Susan M. Gasser
Functional organization of the nucleusWe are interested in how nuclear organization impinges on mechanisms of repair and replication fork stability and on epigenetic inheritance of cell fate decisions. We combine genome-wide mapping, synthetic lethal screens, quantitative live fluorescence imaging, biochemical reconstitution and standard yeast molecular genetics to address these questions at the molecular and cellular levels. In questions of stem cell determination and epigenetic inheritance, we work with C. elegans to study the effects of nuclear organization on gene expression during well-characterized cell differentiation events.
Having developed the means to study the position of genes in living, differentiating cells of C. elegans, we showed that tissue-specific genes shift from an inactive position at the nuclear lamin to a lumenal position during differentiation. In contrast to differentiation-specific genes, heat-shock promoters shift to the nuclear periphery when active. Introducing into C. elegans a mutant lamin that causes muscular dystrophy in humans, we demonstrated that a muscle-specific promoter does not shift inwards in muscle. This impairs its tissue-specific activation and muscle function.
Susan Gasser leads a Swiss SystemX RTD project called Cell Plasticity in Health and Disease that involves 8 laboratories along with the computational biology platform of the FMI. The goal of Cell Plasticity is to develop a systems-level understanding of the gene regulatory networks responsible for cellular differentiation in mice. We focus in particular on modeling mechanisms through which the sequence-specific binding of transcription factors interacts with the dynamics of the epigenetic code along the genome, i.e. the local status of chromatin as determined by histone and DNA modification. To derive general regulatory principles, we propose to study a panel of mouse cellular differentiation systems, including four normal differentiation processes and two cancer-related transformation events. All these systems have well-defined differentiation time courses with defined cellular states that allow collection of homogeneous populations of cells.
FMI report pages for Susan M. Gasser
Susan M. Gasser