Dissecting RNA interactions in disease: from modelling gene networks to future therapies

Overview

Significant changes in the abundance of individual proteins within a cell can result in faulty cellular functions. An accumulation of such functions leads to disease. This project set out to combine cutting edge molecular biology studies with computational modelling to understand the processes that cause these changes in a group of key proteins known as RNA-binding proteins or RBPs. The study was intended to form the basis for further comprehensive investigations in the role and characterisation of RNA networks in disease.

Computational models of microRNA-driven gene networks were constructed which focused on the miR-132/p300 interaction as this was a well-characterised interaction with direct relevance to immune responses to pathogens. In parallel, high-throughput sequencing experiments were performed to characterise a novel RNA-binding protein that seems to regulate miR-132 abundance. This computer modelling programme represents the first application of agent-based modelling to molecular networks. The interaction between the two research groups has generated an exciting cross-disciplinary framework, which has attracted a Wellcome Trust-funded PhD student from the CIDCATS (Combating Infectious Disease: Computational Approaches in Translational Science) programme. This student's work will follow up directly on the experimental findings and computational approaches built during this three-month project and work towards fully calibrating the model.

Outputs

Grants

• Dimitris Lagos, MRC New Investigator, The role of miR-132 in the immune response to pathogens, £449,869