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Centenary Institute - Medical Research
Centenary Institute - Medical Research

Pathway to eliminating antibiotic-resistant tuberculosis in the Pacific

Australian researchers, including from the Centenary Institute have been awarded funding for a major project that aims to eliminate both active and latent tuberculosis (TB) found on Kiribati, an island nation in the central Pacific Ocean. The project will also support multidrug-resistant TB control education and management through the Pacific region.

Led by Professor Barend Marais of the University of Sydney, Professor Warwick Britton AO, Head of the Centenary Institute’s Tuberculosis Research Program will be a Chief Investigator (CIB) on the project with colleagues from the NHMRC Centre of Research Excellence in Tuberculosis Control.

“A TB hotspot, Kiribati has extremely high rates of tuberculosis. The capital Tarawa, one of the most densely populated areas in the Pacific, has a TB incidence rate among the highest in the world,” said Professor Britton.

“Our project will ensure that every person over the age of 2 will be screened for TB disease or infection in Tarawa with appropriate treatment strategies then implemented. Our integrated project will also provide a pathway towards drug resistant TB prevention and TB elimination  more broadly within the Pacific, through a program of training and mentoring.”

“Overall, this program will be a catalyst in regional TB elimination efforts, helping save lives and overcoming a disease which has devastating impact on communities,” he said.

The Federal Government’s announcement regarding the project funding can be accessed online.

TB is a leading cause of death globally responsible for approximately 1.5 million deaths annually.

Read more about Professor Britton and his research here.

Image Credit: Vladimir Lysenko. https://commons.wikimedia.org/w/index.php?curid=39278217

Biomarker signature found for TB infection

A group of leading Australian researchers have uncovered a unique blood-based biomarker signature in individuals infected by tuberculosis (TB).

The presence of the biomarker signature, found through a simple blood test, allows individuals with infectious TB–including those with non-symptomatic early-stage disease–to be easily identified and treated.

The finding, reported in the Journal of Infection, could be key in supporting health efforts to control and eventually eliminate the TB epidemic which is responsible for approximately 1.5 million deaths each year globally.

“A major issue in controlling the spread of tuberculosis is the difficulty of detecting the disease quickly and effectively, particularly in developing countries and in remote areas where technology and testing facilities may be limited,” says lead author of the study, Dr Jennifer Ho from the Centenary Institute and the Woolcock Institute of Medical Research

“Sputum smear microscopy is the test used to diagnose TB in the majority of endemic settings but it is unable to pick-up TB in its early stages which prevents timely diagnosis and treatment.”

“Also problematical are individuals with latent TB who possess no physical sickness or symptoms,” she says. “Unaware they are infected, these individuals can become TB spreaders if their disease progresses at some point to an active state.”

Dr Ho notes that it is estimated that over 3.3 million cases of active TB are undetected annually, contributing to the uncontrolled spread of TB.

“Our biomarker discovery could be used as the basis for a highly effective and simple diagnostic blood test to help detect these prevalent cases of TB in the community,” she says.

Professor Warwick Britton, Head of the Centenary Institute’s Tuberculosis Research

Program and senior researcher on the project says that active TB case finding, including systematic screening of high risk groups, will be required to dramatically reduce TB incidence worldwide.

“Early case detection and appropriate treatment is absolutely critical to getting on top of this highly infectious disease,” he says. “Our research offers up an exciting new approach to help realise the ambition of global TB elimination.”

The research was a collaboration between scientists at the Centenary Institute, the Woolcock Institute of Medical Research, University of Sydney, UNSW Sydney and University of Technology Sydney.

Read the full media release here.

Centenary Institute’s rising stars

The Centenary Institute’s Dr Stefan Oehlers (Immune-vascular Interactions Laboratory within the Tuberculosis Research Program), Dr Jessamy Tiffen (Melanoma Oncology and Immunology Program) and Dr Hui Emma Zhang (Liver Enzymes in Metabolism and Inflammation Program) have all been named on the Educator’s list of Higher Education Rising Stars for 2020.

The list showcases individuals across the higher education spectrum who are making waves in the early stages of their careers and who have demonstrated leadership, innovation and achievement in their career to date.

Read more by clicking the link here:

Influenza susceptibility linked to variable responses to interferons in the lung

Researchers at the Centenary Institute and the University of Sydney have discovered a key reason as to why the influenza virus is so effective at establishing infection and causing damage in the lungs.

