valapodyn: curing neurodegenerative disease

8/8/2019 Valapodyn: Curing Neurodegenerative Disease

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A European Integrated Project supported through the Sixth Framework Programme for Research and Technological Development

www.valapodyn.eu

Curing Neurodegenerative Disease

valapodyn


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ContextModern high throughput technologies in biological science, such as genomics, transcriptomics and proteo-

mics, oten generate lists o molecules o interest. Yet, this does not necessarily increase our knowledge o

biological or pathological processes and leads to the isolation o non relevant therapeutic targets especially

when multiactorial diseases are studied. This results in a high ailure rate in the development o new drugs and

thereore signicantly contributes to the high and rising cost o drugs. The challenge, thereore, is to construct

a descriptive model rom these lists o molecules that refects the underlying biological mechanisms as accu-

rately as possible, in order to select relevant therapeutic targets.

Systems Biologyworks towards understanding the intricacies o cellular lie through the collaborative eortso biologists, chemists, mathematicians and computer scientists who develop maps o the molecular interac-

tion networks and in some cases dynamic models.

Pathological

stimulus

Nucleus

Protein G

Phosphatase

Transcription

factor

Transporter

Kinase

Kinase

Enzyme

Pathological

stimulus

This approach is emerging also in medicine,

with systems pathology leading to a bet-

ter understanding o the molecular signature

o the disease and systems pharmacology

providing insight into dynamic system res-

ponses upon multiple drug perturbations.

Knowledge o the changes o system cha-

racteristics during disease progression is

absolutely necessary to create a ramework

or the design o novel combinatorial treat-

ment strategies.

To address these needs

and to develop new tools

or therapeutic research,

the participants o the

VALAPODYN (Validated

Predictive Dynamic Mo-

del of Complex Intracel-

lular Pathways Related toCell Death and Survival)

project have created a

network composed o

leading authorities in the

elds o dynamic systems biology, genomics,

proteomics, bioinormatics and neuroscience.

Receptor Regulatory Proteins Effector

Proteomics Facility

Current medications

have symptomatic

actions in neurology

Valapodyn -

pathological action in

complex intracellular

networks


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Strategy

The objective o the VALAPODYN project is to de-

velop a new innovative Systems Biology approach

to model the dynamics of Molecular Interaction

Networks (MIN) related to cell death and survival in

the organism. The uture dynamic model will be de-

dicated to the selection odrug targets for human

brain pathologies such as epilepsy, ischemia, Par-

kinson and Alzheimer.

The project validates dynamic models for neuro-

degeneration through the characterisation o (new)

drug targets in an animal model or epilepsy where

neuronal death is the initial step in the pathological

process.

Changing the paradigm o current biological data

analysis methods, VALAPODYN develops a dyna-

mic and quantitative analysis method to select new

therapeutic targets through MIN dynamic models.

WP1Data

base

systems

& MIN

WP6

ProjectManagement

WP3Dynamic Modeling &

Target Selection

Valapodyn Work Packages

WP4Target Validation

WP5Animal Models &

Pathological Tissues

WP2Protein Analysis &

Gene Expression

sIRNAActive

MIN

targets

Future

Dynamicmodel

validatestherapeuticmolecules

RNA

chips

Protein

analysis

Objectives

To develop a large-scale MIN modelling method that

will allow to rationally address the physiopathology

o several diseases, the VALAPODYN project is

structured into fve interacting modules:

1. A static representation o the biological sys-

tem to be modelled (WP1).2. Experimental measures o the components o

the system (WP2).

3. A mathematical modelling method (WP3).

4. Molecular testing and validation o the mathe-

matical models (WP4).

5. Development o high quality cellular and ani-

mal models (WP5).

The new tools developed to build the dynamic mo-

dels o neurodegeneration processes will constitute

the basis or uture therapeutic research in several

other diseases including cancer, ischaemia, Alzhei-

mer disease and neuromuscular disorders and more

generally or multiactorial diseases.

500 m

Increase of expression of a variant of

acetylcholinesterase in the hippocampus

of mice subjected to acute stress (right)

compared to controls (left).

Cell loss and neuroplasticity observed in

the hippocampus of a mouse model of

mesiotemporal lobe epilepsy (right) com-

pared to controls (left).

500 m


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Project Coordinator:INSERM - Dr Antoine Depaulis: [email protected],

+33 4 76 63 54 14

Dissemination Manager:The Foundation or Biomedical Research o the Academy o Athens

(FBRAA) - Dr Despina Sanoudou: [email protected],

+30 2 1 06 59 74 53

With the support of ALMA Consulting Group:Dr Raaella Catena: [email protected], +33 (0)4 72 35 80 30 C

ration::Comte::www.comete.com

Institut National de la Sant et de la Recherche Mdicale,Grenoble, France /www.inserm.fr

BIOBASE, GmbH,Wolfenbuettel, Germany /www.biobase-international.com

Hlios Biosciences SARL,Crteil, France /www.helios-bioscience.com

Foundation for Biomedical Research, Academy of Athens,Athens, Greece /www.bioacademy.gr

University of Liege, Liege, Belgium /www.ulg.ac.be

Hebrew University of Jerusalem,Jerusalem, Israel /www.huji.ac.il

Alma Consulting Group, Lyon, France /www.almacg.com

Consortium

Acknowledgments

Curing Neurodegenerative Disease

valapodyn

The VALAPODYN project is supported by the Eu-

ropean Commission through the Sixth Research

Framework Programme or Research and Techno-

logical Development (FP6, 2002-2006) at a level o

1,488,649 (or a total budget o 2,145,354 ).

The VALAPODYN project addresses the thematic

area Lie sciences, genomics and biotechnology

or health. The project has been started on 1st Oc-

tober 2006 and will last 36 months.

The VALAPODYN consortium consists o 7 par-

tners, coming rom 5 European countries. It gathers

many years o research in dierent elds such as

genomics (FBRAA), proteomics (ULG), molecular

interactions (HELIOS, BIOBASE), RNA intererence

(HUJI), neuroscience (INSERM), and management

expertise (ALMA).

www.valapodyn.eu

valapodyn: curing neurodegenerative disease

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