Curriculum Vitae PERSONAL INFORMATION Joachim Frey WORK EXPERIENCE August 2016- Present Programme collaborator Swiss National Science Foundation SNF (Switzerland) President of the Steering Committee of the National Research Programme NRP 72 "Antimicrobial Resistnace" July 1996-July 2016 Professor University of Bern (Switzerland) Teaching, Research and Diagnostics in Veterinary Bacteriology Research topics Molecular mechanisms of bacterial virulence, Infection and inflammation; Microbiology; Genetics and Biochemistry; Vaccine development; Gene array technologies; Bacterial protein toxins, Adhesins and immunogenic factors; Bacteria-host interactions in pathogenesis; Biological safety aspects of natural and genetically modified organisms. The research topics involve: a)Biochemical and genetic study of virulence factors of Actinobacillus pleuropneumoniae. Purification of major toxins, cloning, toxicity on polymorph nuclear neutrophils and macrophages, construction of derivative strains deleted for their virulence genes, protective antigens, elaboration of concepts for live vaccines. b)Genetic and antigenic investigations on Mycoplasma hyopneumoniae and Mycoplasma conjunctivae: Molecular epidemiological methods, Sensitive diagnostics and disease control. c)Mycoplasma mycoides subsp. mycoides SC: Adhesion, mechanisms of virulence, specific antigens. Impact of metabolic pathway products in virulence. d)Virulence factors and epidemiological markers of ruminants Mycoplasmas. e)Type III secretion systems and effector proteins of inflammatory processes in Aeromonas salmonicida and other fish pathogenic Aeromonas species f)Clostridium chauvoei and Clostridium septicum: analysis of major virulence factors. g)Gene probes for the detection of bacterial virulence factors and antibiotic resistance (Bio-safety assessment). h)Recombinant vaccine against botulism in horses. i)Molecular typing of Bacillus anthracis and Francisella tularensis j)Detection and genetics of Brachyspira sp. and Dichelobacter nodosus. May 1987-June 1996 Researcher, Principal Investigator University of Bern (Switzerland) Research on molecular mechanisms of bacterial virulence. Specific research on Actinobacillus pleuropneumoniae and Mycoplasma hyopneumoniae August 2016- Present Professor emeritus University of Bern (Switzerland) Research topics Molecular mechanisms of bacterial virulence, Infection and inflammation; Microbiology; Genetics and Biochemistry; Vaccine development; Gene array technologies; Bacterial protein toxins, Adhesins and immunogenic factors; Bacteria-host interactions in pathogenesis; Biological safety aspects of natural and genetically modified organisms. Risk assessment for microbes and biological safety laboratories The research topics involve: a)Biochemical and genetic study of virulence factors of Actinobacillus pleuropneumoniae. Purification of major toxins, cloning, toxicity on polymorph nuclear neutrophils and macrophages, construction of derivative strains deleted for their virulence genes, protective antigens, elaboration of concepts for live vaccines. b)Genetic and antigenic investigations on Mycoplasma hyopneumoniae and Mycoplasma conjunctivae: Molecular epidemiological methods, Sensitive diagnostics and disease control. c)Mycoplasma mycoides subsp. mycoides SC: Adhesion, mechanisms of virulence, specific antigens. Impact of metabolic pathway products in virulence. d)Virulence factors and epidemiological markers of ruminants Mycoplasmas. e)Type III secretion systems and effector proteins of inflammatory processes in Aeromonas salmonicida and other fish pathogenic Aeromonas species f)Clostridium chauvoei and Clostridium septicum: analysis of major virulence factors. g)Gene probes for the detection of bacterial virulence factors and antibiotic resistance (Bio-safety assessment). h)Recombinant vaccine against botulism i)Molecular typing of Bacillus anthracis and Francisella tularensis 03/02/2021 European Medicines Agency Page 1/26 September 1981-April 1987 Research Assistant Université de Genève (Switzerland) Development of molecular genetic tools for the genetic modification of Pseudomonas and Erwinia and species. Molecular mechanisms or control of plasmid replication October 1980-August 1981 Post doctoral researcher Max Planck Institut für Molekulare Genetik, Berlin (Germany) Control of DNA replication September 2009- Present Professor Bern University of Applied Sciences (Switzerland) Lectures Applied Health Technologies: Molecular Genetics, Infectious diseases EDUCATION AND TRAINING September 1975-September 1980 PhD Université de Genève (Switzerland) Molecular Biology, Biochemistry, Microbiology Thesis topic: Role of the dnaA gene in the control of replication of chromosomal and plasmid DNA. October 1973-June 1975 Diploma in