They found that a group of lung-cells, following influenza infection, responded only poorly to interferons (the signalling proteins that help defend the body against viral attack). The research could pave the way for the development of new and improved anti-influenza drugs and vaccines, to both improve health and to save lives.

“Interferons are critically essential to our defence against pathogens including the influenza virus,” said Associate Professor Carl Feng (pictured), senior study author from the Centenary Institute and the University of Sydney. “The proteins are so named because they ‘interfere’ with the ability of viruses to multiply in the body.”

“It’s been known for a long time that during influenza, lung cells and immune cells in the lungs secrete interferons causing virus-infected cells to initiate anti-viral defences,” said Associate Professor Feng.

“However, how interferons actually undertake this protective activity is still not understood because the signalling proteins can act on hundreds of different types of cells in our body,” he said.

In their study, Associate Professor Feng and colleagues have generated a new tool to identify which cells respond to interferons in influenza infected mice. The goal was to work out whether the outcome of infection and interferon signalling differed between different cell types. What the researchers have demonstrated in the study is that not every cell type reacts equally to the interferons, even when they are in close proximity to each other.

“We were able to show that cells in influenza-infected mice reacted to interferons in dissimilar ways. Most notably, we found that one type of lung cell, the major target of the influenza virus, responded extremely poorly to interferons and were highly vulnerable to viral infection. This was particularly noticeable at the early-stage of the influenza infection cycle,” said Associate Professor Feng.

The research has the potential to lead to the development of new vaccination strategies and therapeutics that are more effective than the currently available anti-influenza drugs.

“Influenza remains among the most significant global infectious diseases owing to its high infectivity, the variable usefulness of current vaccines and the limitations of anti-viral therapy. It’s also a major health burden in Australia and globally,” said the Centenary Institute and University of Sydney’s Professor Warwick Britton, also an author of the study.

“A better understanding of how this virus infection is controlled by lung cells can help us to find medical solutions against influenza which results in millions of cases of severe illness and which is responsible for killing up to half a million people each and every year,” he says.

The investigators plan to study human lung-cells and their response to interferons and the influenza virus as a next-step of the research program.

Read the full media release here.

Read the publication in Cell Reports here.

Sea sponge could be key in fight against TB

An Australian sea sponge could hold the key to successfully combatting the deadly disease tuberculosis (TB), a new study from the Centenary Institute and the University of Sydney suggests.

Reported in the journal ‘Nature Scientific Reports’, the sea sponge was found to contain an exceptionally potent anti-bacterial agent able to inhibit Mycobacterium tuberculosis–the bacteria that causes TB in humans.

Every year more than 10 million people fall ill with TB and 1.8 million die from the disease. The new finding has the potential to open-up a new avenue of research to target what is the world’s top infectious disease killer.

“TB is a major global health problem and our battle against this resilient and deadly disease is incredibly difficult,” said the study’s lead author, Dr Diana Quan, a researcher affiliated with the Centenary Institute and the Microbial Pathogenesis and Immunity Group led by Professor Jamie Triccas at the University of Sydney.

“Effective antibiotics for TB are difficult to develop, there are constant issues with new drug-resistant TB strains and our current treatment approach for TB is both lengthy and complicated,” she said. “There is an urgent need for new drugs and antibiotics which can shorten and simplify TB treatment in order to combat this burgeoning TB pandemic.”

In the reported study, a sea sponge from the Tedaniidae family was examined by Dr Quan and found to yield compounds that displayed strong inhibitory potency against TB and also importantly, against drug-resistant strains of the disease. Following analysis, the active component from the sponge was identified as bengamide B which was also found to be non-toxic when tested against human cell lines.

“This is an extremely exciting finding,” said Dr Quan. “Bengamide B shows significant potential as a new class of compound for the treatment of tuberculosis and also importantly, for the treatment of drug-resistant TB which is an ever increasing obstacle to TB eradication around the world.”

The sea sponge was harvested off the Queensland coast and was one of approximately 1,500 different marine samples tested by Dr Quan for possible effectiveness against TB over the course of a three year program.

Read the full media release here.

ABC news interview with Dr Quan

Australian trial halves TB

Annual community-wide screening for tuberculosis almost halves the number of cases of the deadly disease, a four-year study by Australian and Vietnamese researchers has found.

Globally significant findings from the Woolcock Institute of Medical Research, in close collaboration with the Centenary Institute in Sydney and the National Lung Hospital in Vietnam, shows a pathway towards the eventual elimination of this global scourge.

