Swedish technological breakthrough poised to open new field in protein science research

Yet another major contribution from the Stockholm-Uppsala region to accelerating personalized medicine

An exciting new protein research method has been developed by Associate Professor Janne Lehtiö’s team at SciLifeLab in Stockholm and published in Nature Methods. The new method allows in-depth analysis of complex protein samples and has resulted in the discovery of 98 unknown human protein-coding genes or gene variants. In particular, several of the proteins were shown to be coded by so-called pseudogenes or “junk genes”, considered previously to lack any purpose. Further research using the new method includes investigating whether these protein-coding genes can be used as biomarkers in cancer or other diseases. Lehtio’s team has already used the method for deep human proteome analysis in cancer research, resulting in the identification of retinoic acid receptor alpha (RARA) as a biomarker for tamoxifen treatment response in breast cancer in a study published in Nature Communications this summer.

This new method builds on a rich history of protein science research in the region, says Ola Björkman from Stockholm-Uppsala Life Science.
“It all started more than 80 years ago with the ultracentrifuge, developed by Nobel laureate The Svedberg, followed by another Nobel Prize awarded innovation (electrophoresis by Professor Tiselius) and the growth of a strong industrial base, now carried forward by GE Healthcare Life Sciences and other companies. More recent innovations developed in the region include pyrosequencing, proximity ligation and the development of recombinant proteins for culturing stem cells. Last but not least, the on-going Protein Atlas project which has already amassed information on more than 17,000 antibodies, targeting proteins from more than 14,000 human genes (~70% of the human protein-coding genes) would probably not have been possible without the protein science competence base in the region.”
According to Associate Professor at Karolinska Institutet and study leader Janne Lehtiö, collaboration has been key to the development.
“To be able to do this we had to match experimental data for sequences of peptides with millions of possible locations in the whole genome. And we had to develop both new experimental and bioinformatics methods to allow protein based gene detection. To have GE Healthcare Life Sciences experts and instruments on site at SciLifeLab was also important.
“Now, when we have the technology in place it feels like participating in a Jules Verne adventure inside the genome,” continues Lehtiö, “and we are eager to apply this technology to further explore how these proteins, encoded by hitherto oftenreferred to as 'junk DNA', might be involved in different kinds of diseases. And, if this is the case, a whole new arena for developing novel biomarker tools opens up.”

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