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 Forschungsbericht für das Jahr 2000

Institut für Molekulare Medizin und Zellforschung (IMMZ)

Zentrum für Biochemie und Molekulare Zellforschung (ZBMZ)

Stefan-Meier-Str. 17
79104 Freiburg i. Br.
Tel: +49-761-203-9600/9601 Fax: +49-761-203-9602
Email christoph.peters@mol-med.uni-freiburg.de
http://www.mol-med.uni-freiburg.de


Wissenschaftliche Mitarbeiterinnen und Mitarbeiter

  • Prof. Dr. Christoph Peters, Institutsleiter
  • Prof. Dr. Wolfgang Bessler, Gruppenleiter
  • Prof. Dr. Dr. h.c. Christoph Borner, Gruppenleiter
  • Prof. Dr. Gerhard Konermann
  • Prof. Dr. Friedrich Siebert, Gruppenleiter
  • Prof. Dr. Thomas Dandekar
  • Dr. Jan Deussing
  • Priv. Doz. Dr. Karim Fahmy
  • Dr. Christof von Kalle
  • Dr. Walter Prütz
  • Dr. Mohamed Ayoub
  • Dr. Denis Grandgirard
  • Dr. Sigrid Messemer
  • Dr. Elena Ninci
  • Dr. Hagai Offer
  • Dr. Thomas Reinheckel, Gruppenleiter
  • Dr. Oliver Strauch
  • Dr. Maria Huber, AG Bessler
  • Dr. Klaus Mittenbühler, AG Bessler
Einträge in der Rubrik "Who is Who"

Forschungsschwerpunkte

  • Forschungsschwerpunkte am Institut für Molekulare Medizin und Zellforschung sind die Funktion von Cystein-Proteasen, die Therapie lysosomaler Speicherkrankheiten und die molekularen Mechanismen der Apoptose. Dazu wird ein breites Spektrum moderner Genomfunktionsanalysetechniken eingesetzt. (Gene Knockouts und functional genomics, AG Peters; Proteomics, AG Reinheckel; Bioinformatik, AG Dandekar; Zellbiologie, AG Borner; Gentherapie, AG v. Kalle; biophysikalische Methoden, AG Siebert; Tumorimmunologie, Vakzine, AG Bessler)

Finanzierung

  • BMBF, Gentherapie 2000. 01 KV 9917. "Versuche zur somatischen Gentherapie an Arylsulfatase B defizienten Mäusen, als Modell einer lysosomalen Speicherkrankheit mit nicht neurologischer Symptomatik". (Peters)
  • BMBF. Deutsches Humangenomprojekt, 01 KW 9926/3. "Lysosomal Enzyme Screen" im "ENU-Mouse-Mutagenesis Screen". (Peters)
  • DFB, SFB 388. "Zelluläre Funktionen dynamischer Proteinwechselwirkungen" (Bessler)
  • DFG, SFB 364. "Untersuchungen zum Einfluß lysosomaler Cystein-Proteinasen auf Tumorinvasion und -metastasierung". (Peters)
  • Nationalfonds Schweiz. "Identification of the mode of action of Bcl-2 family members". (Borner)

Wissenschaftliche Projekte und Forschungsvorhaben


  • "Identification of the mode of action of Bcl-2 family members"
    • Projektleitung: Prof. Dr. Christoph Borner
    • Laufzeit: 01.08.2000 bis 31.07.2003
    • Details zum Projekt
  • "Klonalitätsuntersuchungen humaner hämatopoietischer Stammzellen"
  • "Lysosomal Enzyme Screen" im "ENU-Mouse-Mutagenesis Screen"
    • Projektleitung: Prof. Dr. Christoph Peters
    • Laufzeit: 01.01.1999 bis 30.06.2004
    • Details zum Projekt
  • "Retrovirale Gentherapie humaner hämatopoietischer Stammzellen"
    • Projektleitung: Dr. Christoph von Kalle
    • Laufzeit: 01.04.1999 bis 31.03.2003
    • Details zum Projekt
  • "Untersuchungen zum Einfluß lysosomaler Cystein-Proteinasen auf Tumorinvasion und -metastasierung"
  • "Versuche zur somatischen Gentherapie an Arylsulfatase B defizienten Mäusen, als Modell einer lysosomalen Speicherkrankheit mit nicht neurologischer Symptomatik"
    • Projektleitung: Prof. Dr. Christoph Peters
    • Laufzeit: 01.01.1999 bis 31.05.2003
    • Details zum Projekt
  • "Zelluläre Funktionen dynamischer Proteinwechselwirkungen"

