Gertsch Group

Institute of Biochemistry and Molecular Medicine, University of Bern, Switzerland

A ghost of signalling

A ghost of signalling
Jurg Gertsch - Tue Jan 03, 2012 @ 01:54PM
Comments: 1

Cells are made of proteins (among other things) and they interact with each other and change their properties. Proteins thus comunicate directly or indirectly and this communication is also called signalling (derived from Shannons theory of communication).

A good example are the MAP kinases, which interplay with each other via multiple phorsphorylation and dephosphorylation steps. In vitro this type of signalling can be studied relatively easily these days using gene and protein arrays. Today, whole journals are dedicated to cell signalling and thousands of papers dedicate their time to elucidate which signal leads to which signal and which one is a master switch in what context and so forth. I admit that when whole networks are studied this is very nice and has a big value on its own. A nice example is a recent paper on the self-organization and regulation of intrinsically disordered proteins with folded N-termini.

Experience in my lab shows that working with different cells you can get fantastic data (reproducible) one day and totally different data another day (again reproducible). For students this is very worrying and for me it's both worrying and interesting. It seems that these differences depend on the cell culture conditions and that there are close to chaotic processes involved, which basically make certain studies in cell signalling an art. Imagine that you need a complementary dataset for another experiment and you have two opposing datasets from signalling – would you chose the one that fits your wishful thinking? Or would you say that the data are strangely chaotic and beyond interpretation (or bullshit)? I just wonder whether a cell line in my lab ist he same cell line in your lab (at the level of signalling). You hear a critical undertone.

Maybe it’s the art of interpretation and the art of making big statements about something that is not much more than an in vitro artifact? This sounds like „Tamtam regulates Sharky which is a downstream modulator of Gugu – implications for cancer“ … just to give an fictive example. But what if in my lab Tamtam does not do anything and my antibody does not even recognize Gugu ? When I see (or review) studies in which artificially high concentrations of a pharmacological agent are studied at the level of signalling I always wonder whether this is real or not. Are the changes in gene expression or phosphorylation patterns in vitro really meaningful (robust or not robust)? It is our duty to do many experiments to find out. Imagine if your cells or a cell line from you tumour (in case you had cancer) would be useful to improve treatment of diseases. Unfortunately, the high hopes for a personalized medicine based on signalling (in vitro) was already kind of shattered by the discovery of the fraud  of papers in New England Journal of Medicine and Nature Medicine – signalling is a difficult business, a ghost. If you want to get to know it (the gost) have a look at this one …….. (my personal favourite on Cellular Signalling)!

Comments: 1

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