The study, involving 100,000 people in Vietnam, found community-wide active case finding was 44 per cent more effective than standard passive case detection alone in reducing the prevalence of tuberculosis in the general population. Importantly, the active case finding intervention halved rates of TB infection among school-aged children.

“Our findings show that, with existing tests and treatments used in innovative ways, we can achieve the sort of impact on TB that makes it possible to consider the elimination of this dreadful disease,” says study leader, Woolcock epidemiologist and respiratory physician Professor Guy Marks. “Community-wide screening can interrupt the cycle of active disease and infection that perpetuates the deadly tuberculosis epidemic.“

Professor Warwick Britton, Centenary Institute’s Head of Tuberculosis Research Program said, “Tuberculosis takes a huge toll in human suffering and economic impact on communities worldwide. The important findings from this study demonstrate the effectiveness of a new approach to tuberculosis control. It highlights the value of collaboration between our Vietnamese colleagues and researchers in the Woolcock and Centenary Institutes.”

Read the full media release from the Woolcock Institute here: https://woolcock.org.au/news-4/australian-trial-halves-tb-study

The paper, ‘Community-wide Screening for Tuberculosis in a High-Prevalence Setting’, can be viewed online at the New England Journal of Medicine: https://www.nejm.org/doi/full/10.1056/NEJMoa1902129

‘The Wire’ radio interview: New tuberculosis vaccine in the works

Dr Anneliese Ashhurst from the Centenary Institute and the University of Sydney has talked about her exciting work on a new tuberculosis vaccine on the radio program ‘The Wire.

“Tuberculosis is a huge world-wide health problem. It’s caused by a bacteria that infects the lungs, is contagious and results in approximately 1.6 million deaths per year globally,” says Dr Ashhurst.

An early-stage synthetic vaccine which has been developed by Dr Ashhurst and a team of scientists has demonstrated its effectiveness in pre-clinical trials. Next steps will be to determine if the vaccine can be developed into a form suitable for use in humans.

Check out the interview here.

Exciting new vaccine targets killer disease TB

Australian medical researchers from the Centenary Institute and the University of Sydney have successfully developed and tested a new type of vaccine targeting tuberculosis (TB), the world’s top infectious disease killer.

Reported in the ‘Journal of Medicinal Chemistry’, the early-stage vaccine was shown to provide substantial protection against TB in a pre-clinical laboratory setting.

“Tuberculosis is a huge world-wide health problem. It’s caused by a bacteria that infects the lungs after it’s inhaled, is contagious and results in approximately 1.6 million deaths per year globally,” said Dr Anneliese Ashhurst, co-lead author of the reported study and affiliated with both the Centenary Institute and the University of Sydney.

The research program targeting the deadly disease has currently taken over five years of effort to implement. During that time Dr Ashhurst and a team of scientists have created the advanced synthetic TB vaccine and have now demonstrated its effectiveness using mouse models.

“Two peptides (small proteins) which are normally found in tuberculosis bacteria were synthesized and then bound extremely tightly to an adjuvant (a stimulant) that was able to kick-start the immune response in the lungs,” said Dr Ashhurst.

“We were then able to show that when this vaccine was inhaled into the lungs, it stimulated the type of T cells known to protect against TB. Importantly, we then demonstrated that this type of vaccine could successfully protect against experimental airborne TB infection,” she said.

Professor Warwick Britton, Head of the Centenary Institute Tuberculosis Research Program and co-senior researcher on the project with Professor Richard Payne, School of Chemistry, University of Sydney, emphasized the importance of the work being done.

“There currently exists only one lone vaccine for TB (known as BCG) and this is only effective in reducing the risk of disease for infants,” said Professor Britton.

“It fails to prevent infection or provide long term protection in older individuals and it isn’t considered suitable for use in individuals with an impaired immune system. More effective vaccines are urgently required to save lives,” he said.

Read the full media release here.

Tuberculosis and cancer discoveries vie for top award

Two Australian researchers have made revolutionary discoveries with the potential to offer exciting new approaches in the battle against disease – one targeting tuberculosis and the other cancer – and are now battling it out for top prize at the upcoming 2019 Centenary Institute Medical Innovation Awards.

The awards, which recognise and celebrate Australia’s inspiring young researchers who are successfully challenging the big questions of medical research, has a prize pool in excess of $50,000 on offer. The finalists and their ground-breaking discoveries have now been officially announced.

