C2D2 research 1a - Dissecting RNA interactions in disease: from modelling gene networks to future therapies

Project: Other projectOther internal award

Project Details

Layman's description

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 combines 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. This study will form the basis for further comprehensive investigations in the role and characterisation of RNA networks in disease.

Key findings


This project initiated the construction of computational models of microRNA-driven gene networks by focusing on the miR-132/p300 interaction, as this was a well-characterised interaction with direct relevance to immune responses to pathogens. In parallel, we performed high-throughput sequencing experiments to characterise a novel RNA-binding protein that seems to regulate miR-132 abundance. We believe we made significant progress particularly with regards to the computational aspect of the project: Starting with no more than an idea we reached a point where we have a fully implemented simulation, in other words a computer program that follows the specific

biological rules required. Importantly this represents the first application of agent-based modelling to molecular networks. As expected the time available was not sufficient for full calibration of the model, which is required for publication, but it has provided a platform for the training of a PhD student and preliminary data to be included in grant applications. Indeed this collaboration set the foundation that attracted a Wellcome Trust-funded PhD student (CIDCATS programme), who is working in the project since October 2012.


This work initiated a new collaboration between the Lagos (RNA biology) and Timmis (Agent based computational modelling) groups.


Richard Greaves was the employed PDRA in the project and is currently working in a related project with Jon Timmis and Mark Coles. Sarah Hayes, a summer student in the project, was offered a PhD in Kings Collage London following this placement.


Not applicable.



Medical Research Council, Lagos, New Investigator Research Grant, miR-132 as a master regulator of the immune response, £449,869.

C2D2, Timmis, Coles, Rose, Bees, Lagos, Pollack, Consolidator Grant, Advancing Immunology through computational modelling, £91,049

NC3Rs - CRACK-IT, Phase 1, Kaye, Croft, Timmis, Alavijeh, Coles, Mottram, Walsh, A multiscale model to minimise animal usage in leishmaniasis drug development, £100,000 (Lagos to be included in Phase 2).

Not Awarded:

European Research Council, Lagos, Consolidator Grant

BBSRC, Timmis, Coles, Rose, Lagos, TDRF Grant


Exploring microRNA regulatory networks using Agent-based Modelling

Greaves R., Leonov J., Timmis J., and Lagos D.

Submitted to ICARIS International Workshop on Computational Biology

Effective start/end date1/03/1230/09/12