Drug goal pathway may unlock therapies for diabetes, most cancers and COVID – UQ Information

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Scientists have visualized and investigated an important molecular pathway that could one day help treat inflammation, diabetes, cancer, infectious diseases, and possibly even COVID-19.

The international collaboration with researchers from the University of Queensland isolated and examined the MyD88 molecule and found the missing link between immune cell receptors and the body’s inflammatory response.

UQ’s Professor Bostjan Kobe said that a few years ago he and his colleagues identified a gap in our understanding of how inflammation is activated in the body.

“Our immune system triggers inflammation as a protective measure when pathogens or bacteria enter our body. Sometimes, however, this defense goes wrong and can make our body’s handling of the disease worse,” said Professor Kobe

“We knew that signals sent by the receptors on the surface of immune cells lead to inflammation in the body, but we didn’t understand how this happens at the molecular level.

“Now we’ve studied and visualized an incredibly important protein called MyD88.

“This is an important signaling molecule in immune pathways. Its job is to relay a message from the immune cell receptors to the body in order to trigger an immune response.

“While immunity is clearly required to fight pathogens, the immune system can sometimes falsely trigger an inflammatory response or overactivate it even after the pathogen is gone.”

By better understanding how this pathway can be blocked, researchers could treat diseases like rheumatoid arthritis, diabetes, cancer, and even COVID-19.

Dr. Griffith University’s Thomas Ve said the research was accomplished thanks to advances in molecular visualization and analysis technology.

“Just a few years ago, ‘conventional’ techniques like X-ray crystallography could not study these types of proteins,” said Dr. Ve.

“We had to develop and deploy some cutting-edge technologies, in this case micro-crystal electron diffraction and X-ray-free electron lasers.

“This is one of the first times that microcrystalline electron diffraction has been used to identify a new protein structure in this way.

“And this was one of the first comparisons of these new structural biology techniques.

“Ultimately, these two incredible technologies gave us the world’s first clear picture of this critical inflammation target.”

The research was published in Nature Communications (DOI: 10.1038 / s41467-021-22590-6).

The collaborative study was carried out by the research groups of Professor Bostjan Kobe, Dr. Thomas Ve, Dr. Hongyi Xu (Stockholm University) and Dr. Connie Darmanin (University of La Trobe).

Research grants were received from the Australian Research Council, the National Health and Medical Research Council, the Swedish Research Council, the Knut and Alice Wallenberg Foundation, and the SciLifeLab technology development project.

Media: Professor Bostjan Kobe, b.kobe@uq.edu.au, +61 407 009 170; Dominic Jarvis, dominic.jarvis@uq.edu.au+61 413 334 924; Deborah Marshall, d.marshall@griffith.edu.au, +61 7 3735 5245.