Method development
Description
Methods and technologies for cell analysis are a cornerstone in research and healthcare, facilitating researchers in answering questions about the origins and progression of disease, and helping clinicians to set a correct diagnosis. Over the last two decades we have mainly focused on the development of methods; such as in situ PLA, ProxHCR and MolBoolean; to provide the ability to monitor protein-protein interactions and post-translational modifications in fixed cells and tissues, which is essential for the studies and understanding of cellular signaling. These methods use DNA as a reporter molecule and are based on natural occurring enzymes. Our current research explores the possibility to go beyond the boundaries of what nature can provide, to design enzymes that cannot be made through evolution. We have recently engineered a DNA-polymerase that isn´t compatible with life, that provides unique opportunities for development of novel methods for medical research.
Selected publications
Publications and Bibliometrics
Google scholar
https://scholar.google.se/citationsuser=XigDIwUAAAAJ&hl=en&oi=ao
Scopus:
https://www.scopus.com/authid/detail.uri?authorId=57204274888
Bivehed E, Hellman B, Wenson L, Stenerlöw B, Söderberg O & Heldin J
”Visualizing DNA single- and double-strand breaks in the Flash comet assay by DNA polymerase assisted end-labelling”
Nucleic Acid Res, 2024, in press
Raykova D, Kermpatsou D, Malmqvist T, Harrison PJ, Rubin Sander M, Stiller C, Heldin J, Leino M, Ricardo S, Klemm A, David L, Spjuth O, Vemuri K, Dimberg A, Sundqvist A, Norlin M, Klaesson A, Kampf C & Söderberg O
“A method for Boolean Analysis of Protein Interactions at a Molecular Level”
Nature Communications, 2022, 13(1):4755
Koos B, Cane G, Grannas K, Löf L, Arngården L, Heldin J, Clausson CM, Klaesson A, Hirvonen MK, Souza de Oliviera FM, Talibov V, Pham N, Auer M, Danielson H, Haybaeck J, Kamali-Moghaddam M & Söderberg O
“Proximity dependent initiation of hybridization chain reaction”
Nature Communications, 2015, 6, 7294
Leuchowius KJ, Clausson CM, Grannas K, Erbilgin Y, Botling J, Zieba A, Landegren U & Söderberg O.
”Parallel visualization of multiple protein complexes in individual cells in tumor tissue”
Mol Cell Proteomics, 2013, 12(6):1563-71.
Weibrecht I, Lundin E, Kiflemariam S, Mignardi M, Grundberg I, Larsson C, Koos B, Nilsson M & Söderberg O.
”In situ detection of individual mRNA molecules and protein complexes or post-translational modifications using padlock probes combined with the in situ proximity ligation assay”
Nature Protocols, 2013, 8(2): 355-72.
Weibrecht I, Gavrilovic M, Lindbom L, Landegren U, Wählby C & Söderberg O.
”Visualising individual sequence-specific protein-DNA interactions in situ”
N Biotechnol, 2012, 29(5): 589-598.
Clausson CM, Allalou A, Weibrecht I, Mahmoudi S, Farnebo M, Landegren U, Wählby C & Söderberg O.
”Increasing the dynamic range of in situ PLA”
Nature Methods, 2011, 8(11): 892-893.
Larsson C, Grundberg I, Söderberg O & Nilsson M.
”In situ detection and genotyping of individual mRNA molecules”
Nature Methods, 2010, 7(5): 395-397.
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.
”Detection of PDGF-receptor-β phosphorylation using a generalized proximity ligation method”
Mol Cell Proteomics, 2007, 6(9): 1500-1509.
Söderberg O, Gullberg M, Jarvius M, Ridderstråle K, Leuchowius KJ, Jarvius J, Wester K, Hydbring P, Bahram F, Larsson LG & Landegren U.
”Direct observation in situ of individual endogenous protein complexes by proximity ligation”
Nature Methods, 2006, 3(12): 995-1000.