Wissenschaftliche Publikationen

Originalarbeiten in wissenschaftlichen Fachzeitschriften:
  • Ayoub M, Mittenbühler K, Sütterlin BW, Bessler WG: The anti-allergic drug histaglobin inhibits NF-kappaB nuclear translocation and down-regulates proinflammatory cytokines Int J Immunopharmaco, 2000; 22 (10): 755-763.
  • Baier W, Loleit M, Fischer B, Jung G, Neumann U, Weiss M, Weckesser J, Hoffmann P, Bessler WG, Mittenbühler K: Generation of antibodies directed against the low-immunogenic peptide-toxins microcystin-LR/RR and nodularin. Int J Immunopharmaco, 2000; 22 (5): 339-353.
  • Baier W, Masihi N, Huber M, Hoffmann P, Bessler WG: Lipopeptides as immunoadjuvants and immunostimulants in mucosal immunization. Immunobiology, 2000; 201 (3-4): 391-405.
  • Botchkareva NV, Botchkarev VA, Welker P, Airaksinen M, Roth W, Suvanto P, Muller-Rover S, Hadshiew IM, Peters C, Paus R: New roles for glial cell line-derived neurotrophic factor and neurturin: involvement in hair cycle control. Am J Pathol, 2000; 156 (3): 1041-1053. : http://www.amjpathol.org/cgi/content/abstract/156/3/1041
  • Brummer T, Engelmann L, Kochs M, V Rooijen H, Hombach V, Binner L: [Not Available]. Herzschrittmacherther Elektrophysiol, 2000; 11 Suppl 1: 115-116. : http://dx.doi.org/10.1007/BF03042554
  • Conus S, Kaufmann T, Fellay I, Otter I, Rosse T, Borner C: Bcl-2 is a monomeric protein: prevention of homodimerization by structural constraints. EMBO J, 2000; 19 (7): 1534-1544.
  • Conus S, Kaufmann T, Fellay I, Otter I, Rosse T, Borner C: Bcl-2 is a monomeric protein: prevention of homodimerization by structural constraints. Embo J, 2000; 19 (7): 1534-1544. : http://dx.doi.org/10.1093/emboj/19.7.1534
  • Conus S, Rosse T, Borner C: Failure of Bcl-2 family members to interact with Apaf-1 in normal and apoptotic cells. Cell Death Differ, 2000; 7 (10): 947-954. : http://dx.doi.org/10.1038/sj.cdd.4400729
  • Conus S, Rossé T, Borner C: Failure of Bcl-2 family members to interact with Apaf-1 in normal and apoptotic cells. Cell Death Differ, 2000; 7 (10): 947-954. : http://www.stockton-press.co.uk/server-java/Propub/stockton/spcdd_v7_n10_p947_o1.abstract
  • Dandekar T, Huynen M, Regula JT, Ueberle B, Zimmermann CU, Andrade MA, Doerks T, Sanchez-Pulido L, Snel B, Suyama M, Yuan YP, Herrmann R, Bork P: Re-annotating the mycoplasma pneumoniae genome sequence: adding value, function and reading frames. Nucleic Acids Res, 2000; 28 (17): 3278-3288. : http://nar.oupjournals.org/cgi/content/abstract/28/17/3278
  • Deussing J, Tisljar K, Papazoglou A, Peters C: Mouse cathepsin F: cDNA cloning, genomic organization and chromosomal assignment of the gene. Gene, 2000; 251 (2): 165-173.
  • Deussing J, von Olshausen I, Peters C: Murine and human cathepsin Z: cDNA-cloning, characterization of the genes and chromosomal localization. Biochim Biophys Acta, 2000; 1491 (1-3): 93-106.
