The Wellcome Trust Centre for Cell Biology

The seventeen research groups that currently comprise the WTCCB occupy the Michael Swann Building on the King’s Buildings Campus of the University of Edinburgh.

The human body is, astonishingly, made up of some 50 trillion cells, every one of which contains an entire copy of the human genome and all the machinery needed to duplicate itself. The basic premise of the discipline of cell biology is that living cells are more than extremely small test tubes. The many biochemical reactions taking place in all cells form pathways that are highly organised; physically, in space and in time. The goal of the Wellcome Trust Centre for Cell Biology (WTCCB) is to gain new insights into how cells function at levels from molecular interactions to complex systems.

The determination of the genetic code in the 1950s was a key advance in biology and, arguably, in human history. The realisation that the linear sequence of DNA was the key data storage system in the cell, from which most other activities could be programmed was an amazing insight. This was ultimately followed by sequencing of the human genome, together with genomes from many microorganisms, plants and animals. However, while very valuable, these sequence data certainly did not provide a complete understanding of cell function.

The recent explosion of genomic data has revealed, in unprecedented detail, the origin of human genetic variation and disease susceptibility. Genomic discoveries are pinpointing the precise origin of disease states, but are also forcing us to confront our profound ignorance of the relationship between most gene products and cellular physiology. Why, for example, do mutations in genes expressed in all cell types often affect just a single tissue or organ? The problem is compounded by growing evidence that disease predispositions are very frequently determined by mutations outside protein coding regions, which account for only a tiny percentage of the human genome. There is evidence that these mutations often affect key steps in gene expression - transcription regulation, RNA processing, RNA stability or translation - but mechanistic details are sparse. These emerging genetic insights highlight our lack of understanding of the key molecular and cellular mechanisms whose malfunction underlies many disorders.

To address these crucial issues, the WTCCB has assembled a critical mass of outstanding researchers and developed state-of-the-art facilities, giving us an exceptional ability to understand key mechanisms through multiple approaches. Researchers in the WTCCB are attempting to understand and integrate events in pathways that have previously been studied in isolation. Although our work is investigator led – with individual group leaders free to follow their scientific intuition and curiosity – there are focal themes. One major theme of research in the Centre deals with the regulation of the flow of genetic information from the DNA in the genome into RNA and hence into cellular systems. The synthesis, maturation and degradation of RNA lies at the heart of the information processing system of all organisms. Recent analyses in yeast and human cells have cast light on the intimate interconnections between all stages of the gene-expression pathway. Another underlying research theme is the study of how cells establish their polarity, grow and accurately segregate their chromosomes during division. Our recent work on chromosome structure and segregation has revealed mechanisms that allow mitotic chromosomes to adopt their characteristic structure and molecular details of the machinery driving chromosome segregation.

Work in the Centre is increasingly focussing on the broad field of cellular epigenetic mechanism, aiming to understand the interrelationship between underlying genetic alterations and their manifestation as cellular phenotypes. The term epigenetics was coined by Conrad Waddington, the former Professor of Genetics in Edinburgh, as “the branch of biology which studies the causal interactions between genes and their products which bring the phenotype into being”. This definition embraces all systems controlling gene expression in eukaryotes and encompasses the themes of our research. By bringing together the major themes of nuclear organisation, genome packaging and transmission, chromatin states and RNA biology, we aim to chart key interconnections between these processes and identify their mechanisms and regulation.