Prof. Dr. Kay Ohlendieck
Department of Biology, National University of Ireland, Maynooth
Abnormal calcium handling in
muscular dystrophy
Mo 22.
Dezember 2003 ---
17:15 ---
Raum W0-135 (K)
Although the primary deficiency in dystrophin and
the concomitant reduction in surface glycoproteins are well established
factors in the molecular pathogenesis of Duchenne muscular dystrophy,
the pathophysiological events that render a muscle fibre more
susceptible to necrosis are not well understood. One proposed mechanism
involves abnormal calcium homeostasis in mechanically stressed fibres
that eventually leads to skeletal muscle weakness. This seminar examines
the calcium hypothesis of muscular dystrophy and outlines how unbalanced
ion cycling through the sarcolemma and the sarcoplasmic reticulum may
contribute to enhanced degradation of muscle proteins. Studying calcium
handling in muscular dystrophy is not only important for increasing our
knowledge on the multifaceted process of muscle degeneration, but might
also have implications for the future design of therapeutic approaches
to treating X-linked muscular dystrophy. In this respect, it is
encouraging that the pharmacological elimination of Ca2+-dependent
proteolysis counteracts dystrophic changes and that the removal of
excess cytosolic Ca2+ appears to convey natural protection to
dystrophin-deficient fibres.
Gastgeber: H. Jockusch
Prof. Dr. Klaus Willecke
Institut für Genetik, Rheinische Friedrich-Wilhelms-Universität, Bonn
Biological function of gap
junction proteins in the mouse
Mo 15.
Dezember 2003 ---
17:15 ---
Raum W0-135 (K)
Gap junction channels between mammalian cells are
formed by docking of two hemichannels each of which comprises 6 protein
subunits, the connexins. Twenty different connexin genes in the mouse
genome are cell-type specifically expressed with overlapping
specificity. Many of these genes have been generally or conditionally
deleted and replaced by a reporter gene in the mouse genome.
After an overview on the connexin gene family in mouse and man, recent
results will be presented regarding the function of different connexin
genes in cardiac and neural tissues. We are beginning to understand the
functional diversity of connexin genes.
Supported by a travel grant from the DAAD
Gastgeber: H. Jockusch
Prof. Dr. Jochen Graw
GSF Institute Developmental Genetics, München
The Importance of Mouse
Mutants in Understanding of Eye Development
Fre 21.
November
2003 --- 12:15 ---
Raum V7 140/144 (S)
The mature eye is a complex organ that develops
through a highly organized process during embryogenesis. Alterations in
its genetic programming can lead to severe disorders that become
apparent at birth or shortly afterwards; for example, one-half of cases
of blindness in children have a genetic cause. The genetic basis of the
eye development, as determined by mutation analysis in human patients
and animal models, will be outlined. Especially mouse mutants with
defects in the genes Pax6, Pitx3, CrygA-F, and Fgf10 led to a better
understanding of how this intricate organ develops.
Gastgeber: T.
Schmitt-John
Prof. Dr. Anna Starzinski-Powitz
Humangenetik für Biologen, Goethe-Universität, Frankfurt/M.
Cadherin-interacting proteins
and the connection to cytokine-mediated signals.
Mo 17. November
2003 --- 17:15 ---
Raum W0-135 (K)
Generally, we are interested in proteins whose
function is connected to the morphoregulatory activity of cadherins and
which interact, either directly or indirectly, with this class of
adhesion proteins. One of the cadherin-binding proteins is ARVCF
belonging to the p120(ctn) subfamily of catenins. We have studied the
regulation of ARVCF's attenuation of cadherin-binding by the cytokines
TNFalpha and EGF as well as PMA and characterised the
cytokine-responsive element in ARVCF by gain-of-function' experiments.
These results possibly reflect a signalling function of ARVCF in
cytokine-regulated processes. Furthermore, we investigate the structure
and function of a novel integral membrane protein, shrew-1. This protein
is found in vertebrates but not in Drosophila, celegans or yeast and
does not seem to be part of a multigene family. Shrew-1 is able to
target to cadherin-mediated adherens junctions in polarised epithelial
cells where it interacts with the cadherin-catenin complex. Experiments
are in progress to evaluate the potential function and regulation of
shrew-1 in the dynamics of cadherin-mediated junctions.
Gastgeber: H.
