

Hepatocellular carcinoma (HCC), a type of liver cancer, is one of the most common malignancies worldwide, and largely remains an incurable disease. Gene expression profiling studies have identified several molecular pathways that are deregulated or mutated in HCC, but the fundamental mechanistic determinants of HCC remain largely unknown.
MODHEP (MODelling HEPatocellular carcinoma) is a five and a half year research project that aims to elucidate the fundamental nature of one of the world’s deadliest cancers. The concept at the heart of the project is that the pathologic behaviour of cancer cells is controlled by an abnormally reprogrammed genome, and so understanding cancer requires that the molecular basis for genome reprogramming be unravelled and described within an integrated model.
To this aim, MODHEP are producing an integrated analysis of the nuclear changes occurring in two complementary multi-stage models of liver cancer. A coordinated, multi-faceted and quantitative series of datasets will be generated by the different labs in the consortium, forming a complete description of the genetic, epigenetic and nuclear organisational aberrations occurring both at pre-tumoural and tumoural stages of the disease. A combination of innovative systems biology-based approaches will then bring together the analysis of functional pathways with computational models of genomic, epigenomic and three-dimensional nuclear organisation.
The film, created by Insight, explains the nature of liver cancer and also follows the project through a five-day symposium that took place in Yokohama, Japan, where the consortium gathered to discuss the progress of the project and plan for the future. The film also explains how the project has pioneered the development of new technologies to aid cancer research, while the global nature of the partnership emphasises the importance of international collaboration in the fight against all cancers.
Project coordinator Bruno Amati gives an overview of the project and explains how partners with different areas of specialist knowledge are coming together to provide a global picture of genome organisation. There are also further interviews with Wouter de Laat of the Hubrecht Institute, Yu Wei of the Institut Pasteur, Valerio Bianchi of Instituto Italiano di Technologica, Piero Carninci of RIKEN, Guiseppe Testa of the European Institute of Oncology and Kosuke Hashimoto of RIKEN. The partners explain each of their specialist elements and how they fit into the project, ranging from 3D modelling of the genome inside the cell nucleus to the use of CAGE technology.
MODHEP is now in its final year and has amassed a huge amount of data that is being used to provide a 360-degree, multi-layered analysis of genome organisation and function, with a view to identifying key molecules that will one day be targets of drugs that can eradicate HCC. MODHEP is targeting specific aspects of one type of cancer, but the knowledge and techniques pioneered within the project can provide a model that can be used to enhance understanding of many other diseases.
For more information and to view the film please visit http://www.projectsmagazine.eu.com/video/the_modhep_project_understanding_liver_cancer
For more information about MODHEP please visit www.modhep.eu
There are also two further cuts of the film. The first combines all of the animation created for the film by Insight Publishers, giving a clear overview of the project’s objectives. The second contains the interviews from the film, providing a more detailed analysis of each of the different partner elements that make up MODHEP.
These can also be viewed on the Projects website at www.projectsmagazine.eu.com