21 mars 2013: Prof. Mathias Uhlén

Thursday, March 21st 2013, 12h30

Prof. Mathias UHLÉN
Director of Science for Life Laboratory
Royal Institute of Technology (KTH), Stockholm


"Exploring the Proteome to Understand Human Biology and Disease"

The human genome has approximately 20,000 protein-encoded genes. An import quest for the future is to characterize the expression, localization, modification and function of at least one representative protein from each gene and recently a Human proteome Project has been launched to coordinate such an international effort (1). The Human Protein Atlas project involving groups in Sweden, Korea, China and has decided to join the HPP and to contribute by performing antibody-based profiling in a proteome-wide manner (2). The aim is to generate a first draft on a whole-proteome level of protein localizations in human cells, tissues and organs, including various disease-related tissues. The current version 11.0 of the Human Protein Atlas (www.proteinatlas.org) contains more than 18,000 validated antibodies targeting 15,000 genes corresponding to 75% of the protein-encoded genes in humans (3). The Protein Atlas contains more than 13 million high-resolution images generated by immunohistochemistry and confocal microscopy. The antibodies have been generated to regions of low homology (4,5) and the long-term objective is to generate paired antibodies towards the protein targets with separate and non-overlapping epitopes (6) to provide protein evidence for all human protein-coding genes (7). Pilot projects have been initiated to also generate recombinant affinity reagents (6,8), a pilot version of a Rodent Brain Protein Atlas (9) and to study human biology (10). In addition, we have developed a targeted MS-proteomics strategy based on the recombinant protein fragments (PrESTs) generated within the frame-work of the Protein Atlas project (11). We have used the human protein atlas to study the global protein expression patterns in human cells, tissues and organs (12,13) as well as a discovery tool to find potential biomarkers for cancer diagnostics and to develop new potential antibodies for therapeutics.

Selected own references:

1. Paik et al (2012) Nature Biotechnology 30(3):221-3.
2. Uhlen et al (2012) Mol Cell Proteomics. 11(3):M111.013458.
3. Uhlen et al (2010) Nature Biotechnology 28(12):1248-50
4. Rockberg and Uhlen (2009) Protein Science 18(11): 2346-55.
5. Rockberg et al (2009) Nature Methods 5(12): 1039-45
6. Uhlen et al (2008) Nature Methods 5 (10): 854-855
7. Fagerberg et al (2013) J of Proteomics Res, in press (on-line)
8. Bourbeillon et al (2010) Nature Biotechnology 28(7): 650-3.
9. Mulder et al (2009) Proc Natl Acad Sci USA 106: 22492-7.
10. Vashisht et al (2009) Science 326:718-21.
11. Zeiler et al (2012). Mol Cell Proteomics, 11(3): O111.009613.
12. Lundberg et al (2010) Molecular Systems Biology 6:450-459
13. Ponten et al (2009) Molecular Systems Biology 5:337-346

Dr Uhlén received his PhD in chemistry at the Royal Institute of Technology (KTH), Stockholm, Sweden.
After a post-doc period at the EMBL in Heidelberg, Germany, he became professor in microbiology at KTH in 1998. Dr Uhlén has more than 350 publications in bioscience with the focus on the development and use of affinity reagents in biotechnology and biomedicine.

In the eighties, he was the first to describe the use of affinity tags for purification of proteins, a principle now widely used in bioscience.
In the 90ies, his group described a new strategy for DNA analysis called Pyrosequencing, a method that was further developed by a US company (454/Roche) into the first of a new generation of next generation sequencing methods. His group also developed a new affinity reagent called Affibodies, based on combinatorial principles and, in addition, developed alkali-stable variations of protein A, now commercially available for purification of antibodies (MabSelectSure).

In the early 2000, his group started an international effort, with groups in Sweden, India, China and South Korea, for the creation of a Human Protein Atlas (www.proteinatlas.org) with the aim to systematically map the human proteome with antibodies.

Dr Uhlén is member of the Royal Swedish Academy of Engineering Science (IVA), the Royal Swedish Academy of Science (KVA), the European Molecular Biology Organization (EMBO) and member of the Human Proteome Organization (HUPO) council. He was Vice-President of the Royal Institute of Technology (KTH), responsible for external relations, from 1999 to 2001.

Recently, he became the Director of a new center Science for Life Laboratory Stockholm for high-throughput bioscience (www.scilifelab.org).

He has received numerous awards, including the Göran Gustavsson prize, the Gold Medal of the Royal Swedish Academy of Engineering Sciences, the Akzo Noble Award, the HUPO Distinguished Award, the KTH Great Prize, the ABRF award, the Scheele prize and the H.M. the King’s Medal with the ribbon of the Order of Seraphim.