SPP 1087:  Selenoproteine - Biochemische Grundlagen und klinische Bedeutung

• Subject Area: Biology
• Term: from 2000 to 2006
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5470054

The priority programme "Selenoproteins - Biochemical Basis and Clinical Aspects" deals with a new peculiar group of proteins, which contain the proteinogenic 21st amino acid selenocysteine as essential component of their active site. The trace element selenium, which is essential for animals and some microorganisms, acts mainly via these selenoproteins. Cotranslational incorporation of selenocysteine occurs in the context of a specific hairpin loop in 3'-position of UGA codons of mRNAs encoding selenoproteins. Special, partly selenium-dependent translation factors and a selenocysteine-charged tRNA are required and prevent chain termination usually programmed by UGA. Analysis of the biosynthesis of the amino acid selenocysteine and its incorporation into selenoproteins is one of the research topics of this interdisciplinary priority programme. A further aim is the resolution of the structures of components involved. Functional characterization of known and new selenoproteins and investigations on the regulation of expression of selenoproteins will reveal information on the biological role of selenium in normal physiology and in pathological conditions and diseases. Between 30 and 50 mammalian selenoproteins are expected to exist. Selenoproteins so far known are involved in antioxidative cellular defense (glutathione peroxidases), regulation of cellular redox state and transcription (thioredoxin reductases), thyroid hormone metabolism (deiodinases), spermatogenesis, and bacterial generation of energy. Selenium status has also been linked to various forms of cancer. The interdisciplinary links between genetics, microbiology, developmental biology, biochemistry, and medicine in the projects of this priority research programme will provide synergisms to advance this exciting field of life sciences.

• DFG Programme: Priority Programmes

Projects

• Algorithmic determination of whether a protein`s cysteine residue can be replaced by selenocysteine by silent/similiar pointwise mutagenesis in DNA/RNA. Intended application to phase determination in X-ray crystallography and NMR spectroscopy. (Applicant Backofen, Rolf )
• Algorithmic determination of whether a protein`s cysteine residue can be replaced by selenocysteine by silent/similiar pointwise mutagenesis in DNA/RNA. Intended application to phase determination in X-ray crystallography and NMR spectroscopy. (Applicant Söhling, Brigitte )
• Analysis of expression regulation of selenoproteins in neurons and Gliazellen (Applicant Savaskan, Nicolai )
• Biological function of selenoprotein P: Binding characteristics and cellular localization (Applicant Sies, Helmut )
• Cellular location, differential regulation and function of selenoproteins in the human thryoid (Applicant Köhrle, Josef )
• Characterization of mice lacking functional phospholipid hydroperoxide glutathione peroxidase (PHGPx): tissue specific gene targeting (Applicant Bornkamm, Georg Wilhelm )
• Charakterization of mice lacking functional mitochondrial thioredoxin reductase (TR2): tissue-specific gene targeting (Applicant Brielmeier, Markus )
• Crystal Structure Analyses of Selenoprotein Biosynthesis (Applicant Wahl, Markus C. )
• Expression regulation of phospholipid hydroperoxide glutathione peroxidase isoforms. Transcriptional and post-transcriptional processes (Applicant Kühn, Hartmut )
• Functional and structural characterization of the Se-Mo active site in CO dehydrogenase (Applicant Meyer, Ortwin )
• Genetics of selenoprotein synthesis in Drosophila melanogaster (Applicant Jäckle, Herbert )
• Human thioredoxin Reductases: Selenoproteins as Potential Drug Targets (Applicant Becker, Katja )
• Identification and characterization of new selenoproteins in the mammalian organism (Applicant Kyriakopoulos, Antonios )
• Mechanism of UGA decoding as selenocystein in Gram-positive anaerobic bacteria (Applicant Andreesen, Jan Remmer )
• Modulation of apoptotic cell death by selenium supplementation (Modulation des apoptotischen Zelltods durch Selen-Supplementierung) (Applicant Wendel, Albrecht )
• Molecular Mechanisms of Selenocysteine incorporation in Bacterial Bakterial Translation (Applicant Rodnina, Marina V. )
• New functions of selenoproteins in Gram-positive, anaerobic bacteria (Neue Funktionen von Selenoproteinen in Gram-positiven, anaeroben Bakterien) (Applicant Andreesen, Jan Remmer )
• Physiological effects of altered Se transport and Se tissue distribution in selenoprotein P knock out mice - studies on the impact of gender on the phenotype (Applicant Schomburg, Lutz )
• Reactivity and modelling studies of Selenium in Se-proteins and reference compounds: Examination and design of Selenium-selective tags and ligands (Applicant Wessjohann, Ludger A. )
• Role of phospholipid hydroperoxide glutathione peroxidase (PHGPx) in sperm maturation (Applicant Flohé, Leopold )
• Selenoprotein biosynthesis in Archaea (Selenoprotein Biosynthese in Archaea) (Applicant Böck, August )
• Selenoproteins - biochemical basis and clinical relevance (Applicant Köhrle, Josef )
• The impact of selenium and selenoproteins on stem cell based bone regeneration and regulation of celcium metabolism (Applicant Jakob, Franz )
• Tissue-specific regulation of the expression on individual glutathione peroxidases (Applicant Brigelius-Flohé, Regina )

• Spokesperson: Professor Dr. Josef Köhrle