Dr Elinor Hortle* (pictured left) from the Centenary Institute has been selected for her discovery that platelets (cells that help the body form clots to stop bleeding) have an active role in the development of tuberculosis (TB). The major implication of her work is that anti-platelet drugs including aspirin may be an effective therapy for tuberculosis. With TB disproportionately affecting the developing world, the ability to extend current treatment regimens with such a cheap, safe, clinically approved drug could have an enormous impact on the global control of this deadly infectious disease.

Dr Simone Park* (pictured right) from the Peter Doherty Institute for Infection & Immunity at The University of Melbourne is the other finalist. Her research is focused on better understanding how the immune system can be targeted and/or activated to treat disease including cancer. She discovered that specialised immune cells – known as tissue-resident memory T (TRM) cells – could suppress the growth of melanoma cancer cells without completely eliminating them. In identifying that TRM cells are critical players in the anti-cancer immune response, she believes that the targeting of these cells could open the door to a new and innovative strategy to improve cancer treatments.

The two finalists were chosen from 32 entries submitted for the Centenary Institute Medical Innovation Awards, representing 22 research institutions and universities, across five Australian states.

“The selection of the two finalists was the result of careful consideration from a line-up of distinguished judges comprising some of the most prestigious scientists around the world,” said Centenary Institute Executive Director Professor Mathew Vadas.

“It is enormously exciting to see the quality of the applications for this award improve each year. Our future, as a high performing and innovative nation in medical research, is firmly linked to the long-term support of these wonderful talents,” he said.

The winner of the top award, the ‘In Memory of Neil Lawrence Prize’ will receive $30,000 from Commonwealth Private to support their research, as well as a perpetual Nick Mount hand blown glass trophy.

The runner-up will receive the ‘Bayer Innovation Award’ and $15,000 to continue to develop their research. One of these two award winners will also be presented the ‘Harvard Club of Australia Foundation Travel Prize’ worth $5,000 for the purpose of travelling to Harvard University, Boston, Massachusetts, USA to explore opportunities for collaboration.

A ‘People’s Choice Award’, voted on by the general public and research community has taken place and was won by Dr Elise McGlashan from the Turner Institute for Brain and Mental Health – Monash University, for her work showing that simple changes to light exposure could dramatically increase the number of patients who benefit from first-line antidepressant medications.

All three award winning scientists will be recognised at the 2019 Centenary Institute Medical Innovation Awards announcement ceremony, taking place in Sydney on Wednesday 21st August, 2019.

About the CIMIA: The annual Centenary Institute Medical Innovation Awards are designed to recognise and celebrate Australia’s bold young researchers who are taking risks and challenging the big questions of medical research, while promoting a domestic culture of brilliance in medical research. The finalists are selected and ranked after careful consideration by an international panel of adjudicators.

* Presented in alphabetic order by surname

Read the full media release here.

Successful funding for Centenary researchers

Two Centenary Institute researchers have successfully received funding grants through the Perpetual 2019 IMPACT Philanthropy program.

Prof Warwick Britton, Head of the Centenary Tuberculosis Program received funding for his project ‘Visualising how the immune system controls infection and inflammation.’

By using new imaging techniques, he hopes to be able to visualise how the immune system provokes a chronic inflammatory response in infected tissues during TB and leprosy and during immunotherapy, which can cause damage to the lung.

“Both tuberculosis and leprosy are diseases caused by the person’s immediate system reacting to the causative mycobacteria, damaging the lungs and skin/nerves respectively. Understanding how the immune cells cause this damage will help us prevent the permanent damage from these diseases. The funding from Perpetual Trustees will help us to analyse the interaction between immune cells in biopsy samples from TB and leprosy patients. This will utilise newly developed techniques using multiple antibodies to label the different immune cells in biopsy samples. The studies will be done in collaboration with clinicians in Sydney, Sri Lanka and China,” explained Prof Britton.

Dr Hui Emma Zhang received funding for her project titled, ‘Targeting unique enzyme activities for a novel therapy for liver cancer.’

“This funding will greatly facilitate my research on liver cancer, which is the third leading cause of cancer-related deaths worldwide. This funding will help me set up mouse models that recapitulate human liver cancer and evaluate the potential therapeutic benefit of novel drugs that target proteases in the liver,” says Dr Zhang.

The Perpetual 2019 IMPACT Philanthropy program distributes more than $100m annually from charitable trusts and endowments.