Climbing to the next level: the German Virtual Liver Network

In April 2010, an ambitious new project was launched in Germany: The German Virtual Liver Network. Funded by the Federal Ministry of Education and Research (BMBF), this major interdisciplinary research initiative is the only one of its kind in the world that focuses effort on a single organ across multiple scales of complexity. With an allocated budget over five years of approximately 43 million euros, it is also the only research network worldwide to be financed by a single national organization in systems biology.

The Network’s goal is to create a computer model of the liver as a complete organ with all of its diverse and essential functions. Thus it should be possible to better understand the processes in the liver and to develop tailor-made medications.

A biochemical factory in the body
The liver is a unique organ: as the central metabolic organ of vertebrates, it synthesizes, converts and breaks down more than 10,000 substances daily, helping the body to digest food and detoxify itself. It aids digestion, controls iron uptake and synthesizes vital proteins such as coagulation factors. Furthermore, hepatic metabolism is a major factor that needs to be considered in drug development, as it is central to toxicity and drug efficacy. The exploration of the liver and its functions by the Network is therefore of the greatest relevance to medicine and the pharmaceutical industry.
Looking to the future with systems biology
In order to get an overall picture both of the liver as a whole and of the diverse and dynamic processes in the organ, the Network’s researchers are looking to systems biology for help. This branch of science, which deals with the exploration of biological processes at the systems level, seeks to create a holistic picture of dynamic life processes at all levels – from the genome to the proteome and up to the complete cell or even an entire organism. In order to achieve this goal, systems biology links quantitative methods from the field of molecular and cellular biology with techniques and tools from the areas of mathematics, computer sciences and systems sciences. “Systems biology can accelerate the transfer from academic research to use on patients and can cut costs in the development of medications. That’s why it is a key technology and a driving force of innovation for individualized medicine of the future,” emphasizes Federal Minister for Education and Research Annette Schavan in a BMBF's press release in July 2010.
From the cell to the whole organ
In recent years, the HepatoSys network dealt intensively with the systems biology of the liver cell. Building on these results, the project’s successor, the German Virtual Liver Network, now aims to understand the processes in cell aggregates up to the entire organ. For this ambitious project spanning the entire nation, 70 research groups from 41 institutions in science and industry have joined forces. Together these scientists aim to develop integrated computer models capable of generating experimentally testable predictions that are relevant to the physiology of the liver, as well as the function of the organism, and how this is disturbed in disease. This will contribute to an improved understanding of the liver as the body’s most important metabolic organ and how its function is affected in disease. By using validated simulations, these models will greatly benefit efforts to find new therapies, to predict how active substances distribute in the organ, where they attack, and how quickly they are broken down. Thus, medications can be developed in a more targeted, efficient and cost-effective manner and tailored to deliver the optimum dosage to the right patient at the right time.
A world leader
The German Virtual Liver Network is the first project worldwide to aim at building a truly multi-scale computer model of a complete organ– from the biomolecular and biochemical processes up to the anatomy of the whole organ – and including them in the simulation. “The challenge is immense, but we are looking forward to accepting it – not only to promote an understanding of the liver, but also to provide a strong impetus to the entire area of systems biological research. Our goal is to give evidence of a genuine impact on healthcare” says Adriano Henney, program director of the German Virtual Liver Network.