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Mathias Uhlén

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Mathias Uhlén
EducationRoyal Institute of Technology, European Molecular Biology Laboratory
Scientific career
FieldsChemistry
Biology
Microbiology
Biotechnology
Biomedicine
InstitutionsRoyal Institute of Technology
Danish Technical University
Karolinska Institutet

Mathias Uhlén (born May 1954) is a Swedish scientist and Professor of Microbiology at Royal Institute of Technology (KTH), Stockholm.[1] After a post-doc period at the EMBL in Heidelberg, Germany, he became professor in microbiology at KTH in 1988. His research is focused on protein science, antibody engineering and precision medicine and range from basic research in human and microbial biology to more applied research, including clinical applications. He is member of several academies and societies, including Royal Swedish Academy of Science (KVA), National Academy of Engineering (NAE) and the Swedish Academy of Engineering Science (IVA). Dr Uhlen was the Founding Director of the national infrastructure Science for Life Laboratory (SciLifeLab) from 2010 to 2015.

Research

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His group was the first to describe a number of innovations in science including:

Protein engineering

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This broad concept of Affinity-based protein engineering was developed to use specific binding (affinity) of proteins in combination with protein engineering and it has led to many successful applications widely used in the life science community. This includes (A) engineered protein A[2] and protein G for purification of antibodies (B) affinity tags[3] for purification of recombinant fusion proteins (C) Affibodies[4] – clinically validated protein scaffold binders (D) the first solid phase methods for DNA handling using the biotin - streptavidin system [5] and (E) MabSelect SuRe – alkali-stabled matrix for purification of antibodies. This ligand has been used for the manufacturing of the majority of therapeutic antibodies on the market today.

Sequencing by synthesis

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This concept involves the detecting of the incorporation of nucleotides in real-time during synthesis by a DNA polymerase and to use this for DNA sequencing.  The concept, first described in 1993,[6] depends on several important underlying technologies, including attachment of DNA to solid supports, the use of engineered polymerases for synthesis a complementary nucleotide and the detection of the incorporated nucleotide to generate sequencing. This was used by the Pyrosequencing[7] method leading to the first massive parallel sequencing instrument (454). The concept of sequencing by synthesis is now used in all major “next generation sequencing” systems, including 454, PacBio, IonTorrent, Illumina and MGI.

Map of the human proteome

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The Human Protein Atlas program started in 2003 with the aim to contribute to the holistic understanding of all the proteins encoded from our DNA. The objective of the program is to map all the human proteins in cells, tissues, and organs using integration of various omics technologies, including antibody-based imaging, mass spectrometry-based proteomics, transcriptomics, and systems biology. The ultimate aim for the project is a complete understanding of the functions and interactions of all proteins and where in the different cells and tissues they reside. During the first 20 years, the open access resource has launched more than 5 million web pages with 10 million high-resolution microscope images, to allow individual researchers both in industry and academia to explore the proteome space across the human body.  The resource consists of various sections, spanning from tissues,[8] brain,[9] immune cells,[10] blood proteins, diseases and structures. The Tissue Atlas paper,[8] is one of the most cited publications from Europe in the last 10 years.

References

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  1. ^ "Mathias Uhlén". School of Engineering Sciences in Chemistry, Biotechnology and Health.
  2. ^ Uhlén, M.; Guss, B.; Nilsson, B.; Gatenbeck, S.; Philipson, L.; Lindberg, M. (1984-02-10). "Complete sequence of the staphylococcal gene encoding protein A. A gene evolved through multiple duplications". The Journal of Biological Chemistry. 259 (3): 1695–1702. doi:10.1016/S0021-9258(17)43463-6. ISSN 0021-9258. PMID 6319407.
  3. ^ Löwenadler, B; Nilsson, B; Abrahmsén, L; Moks, T; Ljungqvist, L; Holmgren, E; Paleus, S; Josephson, S; Philipson, L; Uhlén, M (September 1986). "Production of specific antibodies against protein A fusion proteins". The EMBO Journal. 5 (9): 2393–2398. doi:10.1002/j.1460-2075.1986.tb04509.x. ISSN 0261-4189. PMC 1167125. PMID 3096719.
  4. ^ Nord, Karin; Gunneriusson, Elin; Ringdahl, Jenny; Ståhl, Stefan; Uhlén, Mathias; Nygren, Per-Åke (August 1997). "Binding proteins selected from combinatorial libraries of an α-helical bacterial receptor domain". Nature Biotechnology. 15 (8): 772–777. doi:10.1038/nbt0897-772. ISSN 1087-0156. PMID 9255793. S2CID 25252394.
  5. ^ Uhlen, M. (August 1989). "Magnetic separation of DNA". Nature. 340 (6236): 733–734. Bibcode:1989Natur.340..733U. doi:10.1038/340733a0. ISSN 0028-0836. PMID 2770876. S2CID 4319266.
  6. ^ Nyren, P.; Pettersson, B.; Uhlen, M. (January 1993). "Solid Phase DNA Minisequencing by an Enzymatic Luminometric Inorganic Pyrophosphate Detection Assay". Analytical Biochemistry. 208 (1): 171–175. doi:10.1006/abio.1993.1024. PMID 8382019.
  7. ^ Ronaghi, Mostafa; Uhlén, Mathias; Nyrén, Pål (1998-07-17). "A Sequencing Method Based on Real-Time Pyrophosphate". Science. 281 (5375): 363–365. doi:10.1126/science.281.5375.363. ISSN 0036-8075. PMID 9705713. S2CID 26331871.
  8. ^ a b Uhlén, Mathias; Fagerberg, Linn; Hallström, Björn M.; Lindskog, Cecilia; Oksvold, Per; Mardinoglu, Adil; Sivertsson, Åsa; Kampf, Caroline; Sjöstedt, Evelina; Asplund, Anna; Olsson, IngMarie; Edlund, Karolina; Lundberg, Emma; Navani, Sanjay; Szigyarto, Cristina Al-Khalili (2015-01-23). "Tissue-based map of the human proteome". Science. 347 (6220): 1260419. doi:10.1126/science.1260419. ISSN 0036-8075. PMID 25613900. S2CID 802377.
  9. ^ Sjöstedt, Evelina; Zhong, Wen; Fagerberg, Linn; Karlsson, Max; Mitsios, Nicholas; Adori, Csaba; Oksvold, Per; Edfors, Fredrik; Limiszewska, Agnieszka; Hikmet, Feria; Huang, Jinrong; Du, Yutao; Lin, Lin; Dong, Zhanying; Yang, Ling (2020-03-06). "An atlas of the protein-coding genes in the human, pig, and mouse brain". Science. 367 (6482): eaay5947. doi:10.1126/science.aay5947. ISSN 0036-8075. PMID 32139519. S2CID 212560645.
  10. ^ Uhlen, Mathias; Karlsson, Max J.; Zhong, Wen; Tebani, Abdellah; Pou, Christian; Mikes, Jaromir; Lakshmikanth, Tadepally; Forsström, Björn; Edfors, Fredrik; Odeberg, Jacob; Mardinoglu, Adil; Zhang, Cheng; von Feilitzen, Kalle; Mulder, Jan; Sjöstedt, Evelina (2019-12-20). "A genome-wide transcriptomic analysis of protein-coding genes in human blood cells". Science. 366 (6472): eaax9198. doi:10.1126/science.aax9198. ISSN 0036-8075. PMID 31857451. S2CID 209424418.
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