Uppsala University, Uppsala, Sweden

Description of organization

Uppsala University is a leading comprehensive research university in Sweden, founded 1477 and oldest in northern Europe. Research is strong in many fields including biology, biomedicine, material science and computer science, with a strong tradition for development of technologies for biological analyses. The Molecular Medicine research group, located at the Rudbeck laboratory, focuses on developing molecular and micromechanical tools for high-precision analysis of genes and proteins.

Department of Immunology, Genetics and Pathology

Previous experience and profile of staff members

Headed by Professor Ulf Landegren, it has pioneered a number of important molecular techniques, some of which have been licensed for industrial applications and clinical analyses. They include the oligonucleotide ligation assay (OLA), padlock probes for parallel or localized genetic analyses, used directly or amplified via PCR or rolling circle replication, and the proximity ligation technique (PLA) for highly specific protein analyses. These techniques have been licensed to companies such as Applied Biosystems and General Electric HealthCare, and by companies founded by Professor Landegren (Quiatech AB, ParAllele Bioscience Inc, and Olink Bioscience AB. The Current research in the Landegren group is focused on technologies for high-throughput analyses of genes, transcripts, and proteins, and for detection of the location of single or interacting molecules. In particular, the proximity ligation mechanism is used to convert complex protein analytic problems to more tractable analyses of surrogate DNA strands. Landegren has served on SABs of several biotech companies. He is visiting senior scientist at the RIKEN Inst, Yokohama, Japan and member of EMBO and the Swedish Royal Academy of Sciences. He coordinated the EU FP6 IP MolTools, aimed at developing a series of new molecular analytical procedures. He has published more than 120 scientific publications, and is the inventor on 22 patents and patent applications. The Molecular Diagnostic group, headed by Professor Mats Nilsson develops PLP and selector probe assays and has expertise in developing highly selective molecular detection assays based on analytical DNA ligation reactions including developing isothermal RCA-based DNA amplification reactions, tailored for the ligation-based detection reactions and developing detection readout formats tailored for the ligation- and RCA-based molecular detection and amplification reactions. Professor Nilsson is an experienced developer of molecular genetics techniques with strong experience in large-scale collaborative projects. Mats Nilsson is author of more than 60 peer-reviewed articles and has previously coordinated several large EU projects. U. Landegren, M. Nilsson and their coworkers have co-founded five biotech companies, including ParAllele, acquired by Affymetrix in 2005, Olink Bioscicence, Olink Genomics and Q-linea. Landegren and Nilsson will contribute expertise on imaging nucleic acids and proteins in cells and tissues using their highly resolving molecular tools. Via the technique of in situ sequencing, mutations can be recorded directly in tissues with cellular resolution, and large numbers of reacted probes can be identified via tag sequences. They will also provide access to padlock and proximity ligation techniques for measuring proteins, transcripts and molecular complexes in solution phase, at very high levels of multiplexing. The techniques are suitable for validating biomarkers in large groups of samples. Finally, the lab is also developing techniques for targeted resequencing of genomic regions of interest for mutation detection and methylation analysis.

Webpage

Department of Immunology, Genetics and Pathology, Uppsala University

Recent publications relevant to the project

1. Fredriksson S, Gullberg M, Jarvius J, Olsson C, Pietras K, Östman A, Landegren U. Protein detection using proximity-dependent DNA ligation assays. Nature Biotechnology 20: 473-477 (2002).

2. Gullberg M, Gústafsdóttir SM, Schallmeiner E, Jarvius J, Bjarnegård M, Betsholtz C, Landegren U, Fredriksson S. Cytokine detection by antibody-based proximity ligation. Proceedings of the National Academy of Sciences USA 101: 8420-8424 (2004).

3. Söderberg O, Gullberg M, Jarvius M, Ridderstråle K, Leuchowius KJ, Jarvius J, Wester K, Hydbring P, Bahram F, Larsson LG, Landegren U. Direct observation of individual endogenous protein complexes in situ by proximity ligation. Nature Methods 3: 995-1000 (2006).

4. Jarvius M, Paulsson J, Weibrecht I, Leuchowius KJ, Andersson AC, Wählby C, Gullberg M, Botling J, Sjöblom T, Markova B, Östman A, Landegren U, Söderberg O. In situ detection of phosphorylated PDGF receptor β using a generalized proximity ligation method. Molecular and Cellular Proteomics 6: 1500-1509 (2007).

5. Darmanis S, Nong RY, Hammond M, Alderborn A, Vänelid J, Gustafsdottir S, Ericsson O, Landegren U, Kamali-Moghaddan M. Sensitive plasma protein analysis by microparticle-based proximity ligation assays. Molecular and Cellular Proteomics, 9:327- 335, 2009

Department of Information Technology

The Department of Information Technology at Uppsala University
is unique in its breadth. Our activities span from the gathering, management, and analysis of data via
signal and image processing, scientific computing and control engineering, to communication of results
with the aid of database management and human-computer interaction. A common ground is provided
by methodological research in theoretical computing science, real-time systems, and computer
architecture. A total of more than 200 researchers are active at the department including more than 25
full professors. A large part of the research at the department has by a recent international evaluation
been classified as world-leading or world-class.