Doctoral dissertations from the group
2010
Karl-Johan Leuchowius ” High Content Analysis of Proteins and Protein Interactions by Proximity Ligation”
http://uu.diva-portal.org/smash/get/diva2:301950/FULLTEXT01.pdf
2011
Irene Weibrecht “Visualizing Interacting Biomolecules In Situ”
http://uu.diva-portal.org/smash/get/diva2:410507/FULLTEXT01.pdf
2012
Agata Zieba “Application of Proximity Ligation Assay for Multidirectional Studies on Transforming Growth Factor Receptor-β Pathway”
http://uu.diva-portal.org/smash/get/diva2:513327/FULLTEXT01.pdf
2014
Carl-Magnus Clausson “Making Visible the Proximity Between Proteins”
http://uu.diva-portal.org/smash/get/diva2:695615/FULLTEXT01.pdf
2015
Karin Grannas “Improvements and Applications of in situ Proximity Ligation Assays”
http://uu.diva-portal.org/smash/get/diva2:801280/FULLTEXT01.pdf
2016
Linda Arngården “Analysis of signaling pathway activity in single cells using the in situ Proximity Ligation Assay”
http://uu.diva-portal.org/smash/get/diva2:915351/FULLTEXT01.pdf
2018
Axel Klaesson “Development of DNA-based methods for analysis of protein interactions”
http://uu.diva-portal.org/smash/get/diva2:1177746/FULLTEXT01.pdf
2023
Despoina Kermpatsou ”Method development for analysis of protein interactions”
http://uu.diva-portal.org/smash/get/diva2:1712557/FULLTEXT01.pdf
Mattias Leino “Advancing DNA-based proximity methods”
http://uu.diva-portal.org/smash/get/diva2:1740390/FULLTEXT01.pdf
Marie Rubin Sander “Analysis of PDGF receptor internalization and signaling using proximity ligation assays”
http://uu.diva-portal.org/smash/get/diva2:1742559/FULLTEXT01.pdf
Publications
Part of Journal of Steroid Biochemistry and Molecular Biology, 2024
- DOI for Cellular responses to silencing of PDIA3 (protein disulphide-isomerase A3): Effects on proliferation, migration, and genes in control of active vitamin D
- Download full text (pdf) of Cellular responses to silencing of PDIA3 (protein disulphide-isomerase A3): Effects on proliferation, migration, and genes in control of active vitamin D
Part of Biochemical and Biophysical Research Communications - BBRC, 2024
The method developer's guide to oligonucleotide design
Part of Expert Review of Proteomics, p. 65-80, 2024
Part of Nucleic Acids Research, 2024
Part of Biochemical and Biophysical Research Communications - BBRC, p. 195-201, 2023
- DOI for Activated EGFR and PDGFR internalize in separate vesicles and downstream AKT and ERK1/2 signaling are differentially impacted by cholesterol depletion
- Download full text (pdf) of Activated EGFR and PDGFR internalize in separate vesicles and downstream AKT and ERK1/2 signaling are differentially impacted by cholesterol depletion
Large-scale phage-based screening reveals extensive pan-viral mimicry of host short linear motifs
Part of Nature Communications, 2023
Purification of DNA oligonucleotides to improve hybridization chain reaction performance
Part of New Biotechnology, p. 33-40, 2023
A method for Boolean analysis of protein interactions at a molecular level
Part of Nature Communications, 2022
Part of Cellular Signalling, 2022
- DOI for Differential impact of lipid raft depletion on platelet-derived growth factor (PDGF)-induced ERK1/2 MAP-kinase, SRC and AKT signaling
- Download full text (pdf) of Differential impact of lipid raft depletion on platelet-derived growth factor (PDGF)-induced ERK1/2 MAP-kinase, SRC and AKT signaling
Part of Analytical Chemistry, p. 1842-1850, 2021
