The completion of the Human Genome Project and the emergence of high-throughput technologies at the dawn of the new millennium, are rapidly changing the way we approach biological problems. Reductionism, which has dominated biological research for over a century, has provided a wealth of knowledge about individual cellular components and their functions. Despite its enormous success, it is increasingly clear that a discrete biological function can only rarely be attributed to an individual molecule. Instead, most biological characteristics arise from complex interactions between the cell's numerous constituents, as well as from the interplay of different cell types, as these are defined in vivo by the tissue microenvironment. Therefore, key challenges for biology in the twenty-first century are the exploration of the structure and the dynamics of this complex inter- and intra- cellular web of interactions that contribute to the structure and function of a living cell. In this context and towards that end, we are implementing and integrating a variety of functional genomics (reverse genetics, expression profiling and bioinformatics) methods and tools in holistic, multidisciplinary explorations of pathogenetic mechanisms.