Mathias Uhlén
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Mathias Uhlén (born May 1954) is a Swedish scientist and Professor of Microbiology at Royal Institute of Technology (KTH), Stockholm. After a post-doc period at the
EMBL The European Molecular Biology Laboratory (EMBL) is an intergovernmental organization dedicated to molecular biology research and is supported by 29 member states, two prospect member states, and one associate member state. EMBL was created in ...
in Heidelberg, Germany, he became professor in
microbiology Microbiology () is the branches of science, scientific study of microorganisms, those being of unicellular organism, unicellular (single-celled), multicellular organism, multicellular (consisting of complex cells), or non-cellular life, acellula ...
at KTH in 1988. His research is focused on protein science, antibody engineering and
precision medicine Precision, precise or precisely may refer to: Arts and media * ''Precision'' (march), the official marching music of the Royal Military College of Canada * "Precision" (song), by Big Sean * ''Precisely'' (sketch), a dramatic sketch by the Eng ...
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

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


Protein engineering

This broad concept of Affinity-based
protein engineering Protein engineering is the process of developing useful or valuable proteins through the design and production of unnatural polypeptides, often by altering amino acid sequences found in nature. It is a young discipline, with much research taking pl ...
was developed to use specific binding (
affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Pa ...
) 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 Protein A is a 42 kDa surface protein originally found in the cell wall of the bacteria ''Staphylococcus aureus''. It is encoded by the ''spa'' gene and its regulation is controlled by DNA topology, cellular osmolarity, and a two-component syst ...
and
protein G Protein G is an immunoglobulin-binding protein expressed in group C and G streptococcal bacteria much like protein A but with differing binding specificities. It is a ~60-kDA (65 kDA for strain G148 and 58 kDa for strain C40) cell surface pro ...
for purification of antibodies (B) affinity tags for purification of recombinant
fusion protein Fusion proteins or chimeric (kī-ˈmir-ik) proteins (literally, made of parts from different sources) are proteins created through the joining of two or more genes that originally coded for separate proteins. Translation of this '' fusion gene'' ...
s (C) Affibodies – clinically validated protein scaffold binders (D) the first solid phase methods for DNA handling using the
biotin Biotin (also known as vitamin B7 or vitamin H) is one of the B vitamins. It is involved in a wide range of metabolic processes, both in humans and in other organisms, primarily related to the utilization of fats, carbohydrates, and amino acids. ...
-
streptavidin Streptavidin is a 52 Atomic mass unit, kDa protein (tetramer) purified from the bacterium ''Streptomyces avidinii''. Streptavidin Homotetramer, homo-tetramers have an extraordinarily high affinity for biotin (also known as vitamin B7 or vitamin ...
system 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 Monoclonal antibodies (mAbs) have varied therapeutic uses. It is possible to create a mAb that binds specifically to almost any extracellular target, such as cell surface proteins and cytokines. They can be used to render their target ineffective ...
on the market today.


Sequencing by synthesis

This concept involves the detecting of the incorporation of nucleotides in real-time during synthesis by a
DNA polymerase A DNA polymerase is a member of a family of enzymes that catalyze the synthesis of DNA molecules from nucleoside triphosphates, the molecular precursors of DNA. These enzymes are essential for DNA replication and usually work in groups to create t ...
and to use this for
DNA sequencing DNA sequencing is the process of determining the nucleic acid sequence – the order of nucleotides in DNA. It includes any method or technology that is used to determine the order of the four bases: adenine, thymine, cytosine, and guanine. The ...
.  The concept, first described in 1993, depends on several important underlying technologies, including attachment of DNA to solid supports, the use of engineered polymerases for synthesis a complementary
nucleotide Nucleotides are Organic compound, organic molecules composed of a nitrogenous base, a pentose sugar and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both o ...
and the detection of the incorporated nucleotide to generate sequencing. This was used by the
Pyrosequencing Pyrosequencing is a method of DNA sequencing (determining the order of nucleotides in DNA) based on the "sequencing by synthesis" principle, in which the sequencing is performed by detecting the nucleotide incorporated by a DNA polymerase. Pyrosequ ...
method leading to the first
massive parallel sequencing Massive parallel sequencing or massively parallel sequencing is any of several high-throughput approaches to DNA sequencing using the concept of massively parallel processing; it is also called next-generation sequencing (NGS) or second-generation ...
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

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 Imaging is the representation or reproduction of an object's form; especially a visual representation (i.e., the formation of an image). Imaging technology is the application of materials and methods to create, preserve, or duplicate images. ...
,
mass spectrometry Mass spectrometry (MS) is an analytical technique that is used to measure the mass-to-charge ratio of ions. The results are presented as a ''mass spectrum'', a plot of intensity as a function of the mass-to-charge ratio. Mass spectrometry is used ...
-based
proteomics Proteomics is the large-scale study of proteins. Proteins are vital macromolecules of all living organisms, with many functions such as the formation of structural fibers of muscle tissue, enzymatic digestion of food, or synthesis and replicatio ...
,
transcriptomics Transcriptomics technologies are the techniques used to study an organism's transcriptome, the sum of all of its RNA, RNA transcripts. The information content of an organism is recorded in the DNA of its genome and Gene expression, expressed throu ...
, and
systems biology Systems biology is the computational modeling, computational and mathematical analysis and modeling of complex biological systems. It is a biology-based interdisciplinary field of study that focuses on complex interactions within biological system ...
. 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, brain, immune cells, blood proteins, diseases and structures. The Tissue Atlas paper, is one of the most cited publications from Europe in the last 10 years.


References

{{DEFAULTSORT:Uhlen, Mathias 1954 births Living people Swedish microbiologists KTH Royal Institute of Technology alumni Academic staff of the KTH Royal Institute of Technology