Our body is composed of billions of cells, each of them achieving a specialized task. For example, our flat skin cells ensure protection from external physical and chemical aggressions whereas our rod-like photoreceptor cells in the eye allow light to be sensed in our environment. Despite this variability in structure and function, almost all cells in our body have exactly the same genome, the DNA sequence where our genetic information is stored. As an analogy, one could think of the genome as the hard disk of a computer, where every program for each cell type is stored but in each cell only one of these programs is executed.
The genome is physically separated from the rest of the cell within a specialized organelle, the nucleus. A high level of compaction is achieved: our genome is 2 meters long but stored in a ball of a diameter of 5 micrometers (the nucleus). This would correspond to a very thin wire the length of the distance from Zürich to Geneva stored within a basketball. The compaction of this wire is, however, neither homogenous nor constant: some regions of the genome are very densely wrapped while others are looser. This compaction level along the wire, as well as the spatial distribution of the genome (where a given segment of the wire is located inside the nuclear ball) is unique to each cell type and setup when cells acquire a specialized function. Moreover, problems in structural components of the nucleus have been shown to be causal in a number of diseases. These point to the importance of the organization of the genome in space inside the nucleus. What we aim to discover is.
The link between the execution of a given program and the subnuclear 3D localization of the individual genes – lines of codes – that achieve that program; the rules that govern gene localization.
What holds the different parts of the wire at defined places inside the nucleus.
The effect of changing the localization of individual genes and/or parts of the wire on the program and function of the cell.
The organism which is used for these studies is the roundworm C. elegans. This simple animal is found in our gardens on rotting fruits, its fast life cycle (3 days) makes it an ideal laboratory model. It is one of the best-known organisms in which individual different cells achieve specialized tasks (as the skin or photoreceptor cells). Since much of the machinery involved in organizing the genome in 3 dimensions is evolutionarily conserved, the knowledge gained in the roundworm will improve our understanding of the gene expression program also in more complex animals like humans where such studies are not yet possible. The characterization of what is responsible for nuclear organization will also shed light on the mechanisms that underlie induced changes in these expression programs. This knowledge will improve our comprehension of cancer appearance, where cells change their function and begin to divide anarchically. It will also help us understand how cells can revert to non-specialized states, an emerging field full of therapeutic promises..
