Systems of Lifesystems biology

Database services

• Contribution to:– WP5: Knowledge database

• Database development at DKFZ

– WP3: Manual curation• Modelling of apoptosis and autophagy pathways

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

Application services

RMI

Base2Base2

SpringHibernate

BusinessLayer

PersistenceLayer

DataAccessObjects

DB

Spring Xdoclet

RemoteClient

Interface

RemoteServer

Interface

DomainObjectModel

impl

api

Administration Tool

secretory pathway

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

• Contribution to:– WP3: Manual curation of programmed cell

death ontology

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.

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

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

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