Jockusch
Prof. Dr. Takeshi Tsubata
Dept. of Immunology, Medical & Dental University, Tokyo
Regulation of B lymphocyte
activation by inhibitory BCR
co-receptors CD22 and CD72
Di
11. November
2003 --- 16:15 ---
Raum W0-135 (K)
The quantity and quality of signal output from
the B cell antigen receptor (BCR) is modulated by inhibitory receptors
such as CD22 and CD72. This negative regulatory feedback loop involves
the protein tyrosine phosphatase SHP-1 which is recruited to the
phosphorylated immunoreceptor tyrosine-based inhibitory motif (ITIM) in
the cytoplasmic tails of CD22 and CD72. By dephosphorylating BCR
effector proteins, such as SLP-65, SHP-1 then contributes to signal
termination. The group of Prof. Tsubata recently found that this control
mechanism is employed in an isotype-specific manner. Despite the large
progress in identifying more and more of the BCR effector molecules
during the last decade, the understanding of intracellular signaling
networks under various immunological conditions remains a challenge. It
is, however, likely that we will be able to learn from pathogens such as
the B-lymphotropic Epstein-Barr Virus (EBV) which "knows" exactly how to
reorganize SLP-65 effector molecules in order to establish a delicate
signaling balance between activation and repression of specific pathways
which finally allows a latent persistence of the virus.
Gastgeber: J. Wienands
Dr. Harald Neumann
Neuroimmunology, European Neuroscience Institute Göttingen
Molecular mechanism and
therapy of inflammatory neuronal damage
Mo 10. November
2003 --- 17:15 ---
Raum W0-135 (K)
Cytotoxic T lymphocytes (CTLs) with a CD8
phenotype have the potential to recognize and attack major
histocompatibility complex (MHC) class I-expressing brain cells. Most
brain cells, including neurons, can be stimulated to present peptides to
CD8+ CTLs by MHC class I molecules, and are susceptible to CTL-mediated
cytotoxicity in culture. In disease-affected brain parenchyma, CD8+ CTLs
outnumber other T-cell subtypes. They show clonal expansion in several
inflammatory and degenerative CNS diseases, such as multiple sclerosis
(MS), virus-induced inflammatory brain diseases and paraneoplastic
neurological disorders. In MS, damage of axons is closely linked to the
CD8+ CTLs, and protection against CTL-mediated damage should be
considered as a new therapeutic approach in MS and other
neuroinflammatory diseases.
Gastgeber: J.W.
Bartsch
Dr. Marcia Moss
Biozyme, APEX, North Carolina, USA
Beyond TNF alpha converting
enyme: In search of other ADAM family sheddases as targets for drug
discovery.
Mo 3. November
2003 --- 17:15 ---
Raum W0-135 (K)
TNF alpha converting enyzme or TACE is an enyme
of the ADAM family of proteases (a disintegrin and metalloproteainase).
TACE was purified based on its ability to process the inflammatory
cytokine, TNF alpha. Therefore, inhibitors of this metalloproteainase
could be beneficial in the treatment of arthritis. Further investigation
of the substrates for TACE have revealed that it also processes members
of the EGF (epidermal growth factor) ligand family. Since inhibition of
the enzymes responsible for EGF ligand release could be useful for the
treatment of cancer, investigators are beginning to explore whether TACE
inhibitors will work in cancer models. My talk will focus on the
identification of a TGF alpha (transforming growth factor alpha)
processing enzyme that is separate from TACE. In addition we have found
a novel potential function for ADAM 10, and propose that it is important
in allergic responses.
Gastgeber: J.W.
Bartsch
Prof. Dr. Reinhard Wetzker
Universität Jena
Multiple signaling activities of phosphoinositide
3-kinase γ
Dienstag, 219.
Oktober 2003,
15:00 s.t. Raum
W0-135 (S)
Phosphoinositide 3-kinases
(PI3K) represent a group of intracellular signaling proteins involved in
the regulation of diverse cellular responses including proliferation,
differentiation and secretory processes. Four species of PI3K have been
partially characterised so far. Whereas the heterodimeric PI3Kd, b and e
are regulated by receptors with intrinsic or associated tyrosine kinase
activity, PI3Kg reveals sensitivity to agonists of G protein-coupled
receptors. Multiple molecular functions of PI3K have been observed in
vitro. Thus PI3Kg was shown to express lipid kinase and protein kinase
activities. In addition, PI3Kg undergoes various interactions with other
signaling proteins including Gbg, Ras, Raf, MEK and the adapter protein
p101. Transient expression of PI3Kg in COS-7 cells induces stimulation
of the protein kinases Erk, JNK and Akt/PKB. The lipid kinase and
protein kinase activities of PI3Kg are differentially involved in these
signaling events. Whereas PI3Kg protein kinase activity is sufficient
for Erk stimulation, its lipid kinase activity appears to be essential
for the regulation of Akt. The pleiotropic properties of PI3K emerging
in model systems coincide with their functional diversity in vivo.
