that formed the virus's protective shell. "Viruses have evolved to contain and protect bioactive molecules," Dr Sainsbury said. "They've also evolved smart ways to get into cells and deliver these bioactive molecules. "The VNP is an empty shell. It looks like a virus but it's not infectious. This makes it safe to use as a targeted drug delivery system." With infectious viral genes removed, empty shells can be loaded with small molecules or proteins resulting in a stable, well-protected therapeutic package. The outside of the shell then determines where the package will go. The ability to send drugs directly to their target is a critical goal in the development of safe, effective therapeutics. Currently many drugs, including anti-cancer chemotherapies, must be administered at high doses in order to have a therapeutic effect. This can lead to harsh side effects because drugs can damage healthy cells as well as intended targets. Dr Sainsbury and his colleagues developed a VNP using the Bluetongue virus, which normally infects cows, sheep and other ruminants. They picked the virus because of its stable shell, made of hundreds of proteins that are known to bind to a molecule found in high levels around many cancer cells. Dr Sainsbury teamed up with Dr Michael Landsberg at UQ's School of Chemistry and Molecular Biosciences and researchers at the Institute for Molecular Bioscience and the UK's John Innes Centre. They were able to demonstrate that the porous VNPs could be filled with small molecules for drug delivery and it also was possible to design VNPs to contain larger molecules, such as therapeutic proteins. Importantly, the researchers showed VNPs were able to bind to breast cancer cells, and then be absorbed. Dr Sainsbury said the next step was to load the VNPs with anti-cancer drugs and see if they could kill cancer cells without harming healthy cells. Although VNPs are highly complex and difficult to synthesise, Dr Sainsbury said they could be easily produced in the leaves of Nicotiana benthamiana, a wild relative of tobacco. By providing plant cells with genetic instructions for making VNPs, the plant was able to assemble virus protein shells without any permanent change to the plant's own genetic code. Dr Sainsbury said one day greenhouses may be able to produce large amounts of the nanoparticles within days. "This research unlocks a myriad of potential applications in therapeutic delivery," Dr Sainsbury said. Because the nanoparticles they have designed are highly stable, the AIBN research team is exploring other biotechnology applications. Explore further: Plant-made virus shells could deliver drugs directly to cancer cells
News Article | April 13, 2016
School of Biomedical Sciences researcher Dr Richard Clark said marine snail venom was a well-known and promising source of new pain drugs, but substantial hurdles had restrained progress. "Translating the venom's toxins into a viable drug has proved difficult," Dr Clark said. "But now we've been able to identify a core component of one of these conotoxins (toxins from cone snail venom) during laboratory tests. "We think this will make it much easier to translate the active ingredient into a useful drug." Dr Clark said a sea snail used its venom to immobilise prey and protect itself. "The venom's analgesic properties have been well researched," he said. "In this study, we've been able to shrink a particular conotoxin to its minimum necessary components for the pain relief properties to continue to work. "Using a laboratory rat model, we used the modified conotoxin to successfully treat pain generated in the colon, similar to that experienced by humans with irritable bowel syndrome. "Although the conotoxin has been modified, its pain relief properties remained as effective as the full-size model. "Simplifying the conotoxin will make a drug much faster and cheaper to develop." Dr Clark said further research was under way to improve the modified conotoxin's stability and to test its ability to treat other types of pain. The research, published in Angewandte Chemie International Edition, was undertaken in collaboration with Professor David Craik at UQ's Institute for Molecular Bioscience, Professor David Adams at the Royal Melbourne Institute of Technology and Associate Professor Stuart Brierley at the University of Adelaide. Explore further: Cone snails and plants used to develop oral drug for pain More information: Bodil B. Carstens et al. Structure-Activity Studies of Cysteine-Rich α-Conotoxins that Inhibit High-Voltage-Activated Calcium Channels via GABA Receptor Activation Reveal a Minimal Functional Motif , Angewandte Chemie International Edition (2016). DOI: 10.1002/anie.201600297
News Article | February 22, 2017
IMB Centre for Superbug Solutions Deputy Director Associate Professor Lachlan Coin said arming clinicians with this information could help them prescribe the most effective antibiotic for their patient. "Antibiotic resistance is a global challenge that threatens our ability to treat common infections," he said. "Sequencing a bacterial genome using standard techniques resulted in a genome splitting into hundreds of fragments which was impossible to piece together. "In particular, pathogenicity islands—which are crucial to identifying antibiotic resistance—usually split across multiple pieces. "For the past two years, we have used cutting-edge Oxford Nanopore Technologies sequencing devices to sequence bacterial genomes and understand how antibiotic resistance develops. "Because this technology is so new, we needed to develop a powerful method that could help us make the most of its results and really understand the genetic drivers of antibiotic resistance," Associate Professor Coin said. IMB Postdoctoral Researcher Dr Minh