1. Systems of Life systems biology Database services

2. Contribution to: –WP5: Knowledge database Database development at DKFZ –WP3: Manual curation Modelling of apoptosis and autophagy pathways

3. iCHIP Plattform Collaborations and Partner projects others.... Oracle Database Core Framework Data Management Data Management Application Services Application Services Bio material Data Experiment Data MIAM/P/R/E Web Reporting Data Export Query Tool Web Client Gui Concept

4. Application services RMI Base2 Spring Hibernate Business Layer Persistence Layer Data Access Objects DB Spring Xdoclet Remote Client Interface Remote Server Interface Domain Object Model impl api

5. Administration Tool

6. secretory pathway

8. 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

9. Contribution to: –WP3: Manual curation of programmed cell death ontology

10. Programmed cell death pathways Programmed cell death is the complex result of context- dependent (e.g. cancer, viral infection, ischemia) interactions of apoptotic and autophagic pathway participants.

11. 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

12. 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 calcium signaling Protects against pro-apoptotic Bax, Bak, oxygen radicals. Bcl-xL Bcl-2 FK506 binding protein RTN-xS Binding protein

13. Zooming into the Apoptosis Network Superpositi on of apoptotic pathways CD95 (Fas/APO-1) Receptor FADD Caspases 8,3 IAPs c-FLIP long,short IKK, I  B , NF-  B