Recent results on multiple regulatory functions of PI3K3 in leukocytes
unveil a specific regulatory function of PI3Kg in erythroid
differentiation. The data will be discussed with respect to the specific
role of PI3K´s signaling activities observed in vitro and in the COS-7
cell system.
Gastgeber: J. Wienands
Dr. Martin Augustin
Ingenium
Pharmaceuticals AG, Martinsried
Screening the druggable genome
animal models for target validation
Fre 10. Oktober
2003 --- 12:15 ---
Raum W7-135
With completion of the genome sequences of both
humans and mice the research attention is shifting from problems of gene
structure and genome organization to questions of protein function and
interactions, developmental and physiological pathways, and systems
biology. Mouse genetic models have a rich tradition in the elucidation
of molecular pathways underlying abnormalities and diseases in humans.
Many of the genes that have provided insight into mammalian development
and disease were discovered on the basis of the phenotypes of mutant
mice. Currently 10570 alleles and phenotypes are listed in the Mouse
Genome Database representing 4000 individual genes. The fraction of
chemically or genetically engineered mouse alleles is constantly growing
and has reached a number of 4500 (2600 individual genes) in this
database. Mutagenesis with the germline supermutagen ethyl nitrosourea
(ENU) have been carried out in a high-throughput fashion for the
generation of large numbers of new mutants for systematic studies of
mammalian gene function. While this concept is generally accepted for
phenotype-driven screens, there are only a few efforts to use ENU
mutagenesis in gene-driven approaches. We have established an
industrialized technical platform that uses ENU mutagenesis in
conjunction with parallel archives of murine DNA and sperm. The rapid
detection of point mutations in the DNA is followed by/ in vitro
fertilization using the corresponding sperm sample.
Gastgeber: Thomas Schmitt-John
Dr. med. vet. Caroline Johner
Medical Center Central Clinical Research;
Universität Freiburg/Br.
Kryokonservierung oder die Kunst des Überlebens im
flüssigen Eis
Montag, 29. September 2003,
12:15 Raum
W0-135 (S)
Die Kryokonservierung von
Mausgameten bietet vielfältige Anwendungs-möglichkeiten in der
Organisation einer Versuchstierhaltung:
¨ Etablierung von Tierbeständen in neuen Einheiten
¨ Sanierung von infizierten Stämmen
¨ Archivierung
Es soll ein Überblick über die Anwendungsmöglichkeiten sowie der Vor-
und Nachteile der verschiedenen Methoden dargestellt werden.
Gastgeber: A. Ziesenis
Prof. Dr. Thomas Braun
Institut für Physiologische Chemie, Universität Halle
Cells and signals: approaches to reprogramming
cardiac and skeletal muscle
Montag, 7. Juli 2003,
17:15 Raum
W0-135 (K)
Our approaches to contribute to
regenerative medicine are best characterized by two strategies: (i) a
better understanding of processes that lead to proliferation of organ
typical precursor cells and their coordinated differentiation during
organ development and regeneration; (ii) development of pre-clinical
models in which knowledge gained in approach (i) can be used to enable,
improve and accelerate tissue regeneration in particular of the heart.
Individual research projects will be described that are part of this
concept.
Gastgeber: Harald Jockusch
Prof. M. Coletta
Experimental Medicine and Biochemical Sience, University tor Vergata, Rome
Functional Modulation of the Enzyme Activity of MetalloProteinases
Monday, june 30 2003, 17:15;
Raum W0-135 (K)
The investigation has been focussed on the catalytic functional properties of neutrophil collagenase (MMP-8) and gelatinase A (MMP-2), which are able to cleave several components of the extracellular matrix, such as different types of collagen, fibronectin and others. Native MMP-8 cleaves the triple-helical collagen I at a specific site, but the removal of the hemopexin-like carboxy terminal domain brings about a drastic alteration of the cleavage mechanism, which becomes less specific and faster. The gelatinase A is a very important enzyme from the pathological standpoint, since its activation has been correlated to an enhancement of angiogenesis and of diffusive power of tumor cells, resulting a relevant metastatic factor. The study on this enzyme aimed to deepen the enzymatic characterization of such a protein toward some natural substrates, like fibronectin, collagen I and collagen IV. In the case of collagen I, the functional analysis has been addressed towards individual components of this substrate, such as the enzymatic processing of aggregates, (i.e., b-collagen) and of the triple-helical individual molecule (i.e., a-1 and a-2). Therefore, we have compared the catalytic properties of MMP-2 toward all these natural substrates in order to better understand the actual behaviour of this protein in vivo within the extracellular matrix. On both enzymes we have studied the modulation of the catalytic actiuvity by environmental conditions, such as pH.