Chemistry and Biochemistry Uppsala University (Sweden) Basic chemistry and biochemistry, Diploma Work (Master thesis): Purification and characterization of human thyroidea stimulating hormone and precursors of groth hormone from human pituitary glands. ADDITIONAL INFORMATION Expertise Veterinary Bacteriology Molecular Biology Biosafety (Member of the Swiss Federal Commission for Biological Safety, EFBS 2003 - 2015) Antibiotic resistance Research topics Molecular mechanisms of bacterial virulence, Infection and inflammation; Microbiology; Genetics and Biochemistry; Vaccine development; Gene array technologies; Bacterial protein toxins, Adhesins and immunogenic factors; Bacteria-host interactions in pathogenesis; Biological safety aspects of natural and genetically modified organisms. The research topics involve: Biochemical and genetic study of virulence factors of Actinobacillus pleuropneumoniae, Clostridium chauvoei, Avibacterium paragallinarum, Dichelobacter nodosus, Actinobacillls equuli, Aeromonas salmonicida, Aeromonas hydrophila. Purification of major toxins, cloning, toxicity on polymorph nuclear neutrophils and macrophages, construction of derivative strains deleted for their virulence genes, protective antigens, elaboration of concepts for live vaccines. Publications Peer reviewed publications Chandler, M., Silver, L., Frey, J. and Caro, L. (1977). Suppression of an Escherichia coli dnaA mutation by the integrated R factor R100.1: Generation of small plasmids after integration. J. Bacteriol. 130: 303-311. Frey, J., Chandler, M. and Caro, L. (1979). The effects of an Escherichia coli dnaAts mutation on the replication of the plasmids ColEl, pSC101, R100.1 and RTF-Tc. Molec. Gen. Genet. 174: 117-126. Frey, J., Chandler, M. and Caro, L. (1981). The initiation of chromosome replication in a dnaAts46 and a dnaA+ strain at various temperatures. Molec. Gen. Genet. 182: 364-366. Bagdasarian, M., Lurz, B.R., Rückert, G., Franklin, F.C.H., Bagdasarian, M.M., Frey, J. and Timmis, K.N. (1981). Specific purpose plasmid cloning vectors, and a host vector system for gene cloning in Pseudomonas. Gene 16: 237-247. Frey, J., Bagdasarian, M., Feiss, D., Franklin, F.C.H. and Deshusses, J. (1983). Stable cosmid vectors that enable the introduction of cloned fragments into a wide range of Gram-negative bacteria. Gene 24: 299-308. Brady, G., Frey, J., Danbara, H. and Timmis, K.N. (1983). Replication control mutations of plasmid R6-5 and their effects on interactions of the RNA-I control element with its target. J. Bacteriol. 154: 429-436. 03/02/2021 European Medicines Agency Page 2/26 Frey, J., Chandler, M. and Caro, L. (1984). Overinitiation of chromosome and plasmid replication in a dnaAcos mutant of Escherichia coli K12: Evidence for DnaA-DnaB interactions. J. Mol. Biol. 179: 171-183. Frey, J., Franklin, F.C.H. and Deshusses, J. (1985). Cloning of the catechol 2,3-oxygenase gene using high- and low-copy number expression vectors. Biochemical Educ. 13: 27-31. Gauchat-Feiss, D., Frey, J., Belet, M. and Deshusses, J. (1985). Cloning of the genes involved in the myo-inositol transport in a Pseudomonas species. J. Bacteriol. 162: 324-327. Frey, J. and Timmis, K.N. (1985). ColD-derived cloning vectors that autoamplify in the stationary phase of growth. Gene 35: 103-111. Frey, J. and Krisch, H.M. (1985). Omega mutagenesis in Gram-negative bacteria: a selectable DNA fragment which is strongly polar in a wide range of bacterial species. Gene 36: 143-150. Haring, V., Scholz, P., Scherzinger, E., Frey, J., Derbyshire, K., Hatfull, G., Willets, N.S., and Bagdasarian, M. (1985). Protein RepC is involved in copy number control of the broad host range plasmid RSF1010. Proc. Natl. Acad. Sci. U.S.A. 82: 6090-6094. Frey, J., Ghersa, P., Palacios, P.G. and Belet, M. (1986). A physical and genetic analysis of the ColD plasmid. J. Bacteriol. 166: 15-19. Frey, J. and Belet, M. (1986). Mobilizable Cloning Vectors Derived from ColD: Their Use in Erwinia. Symbiosis 2: 331-335. Fellay, R., Frey, J. and Krisch, H. (1987). Interposon Mutagenesis of soil and water bacteria: a family of DNA fragments designed for in vitro insertional mutagenesis of Gram-negative bacteria. Gene 52: 147-154. Frey, J., Mudd, E.A., and Krisch, H.M. (1988). A bacteriophage T4 expression cassette that functions efficiently in a wide range of Gram-negative bacteria. Gene 62: 237-247. Piffaretti, J.-Cl., Arini, A. and Frey, J. (1988). pUB307 mobilizes resistance plasmids from Escherichia coli into Neisseria gonorrhoeae. Mol. Gen. Genet. 212: 215-218. Ghersa, P., Lurz, R., Dobrinski, B., Deshusses, J., Belet, M., and Frey, J. (1988). Genetic evidence for the existence of a repressor that modulates colicin D expression on plasmid ColD-CA23. Mol. Gen. Genet. 213: 36-41. Frey, J.