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Centenary Institute - Medical Research
Centenary Institute - Medical Research

New understanding of how proteins operate

A ground-breaking discovery by Centenary Institute scientists has provided new understanding as to the nature of proteins and how they exist and operate in the human body.

The key finding–the changing state of a protein’s structural bonds–is likely to have significant implications as to how proteins are targeted by medical researchers, particularly in terms of drug development and the fight against disease.

Proteins are responsible for all of life’s processes and had previously been considered to exist in an intact single state when mature. The new study however has found two human proteins involved in blood clotting and immunity existing in different and changing states.

“The most sophisticated molecules made in nature are proteins which consist of unique sequences of amino acids,” said Dr Diego Butera from the ACRF Centenary Cancer Research Centre and lead author of the study (pictured right). “Disulphide bonds link the amino acid chains together and were thought to just stabilise protein structure.”

Previously it has been believed that these disulphide bonds were fully formed in the mature and functional protein. In this study however, the researchers found that the proteins are being produced in multiple disulphide-bonded states.

“We were able to precisely measure whether the disulphide bonds in the blood proteins were formed or broken. Remarkably, we saw that the proteins were made in multiple, possibly thousands, of different disulphide-bonded states,” said Dr Butera.

Professor Philip Hogg, Head of the ACRF Centenary Cancer Research Centre and senior author of the study believes that their research will change how proteins are viewed and targeted in future drug and medical experiments.

“It’s very likely that we will find many other proteins that exist in multiple states. Crucially, a drug may bind more or less preferentially to different states, impacting the effectiveness of the drug.”

“In experimental settings, differing states of a protein should now be considered as part of the investigative medical research process,” Professor Hogg said.

The study was published in the prestigious science journal ‘Nature Communications’.

Publication: Fibrinogen function achieved through multiple covalent states.

Cardiovascular research excellence recognised

Four scientists from the Centenary Institute have had their world-leading research recognised by being awarded prestigious NSW Cardiovascular Research Capacity Building Grants. The grants will help drive the scientists work focused on improving the health of patients with heart and cardiovascular conditions.

“Cardiovascular disease is a leading cause of death and disability in Australia. We need to continue to accelerate our research efforts in this critical health area to develop new and innovative treatments and to improve the heart health of all Australians,” says Professor Mathew Vadas AO, Executive Director at the Centenary Institute.

“Accordingly, these grants are an excellent outcome, both for our scientists who are operating at the very forefront of their research fields, as well as for the wider community who will ultimately benefit from the life-changing medical research being undertaken,” he says.

Successful Centenary Institute scientists and their research are (pictured top left to right):

Professor Philip Hogg. Centenary Institute (ACRF Centenary Cancer Research Centre) and University of Sydney. Awarded a Cardiovascular Senior Researcher Grant. Redefining protein function in thrombosis: Implications for pro-thrombotic states and anti-thrombotic drug resistance in patients with cardiovascular disease.

Dr Paul Coleman. Centenary Institute (Vascular Biology Program), Heart Research Institute and University of Sydney. Awarded a Cardiovascular Early-Mid Career Researcher Grant. Redox control of VWF processing and activity during thrombotic diseases.

Dr Renjing Liu. Centenary Institute (Vascular Biology Program) and University of Sydney. Awarded a Cardiovascular Early-Mid Career Researcher Grant. Targeting Tet2 as a therapy for vascular calcification.

Dr Yanfei (Jacob) Qi. Centenary Institute (Vascular Biology Program) and University of Sydney. Awarded a Cardiovascular Early-Mid Career Researcher Grant. Targeting blood vessel cells to treat atherosclerosis.

The NSW Cardiovascular Disease Research Capacity Building Program and its grants are a NSW Government initiative aiming to drive discoveries that allow researchers to find ways to better diagnose, treat and prevent cardiovascular disease, improving the health and wellbeing of people living in NSW.

Read the full media release here.

Prime7 News – featuring Professor Philip Hogg

Professor Philip Hogg, Deputy Director at the Centenary Institute and Head of the ACRF Centenary Cancer Research Centre has been interviewed by Prime7 News on the launch of the ACRF Tumour Metabolism Laboratory – part of the ACRF Centenary Cancer Research Centre.

The laboratory, established by a $2.5M grant from the Australian Cancer Research Foundation to the Centenary Institute (together with additional support from the Cancer Institute NSW and the University of Sydney) is dedicated to the study of tumour cell metabolism, down to a molecular level. This knowledge is then utilised in the development of innovative new cancer diagnostics, treatments and cures.

Click here for the Prime7 news story about Professor Hogg and the laboratory’s exciting work on outsmarting cancer cells.