Vertical Integration Across Biological Scales

One of the ultimate challenges in biomedical research is to fit together the different levels at which complex biological systems function, from genes, through to cells, and up to the whole organ and organism. The growing area of in silico biology, which applies computing power to a wide range of biological problems such as gene networks and cell-cell interaction networks, is beginning to exploit the staggering quantity of data being generated at each level from genomic approaches.

Future Deliverable
The construction of a prototype epithelial-based in silico model organ which can be used to develop models of organs

The Beacon Project, being undertaken by Professor Anne Warner and colleagues at University College London promises to move this area forward very significantly in the UK. All the contributors to the project are members of the UCL Centre for Mathematics and Physics in the Life Sciences and Experimental Biology (CoMPLEX). The long-term aim of this exceptional team is to build an in silico model of the liver.

The development of a new computing framework to allow the execution of ‘modular’ biological models. This allows scientists to work on separate sections of a large and complex system for them to be combined later.

Sophisticated mathematical techniques for rigorously analysing the effect of simplifying a biological model.

The potential benefits of such in silico models are huge and may be applied far wider than the pharmaceutical industries. These include computational chemistry and environmental modeling in which multi-level model integration is also important.

Pharmaceutical Applications

  • speeding up the early stages of disease analysis and drug discovery
  • reducing the need for animal testing
  • novel approaches to understanding how diseases develop by shedding light on how a mutational defect in a protein impacts at the whole organ level

It is anticipated that a range of software packages and biological models will be the long term output from this highly ambitious project

Computational modeling approaches which integrate information across biological scales are still a far-off goal. The UCL team will tackle multiple biological hierarchies and plans to integrate models which range from gene regulatory networks to the interaction of cells within an organ. Getting the different models to ‘talk’ to each other presents one of the most significant challenges of the project.

Industrial Interaction
There is already considerable interest from the pharmaceutical industry and the group is actively seeking input from other areas

Experimental work is an integral part of the work of the biologists on the project, to fill in gaps highlighted by on-going reconciliation of the models with the experimental data that underpin them.

Significant Achievement
The construction of the first models describing the release of glucose in hepatocytes in response to stimulation of cell surface receptors by adrenaline.

For further details on this project please see the project website or contact the team leader Professor Anne Warner Department of Anatomy & Developmental Biology, University College London, Tel: 020 7679 7279

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