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Keywords | Apoptosis | autophagy | necrosis | programmed | cell death |<br />
TransDeath<br />
Programmed Cell Death across<br />
the Eukaryotic Kingdom<br />
Summary<br />
The project aims to broaden the experimental net to catch<br />
regulators of programmed cell death (PCD) by comparative<br />
research on diverse organisms that each may be uniquely<br />
suited to unravel a type of conserved PCD process. The major<br />
approach will be across the eukaryotic kingdom and the<br />
main objective will be to understand these types of cell death<br />
in humans. TransDeath thereby aims to produce knowledge<br />
on genes and biochemical processes that regulate PCD in<br />
diff erent organisms, and to apply that knowledge to develop<br />
strategies and targets for human disease therapy.<br />
Problem<br />
Programmed cell death (PCD) is normally invoked during<br />
development and immunity, but inappropriate PCD is associated<br />
with pathologies, including cancer and degenerative<br />
diseases. Conserved genes controlling apoptosis, a type of<br />
PCD dependent upon caspase proteinases, were fi rst identifi<br />
ed in the model organism C. elegans. This work received<br />
a Nobel Prize in 2003, and biomedical research has established<br />
related mammalian PCD pathways. However, phylogenetically<br />
conserved PCD types other than apoptosis exist in animal<br />
and non-animal cells. This TransDeath project will focus on<br />
cellular and molecular events in these less well-known cell<br />
death types.<br />
Aim<br />
The specifi c TransDeath objectives include:<br />
• characterising the diversity of genes and biochemicals<br />
controlling PCD of diverse types;<br />
• functionally comparing these genes and biochemicals<br />
between organisms;<br />
• deriving genetic and functional models of PCD evolution.<br />
Expected results<br />
The results of this project should be of value to the European<br />
and international scientifi c communities. Our eff orts will<br />
strengthen European research in the strategic area of functional<br />
genomics and yield information on gene function in<br />
PCD immediately relevant to pharmaceutical R&D.<br />
Potential applications<br />
Test genes and biochemicals on PCD related to normal human<br />
function and disease.<br />
Coordinator<br />
John Mundy<br />
University of Copenhagen<br />
Copenhagen, Denmark<br />
mundy@my.molbio.ku.dk<br />
Partners<br />
Kai-Uwe Fröhlich<br />
University of Graz,<br />
Graz, Austria<br />
kai-uwe.froehlich@uni-graz.at<br />
Corinne Clavé<br />
CNRS – UMR 5095<br />
Bordeaux, France<br />
corinne.clave@ibgc.u-bordeaux2.fr<br />
Pierre Goldstein<br />
CNRS – CIML<br />
Marseille, France<br />
golstein@ciml.univ-mrs.fr<br />
Guido Kroemer<br />
CNRS – UMR 8125<br />
Villejuif, France<br />
kroemer@igr.fr<br />
Project number<br />
LSHG-CT-2004-511983<br />
EC contribution<br />
€ 2 500 000<br />
Duration<br />
36 months<br />
Starting date<br />
01/12/2005<br />
Instrument<br />
STREP<br />
Project website<br />
www.transdeath.org<br />
Nektarios Tavernarakis<br />
Foundation for <strong>Research</strong> and Technology<br />
Heraklion, Greece<br />
tavernarakis@imbb.forth.gr<br />
Adi Kimchi<br />
Weizmann Institute of Science<br />
Rehovot, Israel<br />
adi.kimchi@weizmann.ac.il<br />
Roberto Testi<br />
University of Rome ‘Tor Vergata’<br />
Rome, Italy<br />
malisan@med.uniroma2.it<br />
Jonathan Jones<br />
The Sainsbury Laboratory<br />
Norwich, United Kingdom<br />
dimitrios.tsitsigiannis@sainsburylaboratory.ac.uk<br />
Angelika Bonin-Debs<br />
Xantos Biomedicine AG<br />
Munich, Germany<br />
s.roehrig@xantos.de<br />
BIOLOGY 81
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