Duc Cao said the team developed a new method for analysis of sequencing data on the fly, which allowed them to quickly and accurately piece together complete genomes. "With our method, we can reconstruct an entire bacterial genome shortly after you switch on the machine and put in the DNA sample. "The speed is key as we're interested in predicting antibiotic resistance in real time on clinical samples, because when it comes to diagnosing and treating infections, every minute counts," he said. Associate Professor Coin said the method could be applied to help unravel the genomic causes of other diseases. "We would like to work towards finding new ways to apply this approach to help unravel other diseases, particularly cancer. "Cancer genomes are about 1000 times larger than bacterial genomes, so the powerful combination of this leading technology and our improved method holds enormous potential for rapid assembly of personalised tumour genomes," Associate Professor Coin said. The research was published in Nature Communications and was funded by The University of Queensland, National Health and Medical Research Council and the Australian Research Council. The University of Queensland's Institute for Molecular Bioscience Centre for Superbug Solutions will host the Solutions for Drug-Resistant Infections conference in Brisbane from 3-5 April 2017. The conference will bring international experts and advocates in the field to network and discuss new ways to solve the global challenge of drug-resistant infections. More information: Minh Duc Cao et al. Scaffolding and completing genome assemblies in real-time with nanopore sequencing, Nature Communications (2017). DOI: 10.1038/ncomms14515
News Article | February 8, 2017
Australian researchers are a step closer to understanding immune sensitivities to well-known, and commonly prescribed, medications. Many drugs are successfully used to treat diseases, but can also have harmful side effects. While it has been known that some drugs can unpredictably impact on the functioning of the immune system, our understanding of this process has been unclear. The team investigated what drugs might activate a specialised type of immune cell, the MAIT cell (Mucosal associated invariant T cell). They found that some drugs prevented the MAIT cells from detecting infections (their main role in our immune system), while other drugs activated the immune system, which may be undesirable. The results, published in Nature Immunology overnight, may lead to a much better understanding of, and an explanation for, immune reactions by some people to certain kinds of drugs. The findings may also offer a way to control the actions of MAIT cells in certain illnesses for more positive patient outcomes. The multidisciplinary team of researchers are part of the ARC Centre of Excellence in Advanced Molecular Imaging, and stem from Monash University, The University of Melbourne and The University of Queensland. Access to national research infrastructure, including the Australian synchrotron, was instrumental to the success of this Australian research team. Dr Andrew Keller from Monash University's Biomedicine Discovery Institute said that T cells are an integral part of the body's immune system. "They protect the body by 'checking' other cells for signs of infection and activating the immune system when they detect an invader," he said. "This arrangement is dependent on both the T cells knowing what they're looking for, and the other cells in the body giving them useful information." PhD student Weijun Xu from The University of Queensland's Institute for Molecular Bioscience used computer modelling to predict chemical structures, drugs and drug-like molecules that might impact on MAIT cell function. Such small compounds included salicylates, non-steroidal anti-inflammatory drugs like diclofenac, and drug metabolites. University of Melbourne Dr Sidonia Eckle from the Peter Doherty Institute for Infection and Immunity said the implications point to possible links between known drug hypersensitivities and MAIT cells. "A greater understanding of the interaction between MAIT cells and other host cells will hopefully allow us to better predict and avoid therapeutics that influence and cause harm," she said. "It also offers the tantalising prospect of future therapies that manipulate MAIT cell behaviour, for example, by enhancing or suppressing immune responses to achieve beneficial clinical outcome." Article: Drugs and drug-like molecules can modulate the function of mucosal-associated invariant T cells, Andrew N Keller, Sidonia B G Eckle, Weijun Xu, Ligong Liu, Victoria A Hughes, Jeffrey Y W Mak, Bronwyn S Meehan, Troi Pediongco, Richard W Birkinshaw, Zhenjun Chen, Huimeng Wang, Criselle D'Souza, Lars Kjer-Nielsen, Nicholas A Gherardin, Dale I Godfrey, Lyudmila Kostenko, Alexandra J Corbett, Anthony W Purcell, David P Fairlie, James McCluskey & Jamie Rossjohn, Nature Immunology, doi:10.1038/ni.3679, published online 6 February 2017.
Kassahn K.S.,Institute for Molecular Bioscience |
Waddell N.,Institute for Molecular Bioscience |
Grimmond S.M.,Institute for Molecular Bioscience
Integrative Biology | Year: 2011
The development of next-generation sequencing technologies has enabled the transcriptome to be measured and characterized at a level which was previously unattainable. Shot gun sequencing of RNAs, or RNA-Seq as it is known, is providing the means to simultaneously survey locus activity, transcript-specific expression, sequence content of transcripts and transcriptome discovery. This article discusses the current state of RNA-Seq, its potential for redefining transcriptomics and some of the challenges associated with this revolutionary technology. © The Royal Society of Chemistry 2011.
