Professor Mark Febbraio is a Senior Principal Research Fellow and Investigator of the NHMRC and Head of the Cellular and Molecular Metabolism Laboratory within the Drug Discovery Program at Monash Institute of Pharmaceutical Sciences, at Monash University, Australia. He is also the CSO of N-Gene Research Laboratories Inc., a USA-based Biotechnology Company. His research focusses on understanding mechanisms associated with exercise, obesity, type 2 diabetes and cancer, with the aim of developing novel drugs to treat lifestyle-related diseases. Here he tells us about his unconventional route into research and how he helped start a new subfield of endocrinology!

Tell us about your career path so far

“Being a scientist is a balancing act between small wins and frequent disappointment. Experiments often don’t work out, papers are frequently rejected and grant applications are often not funded. The key is to savour the small wins.”

I didn’t take the conventional scientific path. After completing my undergraduate degree in exercise science, I became a full-time (semi-professional) triathlete. During a race in Japan, I become extremely heat stressed and dehydrated, so I decided to go back to do a PhD looking at the effect of environmental temperature on muscle metabolism during exercise. For the next 6 years, I worked as an exercise physiologist and undergraduate lecturer until I met Professor Bente Pedersen, a clinician from the University of Copenhagen, which got me into research. Since then, approximately 20 years ago, I’ve devoted 100% of my time to research as an NHMRC Research Fellow and Investigator in the area of tissue crosstalk, exercise and metabolic disease.

What inspired you into research?

Professor Bente Pedersen and I shared data that we had independently gathered showing that during exercise, muscle produces and releases IL-6, a cytokine previously thought to be made predominantly by immune cells in response to inflammation. We coined the term “myokine” (muscle-producing cytokine).

Muscle then became known as an endocrine organ. About 15 years earlier my friends and colleagues, Jeff Flier and Bruce Spiegleman, discovered that adipsin, a serine protease homolog, was synthesised and secreted by adipose tissue, and the field of adipokines was created. Muscle was a little late to the party but we got there eventually!

What are you proudest of in your career, so far?

Of course the IL-6 story was a proud moment, but our work on heat shock protein 70 as a therapeutic target for treating metabolic disease, as well as our recent work on extracellular vesicles and the synthesis of the chimeric protein IC7Fc to treat metabolic disease also make me proud.

What do you enjoy most about your work?

By far, training and interacting with my mentees. It has been wonderful to see so many great people transition through the laboratory and go on to be highly successful independent scientists.

What will you be presenting in your lecture at SfE BES 2021?

Basically, I will be presenting the historical story of how we came to discover that IC7Fc could be a viable treatment for metabolic disease. The story has many twists and turns!

“My feelings are that the next breakthrough will come from the global push towards artificial intelligence in drug discovery.”

I think the main challenge is that a complex problem like metabolic disease can’t be cured by simple solutions. Whilst “the molecular age” produced so much important knowledge, it become clear that there is no single molecule that, if targeted, will produce the magic bullet to treat or cure a disease that is so complex.

What do you think will be the next breakthrough in your field?

My feelings are that the next breakthrough will come from the global push towards artificial intelligence (AI) in drug discovery. I’m not saying that we will get the “slam dunk” from AI, but I’m sure we will learn so much via the big data revolution.

Any words of wisdom for aspiring endocrinologists?

Being a scientist is a balancing act between small wins and frequent disappointment. Experiments often don’t work out, papers are frequently rejected and grant applications are often not funded. The key is to savour the small wins and understand that the failures are part of building success. I often tell my trainees “in order to be successful you must be prepared to fail”. It’s OK, in fact it’s normal. Above all enjoy the process and don’t focus on the outcome.

You can attend Professor Mark Febbraio’s Medal Lecture, “Activation of the gp130 receptor: a panacea for the treatment of metabolic diseases?” on Tuesday 9 November at 09:00.

Find out more about the scientific programme for SfE BES 2021.