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Department of Genetics, Microbiology and Toxicology (GMT) Radiation Biology Prof. Andrzej Wojcik Prof. Mats Harms-Ringdahl Toxicology Prof. Thomas Helleday Prof. Ulf Rannug Prof. Dag Jenssen / Dag Jenssen, GMT Centre for Radiation Protection Research (CRPR) Molecular Mechanisms in Cancer Radiation Biology (AW & MHR) 2 Profs 1 Postdoc 5 PhD students 2 Master students Mechanisms of cellular and systemic effects of exposure to ionising radiation EU grants Swedish Radiation Safety Authority Radiation Biology (AW & MHR) Mechanisms of individual sensitivity to ionising radiation: • Differences in DNA-damage response pathways between cohorts of patients with normal or severe healthy tissue reactions to tumour therapy. • Screening for polymorphisms in genes for DNArepair, cell cycle regulation and apotosis • Search for diagnostic tools to identify the persons at risk. Patient with severe side-effect following radiotherapy Radiation Biology (AW & MHR) What are the risks of radiation at low doses? Can we improve biological dosimetry? Is the dose response curve non-linear? Identification of new response pathways for very low doses. Epidemiological data (excess cancers) ? (above background) New technologies will determine doses with high precision? New biomarkers for DNAdamage response pathways Professor Thomas Helleday’s group SU group 1 Prof 10 Postdocs & senior scientists 8 PhD students 1 Master students Oxford group 6 Postdocs 7 DPhil students DNA repair in cancer therapy Main grants from: Swedish Scientific Research Council (VR) Swedish Pain Relief Foundation (Smärtafonden) Swedish Cancer Foundation (Cancerfonden) Swedish Children’s Cancer Foundation (Barncancerfonden) SU - DNA Repair team Niklas Schultz, Helge Gad, Fredrik Johansson, Anne Lagerkvist, Linda Savolainen, Ingegerd Elvers, Cecilia Ström, Petra Groth, Firas Al-Ubadi, Ivaylo Stoimenov, Kristian Grimberg, Guoli Liu, Muntasir Mamun Research areas • • • • Stalling of Replication fork and Replication Restart Homologous recombination DNA replication termination DNA repair in cancer (cells + clinical material) SU - Biochemistry/proteomics Ann-Sofie Jemth, Olga Loseva Research areas • Poly (ADP ribose) polymerases • Proteomics after DNA damage • Purification of protein targets for cancer treatment SU – Cancer Biology Tatjana Djureinovic, Evgenia Gubanova Research areas • DNA damage signalling in cancer • Evaluation of targets for cancer treatment SciLifeLab - High-Throughput Screening Bo Lundgren Research areas • RNAi library screens in cells • Identify targets for cancer treatments • Map functional genetic networks SU – Medical Chemistry Martin Scobie, Tobias Koolmeister Research areas • Lead optimisation - Parallell organic chemistry synthesis Professor Ulf Rannugs group 1 1 3 1 Prof Postdoc PhD students Master student Natural non-persistent bioactive aryl hydrocarbon receptor ligands in humans The Swedish research Council FORMAS Professor Ulf Rannug, cont. Formation and metabolism of the suggested physiological Ah receptor ligand 6-formylindolo[3,2-b]carbazole (FICZ) HPLC, LC/MS/MS Recombinant human enzymes Human cells in vitro Human blood, plasma and urine samples NFĸB AhR Professor Ulf Rannug, cont. The new AhR paradigm TRYPTOPHAN TRYPTAMINE PROLIFERATION/APOPTOSIS OTHER RECEPTORS (LXR) DEVELOPMENT DIFFERENTIATION I-3-A FICZ Active ligand CYP1 ARYL HYDROCARBON RECEPTOR (AhR) Genomic and non-genomic regulation HOMEOSTASIS IMMUNE RESPONS INFLAMMATION STRESS RESPONSES AOX NEUROENDOCRINE oxFICZ Inactiveligand SECOND MESSENGERS FUNCTIONS Professor Dag Jenssen’s group 2 2 2 3 Profs Postdocs PhD students Master students Molecular/cellular mechanisms for induced mutations EU grants Swedish Cancer Society Swedish Radiation Protection Authority / Dag Jenssen, GMT Professor Dag Jenssen, cont. Mechanisms involved in the repair of genomic DNA intra-strand cross-links (Cf, 2010-2013) Cell culture models DNA repair DNA replication Mutation assay DNA sequencing The basis for cancer risk assessment of lifestyle factors / Dag Jenssen, GMT Professor Dag Jenssen, cont. Molecular/cellular protection mechanisms against carcinogenic constituents in food (EU, 2010-2014) The basis for developing Functional Foods / Dag Jenssen, GMT