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Systems of Lifesystems biology
Database services
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• Contribution to:– WP5: Knowledge database
• Database development at DKFZ
– WP3: Manual curation• Modelling of apoptosis and autophagy pathways
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iCHIP PlattformCollaborations and Partner projects
others....
OracleDatabase
Core FrameworkCore Framework
Data Management
Data Management Application
Services
Application Services
Bio material
DataExperiment
DataMIAM/P/R/E
Web Reporting
Data Export
Query Tool
Web Client GuiWeb Client Gui
Concept
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Application services
RMI
Base2Base2
SpringHibernate
BusinessLayer
PersistenceLayer
DataAccessObjects
DB
Spring Xdoclet
RemoteClient
Interface
RemoteServer
Interface
DomainObjectModel
impl
api
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Administration Tool
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secretory pathway
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10 Mio images
40 Terra Bytes of data
2 whole genome knockout projects
30 studies, 10k Microarrays
10 research networks (incl. 5 EU partners)
iCHIP projects
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• Contribution to:– WP3: Manual curation of programmed cell
death ontology
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Programmed cell death pathways
Cell death
Autophagic PW
Pro-apoptotic PW
Cell death
Cell survivalCell insult
Anti-apoptotic PW
• Programmed cell death is the complex result of context- dependent (e.g. cancer, viral infection, ischemia) interactions of apoptotic and autophagic pathway participants.
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Programmed cell death pathways
• • Apoptosis– Extrinsic (death receptor)– Intrinsic (mitochondrial)
• Autophagy (dual role)– Can protect against apoptosis during ischemic injury)– Can enhance cancer cell death
• Lysosomal (linked to autophagy)– Release of lysosomal cathepsins
• Sufficient to induce cell death• Can activate mitochondrial apoptotic PW
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Sub-cellular localization
• E.g., anti-apoptotic Bcl-xL and Bcl-2 function differently at both mitochondria (Mito) and endoplasmic reticulum (ER)
(Tagami et al, 2000; A novel protein, RTN-xS, interacts with both Bcl-xL and Bcl-2 on endoplasmic reticulum and reduces their anti-apoptotic activity)(Germain & Shore, 2003; Cellular distribution of Bcl-2 family proteins.)
ER Mito
Protects against lethal calciumsignaling
Protects against pro-apoptotic Bax, Bak,oxygen radicals.
Bcl-xL
Bcl-2
FK506 binding protein
RTN-xSBinding protein
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Zooming into the Apoptosis Network
• Superposition of apoptotic pathways
• CD95 (Fas/APO-1) Receptor
• FADD• Caspases 8,3• IAPs
• c-FLIPlong,short
• IKK, IB, NF-B