Until very recently, studies of living systems have been forced to take a very focused approach to understanding the world around us. Classical genetics has typically been limited to the dissection and understanding of individual genes or pathways. This approach can only teach us so much about cellular systems, it is self-evident that many genes are active across diverse systems and are likely to fulfil a variety of functional roles. Understanding these genes fully necessitates a broader view of biology and a more holistic approach to genetics. It is this that has led to the development of systematic, high-throughput approaches coupled to computational analysis of large volumes of data.
In the 27 October 2014 issue of Developmental Cell, the Carazo Salas Lab report the completion of an extensive screening experiment that has generated three-dimensional image-based data for over 3000 different genetic mutants and has analysed them for defects in three fundamental, highly-conserved cellular processes: cell shape, the microtubule cytoskeleton and progression through the cell cycle.
The shape of different cells is often tightly linked to their function in multicellular organisms and can be highly diverse. In other areas of life it has also been shown to be a major selection factor in evolution. The microtubule cytoskeleton forms a network of fibres throughout the cells of all complex life, acting as a transport network within cells and influencing factors as diverse as shape, motility, division and signalling. All cells arise by division of other cells as a result of the cell cycle, which governs the correct duplication and separation of genetic material between new cells, it is perhaps the most essential and tightly regulated of all biological systems.
As a result of this analysis, 262 genes have been linked to these three cell functions, with many of them being shown to function across processes. Over 10% of these genes had no previously known function, whilst many of the others have been allocated new roles in one or several of these three processes. What is more, the complete results of this screen can be viewed through a new online resource that provides direct access to many of the images used in this work in addition to all of the raw computational results used in the selection of genes and their allocation to different roles.
This paper reports several key findings. There is a major, but not total, overlap between genes regulating cell shape and microtubule cytoskeleton. Genes implicated in cell cycle regulation can be independent of cell size control. There is a complex interplay between different features of cell shape and cytoskeleton, as highlighted by Bayesian analysis. Most exciting, however, is the proposal of a mechanism, conserved in humans, that suggests regulation of interphase microtubules by DNA repair factors, which has the potential to connect with previous clinical work exploring the link between microtubules and cancer progression.
More details can be found on the University website
The paper, 'A Genomic Multiprocess Survey of Machineries that Control and Link Cell Shape, Microtubule Organization, and Cell-Cycle Progression', has been published in 'Developmental Cell' vol 31 (2) pages 227–239, and is available on Science Direct at : http://www.sciencedirect.com/science/article/pii/S1534580714005917