  • Erhard MH, Schmidt P, Zinsmeister P, Hofmann A, Münster U, Kaspers B, Wiesmüller KH, Bessler WG, Stangassinger M: Adjuvant effects of various lipopeptides and interferon-gamma on the humoral immune response of chickens. Poultry Sci, 2000; 79 (9): 1264-1270.
  • Fahmy K, Sakmar TP, Siebert F: Transducin-dependent protonation of glutamic acid 134 in rhodopsin. Biochemistry, 2000; 39 (34): 10607-10612.
  • Fahmy K, Sakmar TP, Siebert F: Structural determinants of active state conformation of rhodopsin: molecular biophysics approaches. Method Enzymol, 2000; 315: 178-196.
  • Foerstendorf H, Lamparter T, Hughes J, Gartner W, Siebert F: The photoreactions of recombinant phytochrome from the cyanobacterium Synechocystis: a low-temperature UV-Vis and FT-IR spectroscopic study. Photochem Photobiol, 2000; 71 (5): 655-661.
  • Foyouzi-Youssefi R, Arnaudeau S, Borner C, Kelley WL, Tschopp J, Lew DP, Demaurex N, Krause KH: Bcl-2 decreases the free Ca2+ concentration within the endoplasmic reticulum. P Natl Acad Sci Usa, 2000; 97 (11): 5723-5728.
  • Foyouzi-Youssefi R, Arnaudeau S, Borner C, Kelley WL, Tschopp J, Lew DP, Demaurex N, Krause KH: Bcl-2 decreases the free Ca2+ concentration within the endoplasmic reticulum. P Natl Acad Sci Usa, 2000; 97 (11): 5723-5728.
  • Geissler E, Hecht AM, Rochas C, Bley F, Livet F, Sutton M: Aging in a filled polymer: coherent small angle x-ray and light scattering Phys Rev E, 2000; 62 (6 Pt B): 8308-8313.
  • Guicciardi ME, Deussing J, Miyoshi H, Bronk SF, Svingen PA, Peters C, Kaufmann SH, Gores GJ: Cathepsin B contributes to TNF-alpha-mediated hepatocyte apoptosis by promoting mitochondrial release of cytochrome c. J Clin Invest, 2000; 106 (9): 1127-1137. : http://www.jci.org/cgi/content/abstract/106/9/1127
  • Hacki J, Egger L, Monney L, Conus S, Rosse T, Fellay I, Borner C: Apoptotic crosstalk between the endoplasmic reticulum and mitochondria controlled by Bcl-2. Oncogene, 2000; 19 (19): 2286-2295.
  • Hacki J, Egger L, Monney L, Conus S, Rosse T, Fellay I, Borner C: Apoptotic crosstalk between the endoplasmic reticulum and mitochondria controlled by Bcl-2. Oncogene, 2000; 19 (19): 2286-2295. : http://dx.doi.org/10.1038/sj.onc.1203592
  • Halangk W, Lerch MM, Brandt-Nedelev B, Roth W, Ruthenbuerger M, Reinheckel T, Domschke W, Lippert H, Peters C, Deussing J: Role of cathepsin B in intracellular trypsinogen activation and the onset of acute pancreatitis. Journal of Clinical Investigation, 2000; 106 ((6)): 773-781.
  • Hecht A, Kemler R: Curbing the nuclear activities of beta-catenin. Control over Wnt target gene expression. Embo Rep, 2000; 1 (1): 24-28. : http://dx.doi.org/10.1093/embo-reports/kvd012
  • Hecht A, Vleminckx K, Stemmler MP, van Roy F, Kemler R: The p300/CBP acetyltransferases function as transcriptional coactivators of Embo J, 2000; 19 (8): 1839-1850. : http://dx.doi.org/10.1093/emboj/19.8.1839
  • Heinrich M, Wickel M, Winoto-Morbach S, Schneider-Brachert W, Weber T, Brunner J, Saftig P, Peters C, Kronke M, Schutze S: Ceramide as an activator lipid of cathepsin D. Adv Exp Med Biol, 2000; 477: 305-315.