Part of Mutation research. Genetic toxicology and environmental mutagenesis, 2020
Dynamin inhibitors impair platelet-derived growth factor beta-receptor dimerization and signaling
Part of Experimental Cell Research, p. 69-79, 2019
Part of Journal of Experimental Biology, 2019
Part of Molecular Systems Design & Engineering, p. 1058-1065, 2019
Improved efficiency of in situ protein analysis by proximity ligation using UnFold probes
Part of Scientific Reports, 2018
Part of Current Protocol in Cytometry, 2017
Flow Cytometric Measurement of Blood Cells with BCR-ABL1 Fusion Protein in Chronic Myeloid Leukemia
Part of Scientific Reports, p. 1-9, 2017
Insufficient antibody validation challenges oestrogen receptor beta research
Part of Nature Communications, 2017
Part of Molecular Diagnostics (Third Edition), p. 219-231, Academia Press, 2017
Antagonists of IGF: Vitronectin Interactions Inhibit IGF-I-Induced Breast Cancer Cell Functions
Part of Molecular Cancer Therapeutics, p. 1602-1613, 2016
Part of Haematologica, p. 668-669, 2016
Part of Scientific Reports, 2016
Part of Proteomes, 2016
Part of Molecular & Cellular Proteomics, p. 1848-1856, 2016
The protein kinase LKB1 negatively regulates bone morphogenetic protein receptor signaling
Part of Oncotarget, p. 1120-1143, 2016
Part of British journal of virology, p. 11-23, 2016
Closing in on life - proximity dependent methods for life sciences
Part of Oncotarget, p. 17867-17868, 2015
Part of Scientific Reports, 2015
Crosstalk between Hippo and TGF beta: Subcellular Localization of YAP/TAZ/Smad Complexes
Part of Journal of Molecular Biology, p. 3407-3415, 2015
Part of Molecular Oncology, p. 503-512, 2015
E-cadherin can limit the transforming properties of activating beta-catenin mutations
Part of EMBO Journal, p. 2321-2333, 2015
Functional loss of IκBε leads to NF-κB deregulation in aggressive chronic lymphocytic leukemia
Part of Journal of Experimental Medicine, p. 833-843, 2015
Next-Generation Pathology: Surveillance of Tumor Microecology
Part of Journal of Molecular Biology, p. 2013-2022, 2015
Proximity-dependent initiation of hybridization chain reaction
Part of Nature Communications, 2015
Analysis of protein interactions in situ by proximity ligation assays
Part of High-Dimensional Single Cell Analysis, p. 111-26, Springer, 2014
Part of PLOS ONE, 2014
- DOI for Fine-Tuning of Smad Protein Function by Poly(ADP-Ribose) Polymerases and Poly(ADP-Ribose) Glycohydrolase during Transforming Growth Factor β Signaling
- Download full text (pdf) of Fine-Tuning of Smad Protein Function by Poly(ADP-Ribose) Polymerases and Poly(ADP-Ribose) Glycohydrolase during Transforming Growth Factor β Signaling
Part of Blood, 2014
Part of PLOS ONE, 2013
Part of Nature Protocols, p. 355-372, 2013
Parallel Visualization of Multiple Protein Complexes in Individual Cells in Tumor Tissue
Part of Molecular & Cellular Proteomics, p. 1563-1571, 2013
Part of Journal of Pathology, p. 705-718, 2013
Part of New Biotechnology, p. 144-152, 2013
Part of Oncogene, p. 3606-3615, 2013
Part of European Journal of Human Genetics, p. 301-309, 2013
Part of Arteriosclerosis, Thrombosis and Vascular Biology, p. 1255-1263, 2012
Part of Journal of Cellular and Molecular Medicine, p. 1474-1484, 2012
Part of Molecular & Cellular Proteomics, 2012
Part of The EPMA journal, 2012
Molecular tools for companion diagnostics
Part of New Biotechnology, p. 634-640, 2012
Part of Journal of Pathology, p. 378-390, 2012