Breaking the link between fat and diabetes: 2009 Science Minister’s Prize for Life Scientist of the Year

Media releases, Prime Minister’s Prizes for Science, Prime Minister’s Prizes for Science 2009

MichaelCowley_IMG_3367Michael Cowley

Why do we get fat? What’s the link between obesity, diabetes and hypertension? Can we break the link? These are critical questions for Australia’s long-term health, and Michael Cowley may have the answers.

He’s shown how our brains manage our consumption and storage of fat and sugar and how that can go wrong. He’s created a biotech company that’s trialling four obesity treatments.

Michael has shown unequivocally that losing weight isn’t just a matter of will power.

Now with his colleagues at Monash University he is discovering why obesity increases risks of heart disease and diabetes. And he’s developing therapies to break the connection between these conditions.

For his contribution to our understanding of metabolism and obesity, Michael Cowley receives the 2009 Science Minister’s Prize for Life Scientist of the Year.
Michael Cowley’s passion for science was fired, he says, by the ABC’s Science Show. “It was the highlight of my week—every Saturday lunchtime I’d come in from the farm to listen to Robyn Williams.”

But at university he struggled with the maths required for physics, and turned instead to biology. Roger Short introduced him to endocrinology (the study of hormones) and encouraged him to travel to Africa to investigate a drug for population control in elephants.

Michael was hooked on turning ideas into action. He went on to complete a PhD studying how the brain controls reproduction.

In 1998 he moved to the United States and turned his skills to the complex issue of how our brains control metabolism.

“The average adult’s weight increases by less than 500 grams a year,” he says. “That’s the equivalent of just a few potato chips a day. Our bodies do a remarkable job of balancing our food intake and energy output.”

And yet nearly two and a half million Australians are obese, and most of us are overweight. That makes us much more at risk of diabetes and hypertension. What’s gone wrong?

“In evolutionary terms it’s good to put on weight,” says Michael. “Over the millennia our ancestors have needed reserves to survive famine.” Farming and city living have changed all that. Now we live mostly sedentary lives and we have all the high energy food we want. But our brains haven’t caught up with the change.

“There are good metabolic reasons why we struggle to lose weight. It’s not just about will power. For some of us, compulsive food consumption mirrors drug addiction.”

Working with mice and monkeys over the last ten years, Michael has managed to unravel some of the complexity of metabolism and obesity, and to discover potential targets for therapy.

In 1999 he started working at Oregon Health and Science University on understanding the action of the hormone leptin on the brain. A few years earlier researchers had discovered that leptin could regulate body weight. Michael identified the neurons in the brain that responded to leptin. He found that leptin activated neurons that suppress weight, and inhibited neurons that increase weight. He also showed how these two types of neurons act to increase or decrease weight.

Central to Michael’s work has been his development of a method to study the actions of hormones in individual living nerve cells within slices of brain tissue. This technique is now widely used across neuroscience. Combined with Michael’s studies of mice and monkeys, and clinical studies in humans, it has led him to a series of discoveries including:

  • how the brain determines when our stomach is full and what’s in the meal, and how it slows down digestion for fatty meals
  • how the brain detects if we’ve got enough fat and sugar stored away or if we need to eat
  • how the brain loses touch with our fat and sugar reserves—leading to obesity
  • how the brain loses touch with blood sugar levels—leading to diabetes

Michael has created a map of the neural circuits involved in controlling body weight. The map both explains the failure of past weight loss drugs and reveals many new drug targets.

He is the inventor of 10 families of patent applications, with 85 patents to date. And the company he founded, Orexigen Therapeutics, has four potential drugs for obesity under development with two at an advanced stage of trials.

Michael was headhunted back to Australia in 2008 by Monash University and VESKI (the Victorian Endowment for Science, Knowledge, and Innovation Fellowship).

“I hope to see one of our team’s discoveries become an effective therapy to treat obesity and diabetes, not just in the West but also in developing countries where billions of people are at risk,” he says.

Qualifications

1999                Doctor of Philosophy (Medicine), Monash University

1993                Bachelor of Science, Honours (Physiology), Monash University

1989                Bachelor of Science, The University of Melbourne

Career highlights, awards, fellowships and grants

2009–2014      Pfizer Australia Senior Research Fellowship

2008–present   Research Professor, Department of Physiology, Monash University

2009                High Blood Pressure Research Council of Australia Austin Doyle Lectureship

2008                Victorian Endowment for Science, Knowledge, and Innovation Fellowship

2008                Monash University STAR recruit

2007–2008      Associate Scientist, Oregon National Primate Research Center, Oregon Health and Science University, USA

2006–2008      Member, Heart Research and Diabetes Center, Oregon Health and Science University, USA

2002–2009      Founder, Chief Scientific Officer and Consultant, Orexigen Therapeutics, USA

2002–2007      Director, Electrophysiology Core, Oregon National Primate Research Center, Oregon Health and Science University, USA

2001–2007      Assistant Scientist, Oregon National Primate Research Center, Oregon Health and Science University, USA

2001–2007      Assistant Professor, Physiology and Pharmacology, Oregon Health and Science University, USA

2000–2002      Consultant, Neurocrine Biosciences, San Diego, USA

2000–2001      Research Assistant Professor, The Vollum Institute, Oregon Health and Science University, USA

1998–2000      Post-Doctoral Fellow, The Vollum Institute, Oregon Health and Science University, USA

1996                Queen Elizabeth II Silver Jubilee Trust for Young Australians, Queen’s Trust Achiever Award

1996                Queen Elizabeth II Silver Jubilee Trust for Young Australians, Future Perspectives Forum: Personal Responsibility for Australia’s Future

1996                Endocrine Society of Australia Travel Award

1994–1998      Graduate Student, Reproductive Neuroendocrinology, Monash University and Prince Henry’s Institute for Medical Research

Research highlights

Pioneered the use of patch clamp electrophysiology of genetically labelled neurons to analyse the actions of hormones on the brain

Created a circuit diagram of the metabolic control centres of the brain

Predicted that the gut peptide PYY3–36 would have anorexic and weight loss effects

Invented 10 families of patent applications (85 patents in total with 28 issued, the rest pending) around obesity drug screens and drug targets

Developed several drug targets including peptide YY, and several novel drug combinations including Naltrexone + Buproopion; both are now in phase 2/3 development

Founding intellectual property behind Thiakis Inc, recently acquired by Wyeth, and founder and chief scientific officer of Orexigen Therapeutics

Received 23 sponsored research awards with value in excess of $15 million

Has given 50 invited national and international lectures, published 40 original manuscripts and written 15 reviews

Memberships

Current            Member of the Society for Neuroscience, The Endocrine Society, the American Diabetes Association, Society for the Study of Ingestive Behavior, and The Obesity Society

2007-present   Senior Editor Neuroendocrinology, Member of the Editorial Board of Endocrinology, and The American Journal of Physiology, Member of SSIB program committee

2002–2007      Member of the editorial board of Obesity Research, and the executive committee of OHSU’s Neuroscience Graduate Program

1995–1996      Board of the Faculty of Medicine, Monash University

1994–1996      Vice President, then President of Prince Henry’s Institute Research Students’ Society

Photo Credit: Bearcage Productions

For more information:
http://www.med.monash.edu.au/physiology/staff/cowley.html