A functional genomics approach to the choregraphy of genomic maintenace.

Maintenance of the genome is essential for survival of individuals and species. Failure to maintain the genome results in intrauterine death, developmental defects, premature ageing, decreased resistance to infections and cancer. DNA repair processes are functionally linked in intricate networks, and closely coupled to other cellular processes such as DNA replication, nucleotide biosynthesis, cell cycle regulation, transcription, nucleotide pool sanitation, immune responses and apoptosis. We want to study DNA repair and associated processes using a functional genomics approach, to understand these highly complex and regulated networks. Massive parallel analysis of mRNA expression after specific challenge will be used to identify co-expression of verified DNA-repair genes. Bioinformatics analysis will help generate hypothesis about genes of unknown functions. Parallel proteomic analysis using immunocapturing and mass spectrometry, as well as FRET-analysis of intracellular protein inter a interactions will help identifying proteins in repair complexes and unraveling of their functions. Our laboratory is establishing close links to recently established FUGE-platforms (bioinformatics platform, the microarray consortium and the proteomics pla tform). Our laboratory is also well connected to top national and international scientists with whom we collaborate. In general, these laboratories have complementary technological and conceptual expertise that will strongly enhance our research capabilit ies.