In eukaryotes, many steps of gene expression, such as transcription and RNA processing, take place in the structurally complex environment of the nucleus and often involve remodelling of chromatin into active and inactive states. Messenger RNAs, once exported from the nucleus, undergo additional regulatory steps.
Their translation results in the production of proteins, whose functions define the characteristics of different cell types, or cellular phenotypes. Not all RNAs are translated, however. In recent years, multiple types of non-coding RNAs have been discovered that display diverse functionality. Genetic variation in non-coding and protein-coding genes alike, as well as the regulatory elements that govern their expression, can adversely affect the function of these genes, leading to diseases such as cancer. Groups within the Unit are investigating various aspects of genome biology in order to understand these processes leading from genotype to phenotype.
A notable strength of the Unit is its ability to address questions at different scales, ranging from detailed mechanistic studies (using biochemistry, genetics, microfluidics and chemistry) to genome-wide studies (using functional genomic, proteomic and computational approaches), often by developing new enabling technologies. For example, the development and integration of chemistry and microfluidic devices with the recent advances in next-generation sequencing will facilitate major advances in these areas in the coming years. Global, dynamic and quantitative measurements of biological molecules at all levels (DNA, RNA, proteins, cells, organisms, etc) as well as the integration of hypothesis and discovery-driven research characterise the Unit. The synergy between computational and wet-lab groups provides a very interactive and collaborative environment to yield unprecedented insights into how genetic information is ‘read’ and mediates phenotype through molecular networks.