Programmed cell death (PCD) is normally invoked during development and immunity, but inappropriate PCD is associated with pathologies including cancer and degenerative diseases. Conserved genes controlling apoptosis, a type of PCD dependent upon caspase proteinases, were first identified in the model organism C. elegans. This work received a 2003 Nobel Prize, and biomédical research has established related mammalian PCD pathways. However, phylogenetically conserved PCD types other than apoptosis exist i n animal and non-animal cells. This TransDeath project will focus on cellular and molecular events in these less well known cell death types. Thus, the project aims to broaden the experimental net to catch PCD regulators by comparative research on divers e organisms that each may be uniquely suited to unravel a type of conserved PCD process. The main approach will be across the eukaryotic kingdom, the main aim will be to understand these types of cell death in humans. TransDeath thereby aims to produce knowledge on genes and biochemical processes that regulate PCD in different organisms, and to apply that knowledge to develop strategies and targets for human disease therapy. Specific TransDeath objectives include: - Characterize the diversity of genes & biochemicals controlling PCD of diverse types - Functionally compare these genes & biochemicals between organisms - Derive genetic & functional models of PCD evolution - Test genes & biochemicals on PCD related to human normal function an d disease The results of this project will be of great value to the European and international scientific communities. Our efforts will strengthen European research in the strategic area of functional genomics and yield a wealth of information on gene fu nction in PCD immediately relevant to pharmaceutical R&D. Several patent applications are foreseen, to be exploited by the SME partner.
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