Established in 2020 Wednesday, October 27, 2021


Australian team gets to the heart of COVID-19
Professor David James. Sydney’s mass spectrometry capabilities advance COVID-19 trials. Image courtesy: The University of Sydney.



SYDNEY.- A collaboration between Professor David James from the University of Sydney and Associate Professor James Hudson from QIMR Berghofer, the project tackled one of the major complications of COVID-19 – the “cytokine storm.” This occurs when the immune system overreacts to the infection, releasing inflammatory molecules called ‘cytokines’ into the bloodstream.

“Certain individuals that are infected with COVID-19 generate this hyperimmune response, called the ‘cytokine storm’ that seemed to trigger organ damage, particularly in the heart,” said Professor David James, ARC Laureate and Leonard P. Ullmann Chair of Metabolic Systems Biology at the Charles Perkins Centre and the University’s Faculty of Medicine and Health and Faculty of Science.

“Our goal was to mimic this cytokine storm in a test tube to discover what was happening at the cellular level.”

“We wanted to find out exactly how the cytokine storm causes cardiac damage by identifying the proteins responsible then trying to repurpose existing drugs that target those proteins,” said Associate Professor Hudson, head of QIMR Berghofer’s Cardiac Bioengineering Research Group and senior author on the study.

“We thought understanding the biological basis of the heart damage was critical for identifying dugs with a much higher chance of success.”

The research was recently published in the prestigious journal Cell.

Applying world-leading phosphoproteomics
“At the University of Sydney we have, over a number of years, pioneered a technology based around mass spectrometry known as phosphoproteomics. It’s a very sensitive tool that in essence allows us to peel back a cell, peek inside and figure out exactly what is happening in that cell right now,” explains Professor James.

The Sydney Mass Spectrometry is part of the University’s core research facilities and is based at the Charles Perkins Centre.

The methods, spearheaded by co-author and mass spectrometrist Dr Sean Humphrey, have been used previously to examine what happens during exercise in skeletal muscle or with insulin in adipose cells, yielding major new insights into these processes.




“Our technology allows us to identify and quantify tens of thousands of changes in cells or tissues and from minute starting materials. Because we already have these methods established at the University of Sydney, we were able to rapidly apply them to this collaborative work on COVID-19,” said Dr Humphrey, Postdoctoral Research Fellow at the University’s School of Life and Environmental Sciences in the Faculty of Science.

"To see this kind of collaboration and research outcomes all come together in just 10 months is quite extraordinary." -Professor David James

The QIMR group members, led by Associate Professor James Hudson, are world leaders in developing lab-grown, stem-cell-derived miniature human heart organoids – a ‘heart-in-a-dish’, which were used in the study to explore what happens inside the heart cell when it is exposed to the cytokine storm.

“In particular we were interested in looking for things that happened inside the heart that we could drug and block,” said Professor James.

“We found that a protein called bromodomain protein 4 was markedly changed in the organoid hearts exposed to the cytokine storm and there were already a number of drugs available that targeted this but for other applications in cardiovascular disease. No one had ever linked it to COVID-19.”

The researchers then used the mini heart organoids to screen the efficacy of several existing drugs that inhibit this protein and found they could prevent and reverse the damage.

The final step
Based on these findings, and with urgency top of mind, the QIMR team modelled the impact of the COVID-induced cytokine storm in mice by inducing sepsis to test the efficacy of a drug currently in Phase III clinical trials for cardiovascular disease.

“The drug that we predicted might have efficacy in COVID-19 completely blocked morbidity associated with sepsis in mice,” said Professor James.

“The study started with a simple phone call, but with the cardiovascular outcomes we were seeing with COVID the research was conducted with true urgency. To see this kind of collaboration and research outcomes all come together in just 10 months is quite extraordinary.”

Canadian company Resverlogix has used the research findings as the basis for expanding its clinical trials in COVID-19 patients.







Today's News

March 28, 2021

Postcard from the edge... of a supermassive black hole

Does selfishness evolve? Ask a cannibal

Wisdom, loneliness and your intestinal multitude

Australian team gets to the heart of COVID-19

Control system helps several drones team up to deliver heavy packages

Iceland's volcanic eruption could be a long hauler

Fast-acting, color-changing molecular probe senses when a material is about to fail

Weaker antibody response to first COVID-19 vaccine dose found in long-term care residents

Laser-driven experiments provide insights into the formation of the universe

Leveraging the 5G network to wirelessly power IoT devices

Africa's Covid 2nd wave was worse but saw fewer measures

Study finds evidence of Bartonella infection in schizophrenia patients

Therapeutic bed can help keep preterm newborns' brain oxygen levels stable

Repurposed heart and flu drugs may help body fight sepsis

Carrying naloxone can save lives but newly abstinent opioid users resist

Team studies new use for pulmonary hypertension drug



 


Editor & Publisher: Jose Villarreal
Art Director: Juan José Sepúlveda Ramírez



Tell a Friend
Dear User, please complete the form below in order to recommend the ResearchNews newsletter to someone you know.
Please complete all fields marked *.
Sending Mail
Sending Successful