Finding the key to metabolic health

The human body is flooded with a handy little enzyme called adenosine monophosphate-activated protein kinase (or AMPK for short), which acts as our cells’ fuel gauge.

It’s more than just a gauge though – when it senses an energy surplus, it tells a cell to store energy and create molecules like fat, while in a deficit it instructs cells to use their stores.

Although quite a lot is known about AMPK and its functions, in large part thanks to work done over decades at SVI, what is yet to be discovered is a precise method to either switch AMPK off or on in specific cells.

This is the goal of research in Associate Professor Jon Oakhill’s Metabolic Signalling Lab.

“We know that if you can turn AMPK on in certain cells, you can potentially treat conditions like type 2 diabetes, but equally, if you could switch it off in the brain you could stop the damage done by stroke,” he said.

“The problem is that AMPK is in every cell. For something like stroke, you only want AMPK to be turned off in very specific areas so that you don’t cause a cascade with off target effects.”

Jon’s research into potential drugs that can be used to turn the enzyme on or off has implications for a wide range of diseases, including cancer, liver disease, type 2 diabetes and neurodegeneration.

Capitalising on this, in 2023 Jon was awarded an NHMRC Synergy Grant as part of a collaboration with James Cook University in Queensland to find new treatments for aortic aneurysm, a deadly disorder that causes weakening of the main abdominal artery.

He also was recipient of a Heart Foundation Vanguard Grant, a Diabetes Australia Grant and an NHMRC Ideas Grant to test new avenues of treatment for heart disease, for diabetes and for non-alcoholic fatty liver disease.

“We are working closely with medicinal chemists to develop drugs that can specifically target AMPK in certain cell types to avoid the problems that occur if AMPK is turned on or off in every cell.”

As an internationally recognised expert on AMPK, Jon is building on the work of giants in the field like SVI’s Professor Bruce Kemp, who was the first in the world to sequence the enzyme.

“Bruce’s work broke new ground on our understanding of the role kinases like AMPK play within an individual cell. It is thanks to pioneers like him that we understand the potential of AMPK.”

“What we have to do now is unlock it.”

The Lions share

There are a surprising number of parallels between the Lions Clubs and SVI. Most importantly, both organisations are driven by a desire to improve humanity.

Coincidentally, the first Lions Club in Victoria was formed at the same time that SVI’s benefactor, Jack Holt, left a generous bequest of 200,000 pounds to establish the Institute.

Members of the Lions Club first visited SVI in 2022, on the urging of postdoctoral scientist Dr Martha Blank, who has been part of Lions since 2018.

Since that time the relationship has blossomed, resulting in a commitment from Lions to contribute towards a cutting-edge piece of equipment, important for Institute research into cancer, type 2 diabetes and osteoporosis.

Lions in Victoria have been at the forefront of significant projects, supporting many medical research projects in the State.  They are continuing this legacy with their support of SVI.

Associate Professor Jon Oakhill has enjoyed meeting with representatives of Lions from District 201V1-4 and is grateful for the support pledged by the Clubs in this District.

“Something that shines through the work of Lions, and which resonates with me, is the desire to make a difference.” says Jon.

“Success in medical research requires the input of many, from students at the coalface in the labs, through to philanthropists. Support from community organisations like Lions, by their willingness to invest in our purchase of cutting-edge equipment, is instrumental in helping us to transform lives through medical research.”