Identification of new mTORC1 and AMPK substrates
The enzymes mTORC1 and AMPK organize how cells respond to external stimuli like hormones and nutrients. However, how mTOR and AMPK do this is not known in detail. In this project we are looking for new proteins that are modified by mTOR and AMPK in muscle.
mTORC1 and AMPK are intracellular signaling proteins that transmit information in cells and have been shown to be central regulators of cellular function in both healthy cells and in a number of diseases. However, our understanding of the mechanisms behind the effects of AMPK and mTORC1 is inadequate. This also applies to skeletal muscle where AMPK and mTORC1 are also suggested to be important regulators of muscle adaptability to, for example, physical activity or various diseases.
In this project, in an international collaboration with researchers from the University of Sydney with mass spectrometry expertise, we conducted measurements of thousands of novel changes to proteins in mouse muscles with artificially activated AMPK or mTORC1. With the help of so-called machine learning algorithms we then "trained" a computer program to predict new AMPK and mTORC1 targets, thus identifying a long list of proteins likely to be controlled by AMPK or mTORC1.
We are currently following a number of these new proteins and mechanisms in cell culture, mice and human muscle biopsy material.
Novo Nordisk Foundation and the Danish Diabetes Academy.