  • Hrabe de Angelis MH, Flaswinkel H, Fuchs H, Rathkolb B, Soewarto D, Marschall S, Heffner S, Pargent W, Wuensch K, Jung M, Reis A, Richter T, Alessandrini F, Jakob T, Fuchs E, Kolb H, Kremmer E, Schaeble K, Rollinski B, Roscher A, Peters C, Meitinger T, Strom T, Steckler T, Holsboer F, Klopstock T, Gekeler F, Schindewolf C, Jung T, Avraham K, Behrendt H, Ring J, Zimmer A, Schughart K, Pfeffer K, Wolf E, Balling R: Genome-wide, large-scale production of mutant mice by ENU mutagenesis. Nat Genet, 2000; 25 (4): 444-447. : http://www.nature.com/cgi-taf/DynaPage.taf?file=/ng/journal/v25/n4/abs/ng0800_444.html
  • Huber M, Ayoub M, Pfannes SD, Mittenbühler K, Weis K, Bessler WG, Baier W: Immunostimulatory activity of the bacterial extract OM-8. Eur J Med Res, 2000; 5 (3): 101-109.
  • Huber M, Baier W, Serr A, Bessler WG: Immunogenicity of an E. coli extract after oral or intraperitoneal administration: induction of antibodies against pathogenic bacterial strains. Int J Immunopharmaco, 2000; 22 (1): 57-68.
  • Huber M, Krauter K, Winkelmann G, Bauer HW, Rahlfs VW, Lauener PA, BleBmann GS, Bessler WG: Immunostimulation by bacterial components: II. Efficacy studies and Int J Immunopharmaco, 2000; 22 (12): 1103-1111.
  • Isele J, Sakmar TP, Siebert F: Rhodopsin activation affects the environment of specific neighboring phospholipids: An FTIR spectroscopic study Biophys J, 2000; 79 (6): 3063-3071.
  • Kenealy MR, Flouriot G, Sonntag-Buck V, Dandekar T, Brand H, Gannon F: The 3'-untranslated region of the human estrogen receptor alpha gene mediates rapid messenger ribonucleic acid turnover. Endocrinology, 2000; 141 (8): 2805-2813.
  • Koike M, Nakanishi H, Saftig P, Ezaki J, Isahara K, Ohsawa Y, Schulz-Schaeffer W, Watanabe T, Waguri S, Kametaka S, Shibata M, Yamamoto K, Kominami E, Peters C, von Figura K, Uchiyama Y: Cathepsin D deficiency induces lysosomal storage with ceroid lipofuscin in mouse CNS neurons. J Neurosci, 2000; 20 (18): 6898-6906. : http://www.jneurosci.org/cgi/content/abstract/20/18/6898
  • Marin EP, Krishna AG, Zvyaga TA, Isele J, Siebert F, Sakmar TP: The amino terminus of the fourth cytoplasmic loop of rhodopsin modulates rhodopsin-transducin interaction. J Biol Chem, 2000; 275 (3): 1930-1936.
  • Moin K, Demchik L, Mai J, Duessing J, Peters C, Sloane BF: Observing proteases in living cells. Adv Exp Med Biol, 2000; 477: 391-401.
  • Pross M, Manger T, Reinheckel T, Mirow L, Kunz D, Lippert H: Endoscopic treatment of clinically symptomatic leaks of thoracic esophageal anastomoses. Gastrointestinal Endoscopy, 2000; 51 ((1)): 73-76.
  • Pross M, Schulz HU, Flechsig A, Manger T, Halangk W, Augustin W, Lippert H, Reinheckel T: Oxidative stress in lung tissue induced by CO(2) pneumoperitoneum in the rat. Surg Endosc-ultras, 2000; 14 (12): 1180-1184.
  • Prutz WA, Kissner R, Koppenol WH, Ruegger H: On the irreversible destruction of reduced nicotinamide nucleotides by hypohalous acids. Arch Biochem Biophys, 2000; 380 (1): 181-191.
