Dr Charles Cox with a microscope

Dr Charles Cox

Q and A with Dr Charles Cox

18 August 2023

Dr Charles Cox’s discovery that furthers our understanding of PIEZO ion channels set the science world alight. Here Dr Cox provides more insight into his research published in Science and the next steps to developing new therapeutics to target a whole range of diseases.

Did you name the molecule you discovered?

The molecule we identified that binds to PIEZO channels is a protein that was already discovered in 2000, although little research has been done on it. The protein that we identified in this research that is a regulator of PIEZO channels is called MDFIC and has probably most notably been shown to cause severe lymphatic malformations in humans.  

Could you explain us what PIEZO ion channels are?

PIEZO channels are cellular sensors of mechanical forces – they convert mechanical forces into electrical signals. Discovered in 2010 their discovery attracted the Nobel Prize in 2021 for their discoverer Dr Ardem Patapoutian. They have a huge number of roles in health and disease. For example, PIEZO2 is present in nerves in the skin that allow us to sense light touch.

How does this molecule interact with our brain?

This protein MDFIC influences PIEZO channels. It is the PIEZO channels that can in turn change the nerve signals sent to the brain.

How could the molecule help target osteoporosis and obesity? What would be the mechanism? 

In both of these cases, it would involve boosting the activity of PIEZO channels. For example, PIEZO1 channels influence bone density, we hope that in the future by boosting PIEZO1, through this protein that we identified can regulate PIEZO1, we can increase bone density and treat osteoporosis. For obesity, there are multiple potential mechanisms one is through boosting PIEZO2 activity in the stomach which could trick the brain into thinking the stomach is full.

Would it also help those with inflammatory diseases and cardiovascular diseases?

PIEZO1 is important in several inflammatory processes. Reducing PIEZO1 activity could reduce inflammation in some cases such as in joints. The protein we discovered that regulates PIEZO1 could be developed to boost or repress PIEZO1 channel activity which is why we think it could be used to develop several therapies for different diseases.

Could you tell us how a cryo-electron microscopy works and how you used it for your work?

This is a type of high-powered microscopy technique that can be used to determine the structure of proteins at exceptionally high resolution. Our collaborators used this technique to understand at the atomic level how these MDFIC proteins interact with PIEZO channels. This provides fundamental and essential information required to design the peptide-based therapeutics we discussed above.

What are the next steps before using this molecule in a clinical level with patients?

Of course, therapeutic applications in humans are a way off into the future. This basic discovery needs a lot of work to progress to the human level. We are currently optimising the portion of the protein that interacts with PIEZO channels that we hope will be able to be used therapeutically. Once we have a small potent peptide we can begin further testing in cells.

Acknowledgement of Country

The Victor Chang Cardiac Research Institute acknowledges Traditional Owners of Country throughout Australia and recognises the continuing connection to lands, waters and communities. We pay our respect to Aboriginal and Torres Strait Islander cultures; and to Elders past and present.

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