Achard M.E.S.,University of Queensland |
Chen K.W.,University of Queensland |
Sweet M.J.,Institute for Molecular Bioscience |
Watts R.E.,University of Queensland |
And 3 more authors.
Biochemical Journal | Year: 2013
Iron acquisition is an important aspect of the host-pathogen interaction. In the case of Salmonella it is established that catecholate siderophores are important for full virulence. In view of their very high affinity for ferric iron, functional studies of siderophores have been almost exclusively focused on their role in acquisition of iron from the host. In the present study, we investigated whether the siderophores (enterobactin and salmochelin) produced by Salmonella enterica sv. Typhimurium could act as antioxidants and protect from the oxidative stress encountered after macrophage invasion. Our results show that the ability to produce siderophores enhanced the survival of Salmonella in the macrophage mainly at the early stages of infection, coincident with the oxidative burst. Using siderophore biosynthetic and siderophore receptor mutants we demonstrated that salmochelin and enterobactin protect S. Typhimurium against ROS (reactive oxygen species) in vitro and that siderophores must be intracellular to confer full protection. We also investigated whether other chemically distinct siderophores (yersiniabactin and aerobactin) or the monomeric catechol 2,3-dihydroxy-benzoate could provide protection against oxidative stress and found that only catecholate siderophores have this property. Collectively, the results of the present study identify additional functions for siderophores during host-pathogen interactions. © 2013 Biochemical Society.
Loo D.,University of Queensland |
Loo D.,Institute for Molecular Bioscience |
Jones A.,Institute for Molecular Bioscience |
Hill M.M.,University of Queensland |
Hill M.M.,Institute for Molecular Bioscience
Journal of Proteome Research | Year: 2010
Alterations in protein glycosylation play an important role in patho-physiology, and much effort has been devoted to detecting glycoprotein biomarkers. In this manuscript, we describe the development of a novel method for monitoring alterations in protein glycosylation. Lectins are used as individual affinity reagents and coupled to magnetic beads (Dynabeads) in a microplate array format for isolation of glycosylated proteins. Isolated glycoproteins are digested with trypsin in-solution followed by LC-MS/MS, allowing a liquid handler-assisted high throughput workflow. We demonstrate the specific and reproducible affinity-isolation of glycoproteins using the lectin Dynabead array technology. When used with serum, we achieved one-step purification of glycoproteins with minimal coisolation of abundant serum proteins including albumin. We further optimized the proteomics workflow to allow transfer to a liquid handler for automation. In summary, we report the development of a high throughput platform to detect alterations in protein glycosylation which will be useful in glycoproteomics studies, particularly clinical proteomics studies where large sample sizes are required to achieve statistical power. © 2010 American Chemical Society.
News Article | March 10, 2016
A new study based on new modeling has shown that the average global temperature could rise by 1.5 degrees as early as 2020. According to a new study published by researchers from the University of Queensland and Griffith University in Australia, global warming could occur much more quickly than previously thought. The study is based on a new first-of-its-kind model which includes “energy use per person” as a predictive factor, rather than solely on economics or populations. The model forecasts that population and economic growth, combined with rising energy use per person could dramatically impact global energy demand, and subsequently CO2 emissions, making for an increase in the global average temperature by 1.5 degrees as early as 2020. “Nations at the 2015 UN Conference on Climate Change agreed to keep the rise in global average temperature below 2 degrees Celsius, preferably limiting it to 1.5 degrees to protect island states,” said Professor Hankamer, who along with Dr Liam Wagner developed the model. “Our model shows we may have less time left than expected to prevent world temperature from rising above these thresholds.” “World population is forecast to increase to over 9 billion people by 2050, which, together with international ‘pro-growth’ strategies, will lead to continually increasing energy demand.” As a result, according to Professor Hankamer, the global energy sector must transition away from fossil fuel-based energy sources towards renewable energy sources in an attempt to control global temperature averages. “The sun is by far the largest renewable energy source,” said Hankamer, a professor from the University of Queensland’s Institute for Molecular Bioscience. “In just two hours it delivers enough solar energy to the Earth’s surface to power the entire global economy for a year – and now is the time to make the switch.” Hankamer also believes there currently exists a quick first step to bolster such a transition. “A cost-neutral strategy that governments should consider to fast track this transition is diverting the $500 billion used to subsidise the fossil fuel industry internationally to assist the global renewable sector.” “We have a choice: leave people in poverty and speed towards dangerous global warming through the increased use of fossil fuels, or transition rapidly to renewables,” added Dr Liam Wagner, who partnered with Professor Hankamer in developing the model. “As 80 per cent of world energy is used as fuels and only 20 per cent as electricity, renewable fuels in particular will be critical.” Get CleanTechnica’s 1st (completely free) electric car report → “Electric Cars: What Early Adopters & First Followers Want.” Come attend CleanTechnica’s 1st “Cleantech Revolution Tour” event → in Berlin, Germany, April 9–10. Keep up to date with all the hottest cleantech news by subscribing to our (free) cleantech newsletter, or keep an eye on sector-specific news by getting our (also free) solar energy newsletter, electric vehicle newsletter, or wind energy newsletter.
