Participant 1. Nektarios Tavernarakis (NT), PhD, Coordinator
Institute of Molecular Biology and Biotechnology, Greece
General: The focus of our research is to identify and characterize the molecular events that transpire during degenerative, necrotic cell death, using the simple nematode Caenorhabditis elegans as our primary experimental model organism. NT is the recipient of an International Human Frontier in Science Program Organization (HFSPO) long-term award and is an European Molecular Biology Organisation (EMBO) Young Investigator.
Role in the project: We are interested in the development of a Minos-based system for mutagenesis and transgenesis in C. elegans. One outstanding problem in C. elegans research is the lack of tools and methodologies for straightforward insertion of single copy exogenous DNA in the nematode genome. Minos is a transposable element with the capacity to carry large inserts that is active in virtually every organism tested. Acquisition of a similar functionality in C. elegans would allow implementation of strategies, currently routine in other model organisms such as enhancer–trapping and others, thus greatly boosting the value of the nematode in biomedical research. Within the frame of the proposed programme our tasks will include:
Expertise/Resources: Our group has extensive expertise in genetic and molecular approaches to basic biological processes, using C. elegans. Through a number of studies, we have demonstrated the advantages of the nematode model in elucidating the molecular mechanisms of neuronal function and dysfunction (Tavernarakis et al., Neuron Vol. 18, pp. 107-19). Furthermore, we have developed innovative tools that allow efficient and rapid genetic manipulations in this organism (Harbinder et al., PNAS Vol. 94; pp. 13128-33, Tavernarakis et al., Nature Genetics Vol. 24 pp. 180-83). We initiated and are currently pursuing the dissection of the mechanisms underlying necrosis and neurodegeneration at the molecular level (Xu et al., Neuron, Vol. 31 pp. 957-71). These studies have already yielded significant new information on the biochemical events that transpire during neurodegeneration (Syntichaki et al., Nature, Vol. 419, pp. 939-944) and have up to now culminated in the elucidation of key aspects of inappropriate cell death (Syntichaki and Tavernarakis, EMBO Reports, Vol. 3 pp. 604-9). Currently our efforts focus on identifying genetic suppressors of neurodegeneration in C. elegans and examining their role in the process of cellular destruction, as well as their effects in animal models of human neurodegenerative disorders. We have a strong background in nematode genetics and transformation, in molecular biology and biochemistry techniques, in microscopy and in computational biology.
Recent Publications:
1. Syntichaki P. and Tavernarakis N. (2003). The biochemistry of neuronal necrosis: Rogue biology? Nature Reviews Neuroscience, 4: 672-684.
2. Syntichaki P., Xu K., Driscoll M. and Tavernarakis N. (2002) Specific aspartyl and calpain proteases are required for neurodegeneration in C. elegans. Nature, 419: 939-944.
3. Syntichaki pp. and Tavernarakis N. (2002) Death by necrosis: Uncontrollable catastrophe or is there order behind the chaos? EMBO Reports, 3: 604-609.
4. Xu K., Tavernarakis N. and Driscoll M. (2001) Necrotic cell death in C. elegans requires the function of calreticulin and regulators of Ca2+ release from the endoplasmic reticulum. Neuron, 31: 957-971.
5. Tavernarakis N., Everett J., Kyrpides N. and Driscoll M. (2001) Features of the intracellular amino-termini of DEG/ENaC ion Channels. Current Biology 11: R205-R208.
6. Tavernarakis N., Wang S. L., Dorovkov M., Ryazanov A. and Driscoll M. (2000) Heritable and controllable interference by dsRNA. Nature Genetics 24: 180-183.