From manipulating molecules and creating world-first approaches to drug development through to comprehensive psychological support programs for people with cancer, research at the Faculty of Science spans the gamut of interventions to improve our health and wellbeing.
University of Sydney science researchers are forging new paths in human health that are set to revolutionise the way we treat some conditions – and the people who live with them.
Faculty of Science Associate Dean (Research), Professor Kate Jolliffe, says:
“Scientific research is going to underpin the solutions to most, if not all, of the world's key challenges, including improving our understanding of diseases and disorders. We want to understand how things work. That's what makes us scientists. And we want to make a difference in the real world. But before we can do that, we have to understand the fundamentals.”
Fundamental research at the molecular level is the specialty of Richard Payne, Professor of Organic Chemistry and Chemical Biology and Deputy Director of the ARC Centre of Excellence for Innovations in Peptide and Protein Science (CIPPS). His team is creating world-first approaches to drug development and the creation of safer clot-busting therapies.
Professor Payne says: “With natural biomolecules, such as blood clotting molecules made by blood feeders like ticks and mosquitoes, you can only get very small quantities from the natural source, but we've created a new and faster method for building bioactive proteins in the lab. We take natural molecules and create a supercharged synthetic version through a process known as post-translational modification that makes them more biologically active.”
These lab-created, nature-inspired molecules can be created from scratch and at scale, which could radically accelerate the overall drug discovery process.
Inspired by proteins naturally produced by ticks, the team is developing a world-first blood-thinner (anticoagulant) that doesn’t cause the bleeding side effects caused by other anticoagulants.
“This molecule could be used for a wide range of medical treatments, for example, as a clot-busting medicine, or as adjunct therapy for stroke. Now, we are in the process of licensing these technologies to a local biotechnology company with a view to future clinical trials,” says Professor Payne.
What’s really exciting is making fundamental discoveries that have translatable potential. We can now take natural peptides and proteins and supercharge them to improve their activity and develop new methods for drug synthesis.
One peptide, discovered by serendipity while working on cancer vaccines, is being commercialised via a University of Sydney spin-out company, Proteios.
“We noticed that a native human peptide we were using in the vaccines had immunosuppressive and anti-inflammatory qualities, so we focused on engineering this peptide to be more biologically active. Now, this peptide, called RP23, is being developed as a topical formulation for the treatment of skin diseases like psoriasis and eczema. We are now working to move the peptide toward clinical trials.”
Another key project is the development of a new anticoagulant that has its own built-in, fast-acting antidote.
Excessive bleeding is a critical concern when using blood-thinning drugs. But the on-demand reversible activity of the new peptide could revolutionise the use of anticoagulants, for example, in surgery where patients are at higher risk of bleeding.
This activation-deactivation mechanism is made possible by a relatively new focus of research for his lab, supramolecular chemistry, which uses non-covalent bonds such as the hydrogen bonds that help keep the double helix of DNA together. Supramolecular bonds are relatively weak and can be broken when needed.
“The result is a highly active drug that thins the blood when needed but can be switched off on demand,” says Professor Payne.
The supramolecular approach could lead to the development of a new generation of medicines and looks particularly promising in immunotherapy.
Professor Richard Payne with honours student Mel Shishido (left) and Dr Kat Harrison (standing) in the CIPPS labs in the School of Chemistry.
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LinkWe are in the process of licensing these technologies to a local biotechnology company with a view to future clinical trials.
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At the other end of the scientific research spectrum, Professor Haryana Dhillon, Senior Research Fellow at the School of Psychology, is finding effective ways to improve the emotional support and psychosocial care of people affected by cancer.
“A diagnosis of any condition can affect self-confidence, self-perception, or the ability to work, either due to the disease itself or as a consequence of treatment,” says Professor Dhillon, chair of the University’s Psycho-Oncology Cooperative Research Group (PoCoG).
“Our goal is to ensure that people live with the best quality of life, the lowest level of distress, and the greatest functional ability that they can achieve.”
As a recognised leader in psycho-oncology and through her clinical trials, Professor Dhillon has achieved significant gains for patients and has impacted current practice with a range of research projects.
We are producing outcomes that have an impact on practice and how healthcare is delivered to the world.
One of these projects is the international CHALLENGE (Colon Health And Life Long Exercise Change) trial, which examined the link between physical activity and disease-free survival in people treated for colon cancer who are at high risk of it recurring. These people have an increased risk of cardiovascular disease, type 2 diabetes, metabolic syndrome and osteoporosis, all of which can be reduced by physical exercise.
The ground-breaking study found a 37% lower risk of death and a 28% lower risk of new or recurrent cancer in patients who began a structured exercise program supported by an accredited exercise physiologist or health coach compared with patients who received health advice on its own.
These results put exercise on a par with, or superior to, many drug treatments – with only minor musculoskeletal side effects.
“Although there is clear observational data, there have been few high-quality studies designed to prospectively assess disease-free survival, making it difficult to develop evidence-based guidelines,” says Professor Dhillon.
These world-first findings are likely to change current practice to include exercise guidance following cancer treatment and are likely to influence upcoming cancer management guidelines.
Structured exercise programs have been shown to lower risk of death and new or recurrent cancer in recovering patients.
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LinkThe ongoing trial OXTOX aims to reduce the adverse effects of the chemotherapy drug oxaliplatin, which can result in peripheral neuropathy, causing tingling, numbness and pain in the hands and feet.
Professor Dhillon says: “There are many thousands of people treated for colorectal cancer with this particular drug, but because the toxicity from the chemotherapy is cumulative, it limits the amount of drug that people can tolerate.
“Our study is examining whether the drug ibudilast can decrease severity of acute neurotoxicity and peripheral neuropathy severity and help people to receive more oxaliplatin before needing to modify their chemotherapy. This is an old drug and it’s not expensive, so we’re trying to repurpose it to help people stay on the treatment they need.”
Animal studies completed by colleagues in the School of Psychology have proven promising and this current human study is based on this data.
Cognitive impairment caused by cancer and cancer treatments is often ignored compared to physical symptoms, yet it’s an important factor in quality of life.
Our researchers trialled a cognitive training program and found that it significantly improved people’s perception of their cognition, whether they objectively improved or not.
“Participants felt that their cognition improved, and they were less distressed as a result, so this was an important finding,” says Professor Dhillon.
The study contributed to changes in the American Society for Clinical Oncology's breast cancer survivorship guidelines, which recommends that patients be assessed for cognitive function and offered training if they have impairments.
Professor Haryana Dhillon (right) conducting neuropsychological assessment with patient.
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LinkProfessor Dhillon says: “At least 60% of people have some level of fear of recurrence and in 20% it is severe. We developed a five-session, psychologist-delivered intervention and found it produced a significant reduction in the level of fear.”
The group is developing ways to deliver the intervention that could be self-guided, such as booklets, telehealth or online, and is testing an adapted version for caregivers.
With such a broad spectrum of projects under way in the Faculty, Professor Jolliffe says: “Our overarching goal is to be the place where scientists carry out the best foundational, translational and transformational scientific research in Australia – and that puts us among the best in the world. We are ranked in the top 100 science faculties globally.”