Gastgeber: H. Tschesche
Dr. Philip Poole
University of Reading, UK
Amino acid cycling drives nitrogen fixation in the
Rhizobium-legume symbiosis
Donnerstag,
26. Juni 2003, 12:15 Raum V 6 - 138 (S)
Most (~65%) of the biosphere's available nitrogen is obtained by biological reduction of abundant, but inert, atmospheric
N2 to ammonium. The majority is contributed by legume-rhizobia symbioses, which are initiated by infection of legume hosts by bacteria (rhizobia), resulting in formation of root nodules. Bacteroids, the nodule form of rhizobia, obtain dicarboxylic acids as a carbon and energy source from the plant, enabling
N2 reduction to ammonium. It had been thought, that in return bacteroids simply provide the plant with ammonium. However, we propose that a more complex amino acid cycle is essential for symbiotic nitrogen fixation in pea nodules. The plant provides amino acids to bacteroids, enabling them to shut down ammonium assimilation. In return, bacteroids effectively act like plant organelles to cycle amino acids back to the plant for asparagine synthesis. The mutual dependence of this exchange prevents the symbiosis being dominated by the plant and provides a key selective pressure for the evolution of mutualism.
Gastgeber: Anke Becker
Dr. Thomas Weimar
Institut für Chemie, Universität Lübeck
Untersuchung biomolekularer Wechselwirkungen mit Hilfe
der NMR-Spektroskopie und der Oberflächen-Plasmonen-Resonanz
Montag, 23. Juni 2003,
17:15 Raum W0-135 (K)
Die Erkennung kleiner Liganden durch Biomakromoleküle spielt eine wichtige Rolle in vielen biologischen Prozessen. Wir untersuchen solche Komplexe mit Hilfe der NMR-Spektroskopie, der Surface Plasmon Resonance (SPR, Oberflächen-Plasmonen-Resonanz) und Kraftfeldrechnungen. Dabei liefert die NMR-Spektroskopie strukturelle, die SPR thermodynamische und kinetische Daten der untersuchten Systeme. Die experimentellen und theoretischen Methoden ergänzen sich hervorragend, so dass man einen verbesserten Einblick in die untersuchten Komplexe erhält. Dies soll an Beispielen aus dem Bereich der Oligosaccharid-Protein- bzw. Aminoglycosid-RNA-Wechselwirkungen dargestellt werden.
Gastgeber: Norbert Sewald
Dr. Andreas Bachmair
MPI Züchtungsforschung, Köln
Protein modification in plants by
ubiquitin and SUMO
Montag, 10. März 2003,
16:15 Raum W0-135 (K)
Proteine können nicht nur durch das Anheften von kleinen Resten wie Phosphat-, Methyl- oder Acetatgruppen in ihren Eigenschaften verändert werden. Auch kleine Proteine, sogenannte Modifikatoren, können nach deren Biosynthese kovalent an Substrate angehängt werden. Der bekannteste "modifier" ist Ubiquitin, das eine wichtige Rolle beim Proteinabbau spielt. Ein anderer Modifikator, SUMO (small ubiquitin-like modifier), ist ebenfalls essentiell. Über seine Rolle im Zellgeschehen ist noch relativ wenig bekannt. Wir untersuchen Ubiquitylierung und SUMOylierung in Pflanzen, Modellsystem ist
Arabidopsis thaliana.
Gastgeber: Harald
Jockusch
Workshop "Signalling
from the ECM to the Nucleus in
Animals and Plants" 20.
& 21. february 2003
Dr. Andreas Lengeling
GBF, Braunschweig
Gone but not forgotten - The clearance of apoptotic cells and the impact on the immune system.
Montag,
13. Januar 2003, 17:15 Uhr
Raum W0-135 (K)
Apoptotic cells are taken up by means of their interaction with phagocyte receptors and specific extracellular signals that are generated during the induction of the apoptotic program.
Depending on the context, the removal of apoptotic cells by phagocytes might suppress inflammation, modulate the macrophage-directed deletion of host cells or invading parasites and critically regulate immune responses.
Several receptors have been implicated in apoptotic cell engulfment and clearance, however, their relative dominance in mammalian systems remains to be established.
In our group we are using different approaches in mouse models to study the in vivo consequences of apoptotic cell clearance and the impact on immune responses and host defence in different bacterial infections models. An update of these experiments will be presented.
Gastgeber: Harald Jockusch, Thomas Schmitt-John
