Study opens new drug therapy targets in a range of diseases

July 31, 2017

Scientists have a better understanding of the immune system at a molecular level, thanks to University of Queensland-led research that may now lead to a range of new treatments for disease.

The research provides a new foundation for therapeutic strategies against a wide range of diseases and infections, said Professor Bostjan Kobe.

"This study shows for the first time that signalling happens downstream of 'toll-like receptors' - proteins that play a key role in the innate immune system," Professor Kobe said.

"These receptors are a double-edged sword.

"On one hand, they protect us against infection, but they are also responsible for pathological inflammatory responses in a range of disorders from chronic inflammatory, autoimmune, cardiovascular and cancer-related disorders to pathologies associated with infections."

"For this reason, the associated pathways are important drug targets for a range of diseases."

Professor Kobe, of the School of Chemistry and Molecular Biosciences and the Australian Infectious Diseases Research Centre, said the signalling assemblies' structure provided the means to design therapeutic drugs using rational, structure-based approaches.

"These are similar to approaches Australian researchers used to develop the anti-flu drug Relenza," he said.

Innate immune receptors, particularly toll-like receptors, were discovered only in recent years, Professor Kobe said, with the 2011 Nobel Prize in Physiology or Medicine co-awarded to Bruce Beutler and Jules Hoffmann for their discovery.

"The mechanism of signalling has been a matter of controversy," Professor Kobe said.

"Many incorrect molecular models were proposed over last 15 years, but the data they were based on was too limited."

"We managed to reconstitute the signalling assembly, determine its structure by using cryo-electron microscopy, and provide conclusive evidence that explains signalling in the cell.

"This is a rather novel type of signalling we have called SCAF (Signalling by Cooperative Assembly Formation).

"A large assembly forms very quickly after minimal stimulus, achieving very high amplification very rapidly. This is exactly what's needed in the first stage of immune response."

In a report published in the journal Nature Structural and Molecular Biology (DOI 10.1038/nsmb.3444), the international research team described how the signal is amplified after the membrane receptor senses a pathogen and initiates an inflammatory response.
-end-
A National Health and Medical Research Council project grant funded the study.

The international collaborators included the teams of Dr Thomas Ve who started work in Professor Kobe's lab at UQ and recently moved to Griffith University, Dr Kate Stacey, Dr Michael Landsberg and Dr Mehdi Mobli at UQ, Dr Yann Gambin and Dr Emma Sierecki at the University of New South Wales, and Professor Ed Egelman at the University of Virginia, USA.

University of Queensland

Related Immune System Articles from Brightsurf:

How the immune system remembers viruses
For a person to acquire immunity to a disease, T cells must develop into memory cells after contact with the pathogen.

How does the immune system develop in the first days of life?
Researchers highlight the anti-inflammatory response taking place after birth and designed to shield the newborn from infection.

Memory training for the immune system
The immune system will memorize the pathogen after an infection and can therefore react promptly after reinfection with the same pathogen.

Immune system may have another job -- combatting depression
An inflammatory autoimmune response within the central nervous system similar to one linked to neurodegenerative diseases such as multiple sclerosis (MS) has also been found in the spinal fluid of healthy people, according to a new Yale-led study comparing immune system cells in the spinal fluid of MS patients and healthy subjects.

COVID-19: Immune system derails
Contrary to what has been generally assumed so far, a severe course of COVID-19 does not solely result in a strong immune reaction - rather, the immune response is caught in a continuous loop of activation and inhibition.

Immune cell steroids help tumours suppress the immune system, offering new drug targets
Tumours found to evade the immune system by telling immune cells to produce immunosuppressive steroids.

Immune system -- Knocked off balance
Instead of protecting us, the immune system can sometimes go awry, as in the case of autoimmune diseases and allergies.

Too much salt weakens the immune system
A high-salt diet is not only bad for one's blood pressure, but also for the immune system.

Parkinson's and the immune system
Mutations in the Parkin gene are a common cause of hereditary forms of Parkinson's disease.

How an immune system regulator shifts the balance of immune cells
Researchers have provided new insight on the role of cyclic AMP (cAMP) in regulating the immune response.

Read More: Immune System News and Immune System Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.