Abstract

Despite our exponentially growing knowledge about the human genome, we do not know all human genes required for some of the most basic functions of life such as somatic cell division. To start to fill this gap we developed a high throughput phenotypic screening platform combining potent gene silencing by RNA interference, time lapse microscopy and computational image processing. We carried out a genome-wide phenotypic profiiling of each of the 21`000 human protein-coding genes by two day live imaging of fluorescently labelled chromosomes. Quantitative phenotyping by computational image processing allowed us to identify hundreds of human genes involved in cell division (www.mitocheck.org ), which we are now studying in mechanistic detail in follow up studies using automated advanced fluorescence microscopy methods.

Even more than the molecular mechanisms of mitosis, many questions about the segregation of homologous chromosomes during the formation of germ cells remain open. To study this process, we have established complete kinetochore tracking by high resolution 4D imaging of the first meiotic division in mouse oocytes. Quantitative analysis of this data reveals the highly error prone nature of mammalian homologous chromosome biorientation that may provide a possible mechanistic explanation for the high incidence of chromosome aneuploidies in mammalian eggs.