  • Puscas I, Coltau M, Gilau L, Baican M, Pasca R, Domuta G, Hecht A: The mechanism of action of angiotensin II is dependent on direct activation of vascular smooth muscle carbonic anhydrase I. Int J Clin Lab Res, 2000; 30 (3): 119-125.
  • Puscas I, Gilau L, Coltau M, Pasca R, Domuta G, Baican M, Hecht A: Hypotensive effect of calcium channel blockers is parallel with carbonic anhydrase I inhibition. Clin Pharmacol Ther, 2000; 68 (4): 443-449. : http://dx.doi.org/10.1067/mcp.2000.110559
  • Puscas L, Gilau L, Coltau M, Pasca R, Domuta G, Baican M, Hecht A: Calcium channel blockers reduce blood pressure in part by inhibiting vascular smooth muscle carbonic anhydrase I. Cardiovasc Drug Ther, 2000; 14 (5): 523-528.
  • Reinheckel T, Korn S, Mohring S, Augustin W, Halangk W, Schild L: Adaptation of protein carbonyl detection to the requirements of proteome analysis demonstrated for hypoxia/reoxygenation in isolated rat liver mitochondria. Arch Biochem Biophys, 2000; 376 ((1)): 59-65.
  • Reinheckel T, Ullrich O, Sitte N, Grune T: Differential impairment of 20S and 26S proteasome activities in human hematopoietic K562 cells during oxidative stress. Arch Biochem Biophys, 2000; 377 ((1)): 65-68.
  • Roth W, Deussing J, Botchkarev VA, Pauly-Evers M, Saftig P, Hafner A, Schmidt P, Schmahl W, Scherer J, Anton-Lamprecht I, Von Figura K, Paus R, Peters C: Cathepsin L deficiency as molecular defect of furless: hyperproliferation of keratinocytes and pertubation of hair follicle cycling. FASEB J, 2000; 14 (13): 2075-2086. : http://www.fasebj.org/cgi/content/abstract/14/13/2075
  • Schuster S, Fell DA, Dandekar T: A general definition of metabolic pathways useful for systematic organization and analysis of complex metabolic networks. Nat Biotechnol, 2000; 18 (3): 326-332. : http://www.nature.com/cgi-taf/DynaPage.taf?file=/nbt/journal/v18/n3/abs/nbt0300_326.html
  • Tatnell PJ, Cook M, Peters C, Kay J: Molecular organization, expression and chromosomal localization of the mouse pronapsin gene. Eur J Biochem, 2000; 267 (23): 6921-6930.
  • Tribble G, Ahn YT, Lee J, Dandekar T, Jayaram M: DNA recognition, strand selectivity, and cleavage mode during integrase family site-specific recombination. J Biol Chem, 2000; 275 (29): 22255-22267. : http://www.jbc.org/cgi/content/abstract/275/29/22255
  • vd Esche U, Ayoub M, Pfannes SD, Müller MR, Huber M, Wiesmüller K, Loop T, Humar M, Fischbach K, Strunkelnberg M, Hoffmann P, Bessler WG, Mittenbühler K: Immunostimulation by bacterial components: I. Activation of macrophages and enhancement of genetic immunization by the lipopeptide P(3)CSK(4). Int J Immunopharmaco, 2000; 22 (12): 1093-1102.
  • Vieira O, Escargueil-Blanc I, Jurgens G, Borner C, Almeida L, Salvayre R, Negre-Salvayre A: Oxidized LDLs alter the activity of the ubiquitin-proteasome pathway: potential role in oxidized LDL-induced apoptosis. FASEB J, 2000; 14 (3): 532-542.
