02 Jul 2021
Enhancing the understanding of how diseases occur in one organ but not another
Peer review: Cell
Funding: National Health and Medical Research Council of Australia CJ Martin Fellowship
This study used animal models
A long-term collaboration between the Doherty Institute and the Foster and Gsponer laboratories at the University of British Columbia, Canada has used proteomics to map how proteins interact with each other in tissues revealing how the same protein, even when expressed in two tissues, can have dramatically different impacts.
Published today in Cell, the research team used mass spectrometry to provide a tissue-specific view of how protein-protein interactions are organised across seven tissues – the brain, heart, skeletal muscle, lung, kidney, liver, and thymus.
Co-author, Dr Nichollas Scott, a laboratory head at the Doherty Institute, said the findings have significantly advanced the understanding of how the same set of protein ‘parts’ can be differently arranged in cells across tissues.
“Proteins are like parts and although there is only a limited number of different types of parts in a given cell, how these can be put together in organisations known as protein complexes, can be quite different,” Dr Scott explained.
“And so, by characterising how the protein complexes of tissues are put together this can help us explain the functionality differences between tissues and why disease associated proteins can have certain impacts in one tissue over another.
“Using these findings, we have generated a resource for the community so that people can look at what each protein interacts with in different tissues to gain new insights into different disease models and better understand how a given protein works in their authentic states.”
These protein-protein interaction maps were built using a novel technique called protein correlation profiling which enabled the team to take protein complexes isolated from mouse tissues, separate them using size exclusion chromatography, then monitor which proteins are found together.
Then by using computational approaches and the concept of ‘guilt by association’ the team reconstructed the protein interaction networks in each tissue.
Up until now, most insights into protein interaction networks have been gained using cell culture-based systems, but these do not always mirror what is observed within tissues.
“Being able to use tissues to explore interaction networks enables us to get a better picture of how proteins are interacting with each other in a way which is a lot closer to what is actually happening in our own bodies,” Dr Scott highlighted.