Research of this group relates to the use of FISH and immunocytochemical methods to study the molecular composition (mainly nucleic acid sequences and protein) of single cells and chromosomes. It includes the use of modern forms of fluorescence microscopy such as CSLM, two-photon microscopy and life-time imaging microscopy, as well as quantitative analysis of digital images. Recent highlights are the development of a novel molecular cytogenetic method for multicolor cytogenetic analysis (COBRA FISH), to study very complex chromosomal rearrangements, which is now successfully applied in collaboration with the Departments of Clinical Genetics and Pathology; the construction of a live cell imaging workstation allowing the study of in vivo protein-protein interactions using FRET-FLIM and the creation of a central facility for genomic and expression arraying (with the Department of Human Genetics) within the activities of the Leiden Genome Technology Center. - Future themes. The ongoing research line focusing on the study of transcription processes in live cells will be extended. It will include FISH and immunocytochemical methods to study mRNA production and processing, fluorescence life-time imaging to visualize functional association of proteins (as GFP constructs) and dynamic analysis employing 4D digital fluorescence microscopy. A two-photon microscope will be installed to follow the dynamics of molecular processes for prolonged periods of time (facility for general LUMC support). Applications of the project include the study of chromatin modelling factors (with Verrijzer), signal transduction in diabetes (with Maassen), and visualisation of expression patterns in whole Drosophila (with Noordermeer/Fradkin). A second research project develops and applies molecular cytogenetic techniques such as COBRA-FISH and comparative genomic hybridization to study balanced and imbalanced chromosomal rearrangements in pre- and postnatal diagnosis (with the Department of Clinical Genetics) and in solid tumours (with Pathology and Human Genetics). Specific topics are the role of HPV in cervical cancer, and cytogenetic characterisation of solid tumours such as colorectal cancers, sarcomas and tumours of the prostate, or head and neck region (the latter with Pathology EUR). Development of genomic and expression arraying for these topics is performed in collaboration with the Department of Human Genetics. The group will continue to develop methods for image analysis and automated microscopy and explore new technologies to study molecular composition of cells, such as fluorescence correlation spectroscopy (with Parasitology). - Research goals. The group develops and applies novel methods to unravel the molecular composition of cells and chromosomes, using FISH and immunocytochemistry methods in combination with advanced microscopical techniques such as life cell imaging, confocal laser scanning microscopy and automated digital fluorescence microscopy. Main aim is to methodologically and technologically support the cell biological research within the Department. In addition, to use these methods for other (basic) research purposes as well as for clinical application in close collaborations with the Departments of Human and Clinical Genetics, Pathology and Hematology.