Discovery and characterisation of novel myokines using innovative proteomic analysis

• Applicant: Dr. Martin Pal
• Subject Area: Endocrinology, Diabetology, Metabolism ; Evolutionary Cell and Developmental Biology (Zoology)
• Term: from 2013 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 247690333

Obesity is associated with the development of metabolic disorders, including insulin resistance and type II diabetes. Despite the known efficacy of exercise in preventing and treating these conditions, this therapeutic approach and research into the mechanisms involved, is surprisingly overlooked. In recent years, work in the host laboratory and others, has given rise to the concept of the myokine, a protein produced and released from contracting skeletal muscle in order to orchestrate the beneficial effects of exercise on metabolic disorders. Since the identification of the proto-typical myokine IL-6, a select number of myokines have been described, but often discovered serendipitously. Hence, this study aims to identify novel myokines which are secreted by the skeletal muscle in response to exercise and importantly, determine their biological relevance. To this end, in a first step the proteome of an exercising mouse will be compared with the proteome of a rested mouse. To facilitate the in vivo detection of released myokines, the innovative proteomic stable isotope labelling with amino acids in cell culture (SILAC) spike-in approach will be adopted, using prepared muscle lysates from in vitro and in vivo SILAC labelling experiments carried out at the host laboratory. Proteins exhibiting an exercise response will then be interrogated for secretory sequences via bioinformatical analyses. The significance of putative myokines on metabolic function will then be assessed in vitro and in vivo by metabolic screening experiments. The putative novel myokines identified by this research project will provide therapeutic targets and help to understand the beneficial effects of exercise on disease conditions, such as insulin resistance and type II diabetes.

• DFG Programme: Research Fellowships
• International Connection: Australia
• Host: Professor Mark Febbraio, Ph.D.