News Article | January 20, 2016
While the phenomenon sounds like the stuff of horror films, it is common practice for these "butterflies of the ocean", a new University of Queensland-led study published today in PLOS One has found. Dr Karen Cheney of UQ's School of Biological Sciences said the multi-disciplinary study examined five closely-related nudibranchs (sea slugs) collected from the Great Barrier Reef and from South East Queensland, Australia. "These carnivorous creatures are well-known to scuba divers for their beautiful colours and intricate patterns," she said. "Science has known that many sea slugs obtain toxins from what they are eating, such as sponges, but in our study we found they selected only one toxin to store a particularly toxic compound called Latrunculin A. "Toxicity tests demonstrated that even the smallest amounts of the compound killed brine shrimp." "Further tests conducted at the Institute for Molecular Bioscience demonstrated that this compound was more toxic to cancer cell lines than other compounds found in sea slugs." Dr Cheney said sea slugs used chemical defences and bright colours to warn potential predators away, similar to poison dart frogs and brightly coloured butterflies which signalled they were toxic by their colours. "However, we still are learning if colour patterns are related to the strength of their chemical defences," she said. "We are investigating whether the most brightly coloured sea slugs are the most toxic, and also whether cryptic sea slugs that blend in with their environment also contain strong toxic defences." She said while fish recognised visual signals such as bright colours, the presence of the same toxic compound in the closely related sea slugs suggested that something else was at play. It was possible that other predators, such as crabs, might use other ways of detecting the toxicity of their prey. One future research avenue would be to explore how these creatures were able to eat their prey and transport toxic chemicals without causing internal damage. The study tapped into the expertise of co-author Professor Mary Garson of UQ's School of Chemistry and Molecular Biosciences, who has been researching chemicals stored by marine animals for the past 20 years. "One interesting study aspect is the potency of the compound which five different sea slug species chose to store," Professor Garson said. "This is a well-studied compound which kills cells. In this study we've uncovered a new use for it in an ecological context." Natural products play an invaluable role as a starting point in the drug discovery process. "The role this chosen toxin plays in the natural environment potentially could be transferred in the medical field to guide research into treatments for cancer research or neurodegenerative disease," Professor Garson said. Professor Garson said a good analogy for sea slugs, because of their bright colours, was the "butterflies of the ocean". Explore further: Traumatic mating may offer fitness benefits for female sea slugs
News Article | February 22, 2017
Researchers from The University of Queensland’s Institute for Molecular Bioscience (IMB) have developed a faster and more accurate method for assembling genomes which could help clinicians rapidly identify antibiotic-resistant infections. IMB Centre for Superbug Solutions Deputy Director Associate Professor Lachlan Coin says arming clinicians with this information could help them prescribe the most effective antibiotic for their patient. “Antibiotic resistance is a global challenge that threatens our ability to treat common infections,” he says. “Sequencing a bacterial genome using standard techniques resulted in a genome splitting into hundreds of fragments which was impossible to piece together. “In particular, pathogenicity islands — which are crucial to identifying antibiotic resistance — usually split across multiple pieces. “For the past two years, we have used cutting-edge Oxford Nanopore Technologies sequencing devices to sequence bacterial genomes and understand how antibiotic resistance develops. “Because this technology is so new, we needed to develop a powerful method that could help us make the most of its results and really understand the genetic drivers of antibiotic resistance,” Coin says. IMB Postdoctoral Researcher Dr. Minh Duc Cao says the team developed a new method for analysis of sequencing data on the fly, which allowed them to quickly and accurately piece together complete genomes. “With our method, we can reconstruct an entire bacterial genome shortly after you switch on the machine and put in the DNA sample. “The speed is key as we’re interested in predicting antibiotic resistance in real time on clinical samples, because when it comes to diagnosing and treating infections, every minute counts,” he says. Coin says the method could be applied to help unravel the genomic causes of other diseases. “We would like to work towards finding new ways to apply this approach to help unravel other diseases, particularly cancer. “Cancer genomes are about 1000 times larger than bacterial genomes, so the powerful combination of this leading technology and our improved method holds enormous potential for rapid assembly of personalized tumor genomes,” Coin says. The research was published in Nature Communications and was funded by The University of Queensland, National Health and Medical Research Council, and the Australian Research Council.