Ben Luisi (Department of Biochemistry, University of Cambridge):
Bacterial non-coding RNA and regulatory networks of gene expression
Bacteria, such as Escherichia coli and Salmonella, encode 100 or more small RNAs that do not encode protein, but instead play roles in the regulation of gene expression. These 'riboregulators' can amplify or attenuate the expression of genetic information, depending on context. They can function redundantly, so that several act on a common target, or act on multiple targets to affect multi-output, feed-forward or feed-back processes. In this way, the riboregulators confer capacity to respond in complex ways to environmental changes and maintenance of metabolic homeostasis. Key aspects of riboregulator activity is its fast action and apparent specificity, and these properties may be attributed in part to recognition of targets through base-pairing, although the rules for understanding the speed and fidelity are not completely understood. The riboregulators compete for a limiting factor that facilitates their activities, and this competition likely results in a dynamic interplay of networks. One of the regulatory mechanisms of the riboregulators involves silencing of targeted transcripts, and examples will be described of how this might be achieved with accuracy and speed.
Shamith Samarajiwa (Computational Biology Group, Department of Oncology, Cambridge University and Cancer Research UK Cambridge Research Institute):
Exploring human anti-proliferative and cell survival responses using pathways, networks and integrative genomic approaches.
Cell proliferation is tightly regulated in mammalian cells, loss of control and aberrant proliferation often results in tumour formation. A number of different mechanisms mediate anti-proliferative and cell survival effects. We explore some of these mechanisms using integrative genomics approaches coupled with pathway and network modelling. Cellular senescence, (a mechanism of permanent cell cycle arrest) and apoptosis can assist in escaping tumorigenesis. Some of the key transcription factors, pathways and regulatory networks mediating these effects were revealed by integrating gene expression and next generation sequencing technologies. A number of host defence molecules mediate anti-proliferative effects in many cell types. We explore the anti-proliferative effects mediated by Interferons, a class of host defence molecules with potent anti-viral, anti-tumour and immuno-modulatory properties. Breast cancer cell lines treated with Interferons together with genomic and transcriptomic datasets generated from breast tumours were used to explore the anti-proliferative pathways and networks involved in interferon mediated anti-tumour effects. Understanding connectedness, information flow and regulatory interactions at a systems level can assist in inferring the genetic basis of some of these phenotypes.