Collins Lab Blog

Never say never

This figure, which I have taken from the reference below, absolutely blows my mind.

Temporal regulation of EGF signalling networks by the scaffold protein Shc1

Yong Zheng, Cunjie Zhang, David R. Croucher, Mohamed A. Soliman, Nicole St-Denis, Adrian Pasculescu, Lorne Taylor, Stephen A. Tate, W. Rod Hardy, Karen Colwill, Anna Yue Dai, Rick Bagshaw, James W. Dennis, Anne-Claude Gingras, Roger J. Daly & Tony Pawson

Nature 499, 166–171 (11 July 2013)

The figure summarizes the results of an experiment identifying Shc1 interactors. Every protein marked with an asterisk is a newly discovered interactor.

This phenomenal discovery was achieved with a mass spectrometry technique called “scheduled multiple reaction monitoring” or sMRM for short.

sMRM is one of those frustrating names that could mean a lot of things. Everybody knows what the words “scheduled”, “multiple” “reaction” and “monitoring” mean but which word goes with which? Is sMRM perhaps a sentence without verbs which really means “kinetic analysis of multiple independent samples simultaneously”? And how does “multiple samples simultaneously” differ from “technical replicates”? The technical details for the mass spectrometry identification are baffling, but it could be that the key protocol for the outcome of the experiment was the technical quality of the affinity purification.

One of the astonishing aspects to this discovery is the sheer number of new players in this pathway. In one fell swoop, the number of Shc1 interactors is more than doubled. For many well-studied biological systems. there is a lot of complacency that we are moving past the phase where we have uncovered all the major players.

Even for well-studied pathways it would be wise to be open to the possibility of the identification of novel participants whose involvement changes our understanding of a particular biological process.

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