  • Vieira O, Escargueil-Blanc I, Jurgens G, Borner C, Almeida L, Salvayre R, Negre-Salvayre A: Oxidized LDLs alter the activity of the ubiquitin-proteasome pathway: potential role in oxidized LDL-induced apoptosis. Faseb J, 2000; 14 (3): 532-542.
  • Vogel R, Fan GB, Sheves M, Siebert F: The molecular origin of the inhibition of transducin activation in rhodopsin lacking the 9-methyl group of the retinal chromophore: a UV-Vis and FTIR spectroscopic study. Biochemistry, 2000; 39 (30): 8895-8908.
  • Vogel R, Siebert F: Vibrational spectroscopy as a tool for probing protein function Curr Opin Chem Biol, 2000; 4 (5): 518-523.
Rezensionen:
  • Dandekar T: Crystal structures of the membrane-binding C2 domain of human coagulation factor V. Structure of the C2 domain of human factor VIII at 1.5 A resolution; Condensation and commentary. Chemtracts - Biochemistry and Molecular Biology, 2000; 13: 398-401.
  • Schultzberg M, Boulin C, Dandekar T: Stochastic sensing of organic analytes by a pore-forming protein containing a molecular adaptor; Condensation and commentary. Chemtracts - Biochemistry and Molecular Biology, 2000; 13: 198-202.
Buchbeiträge:
  • Bork P, Snel B, Lehmann G, Suyama M, Dandekar T, Lathe W III, Huynen M: Comparative genome analysis: exploiting the context of genes to infer evolution and predict function. In: Sankoff D., Nadeau J.H. (Hrsg.): Comparative Genomics. Kluwer Academic Press, Dordrecht, 2000; 281-294.
  • Pfeiffer T, Dandekar T, Moldenhauer F, Schuster S: Topological analysis of metabolic networks. Application to the metabolism of Mycoplasma pneumoniae. In: Hofmeyer J.-H.S., Rohwer J.M., Snoep J.L. (Hrsg.): Biothermokinetics. Animating the Cellular Map. Stellenbosch University Press, Stellenbosch, 2000; 229-234.
  • Reinheckel T, Grune T, Davies KJ: The measurement of protein degradation in response to oxidative stress. In: Keyse, Stephen M. (Hrsg.): Stress Response. Methods and Protocols. Humana Press, Totowa, 2000; 49-60.
Konferenzbeiträge:
  • Mittenbühler K, vd Esche U, Pfannes SDC, Baier W, Müller M, Loop T, Humar M, Weckesser J, Bessler WG: Generation of Antibodies Against Bacterial Toxins by Conventional and Genetic Immunization: Enhancement of the Immune Response by Lipopeptide Adjuvants 2000 (Abstracts of the Biological Medical Defence Conference, Munich).
Sonstige Publikationen:
  • König R, Dandekar T: Neuartige selektive Beschichtungsmethode für die Oberflächenbehandlung (z.B. von Sensoren und Leiterplatinen). Offenlegungsschrift DE 198 33 683 A1, Bundesdruckerei 12.99 902 065/204/1 2000.

Besondere wissenschaftliche Aktivitäten

Abschlussarbeiten

Diplomarbeiten
  • Sanz, Javier: Bcl-2 and Bcl-xL: really the same? (Erstgutachter/in Prof. Dr. Christoph Borner, Zweitgutachter/in N.N.), 2000.
  • Tapernoux, Myriam: Caspase-dependent and -independent regulation of apoptosis. (Erstgutachter/in Prof. Dr. Christoph Borner, Zweitgutachter/in N.N.), 2000.