Biocomputational resources useful for drug discovery against compartmentalized targets.

It has been estimated that the cost of bringing a new drug onto the market is 10 years and 0.5-2 billions of dollars, making it a non-profitable project, particularly in the case of low prevalence diseases. The advances in Systems Biology have been absolutely decisive for drug discovery, as iterative rounds of predictions made from in silico models followed by selected experimental validations have resulted in a substantial saving of time and investments. Many diseases have their origins in proteins that are not located in the cytosol but in intracellular compartments (i.e. mitochondria, lysosome, peroxisome and others) or cell membranes. In these cases, biocomputational approaches present limitations to their study. In the present work, we review them and propose new initiatives to advance towards a safer, more efficient and personalized pharmacology. This focus could be especially useful for drug discovery and the reposition of known drugs in rare and emergent diseases associated with compartmentalized proteins.

The Virtual Liver Network: systems understanding from bench to bedside.

Adriano Henney speaks to Hannah Coaker, Commissioning Editor. After achieving a PhD in medicine and spending many years in academic research in the field of cardiovascular disease, Adriano Henney was recruited by Zeneca Pharmaceuticals from a British Heart Foundation Senior Fellowship, where he led the exploration of new therapeutic approaches in atherosclerosis, specifically focusing on his research interests in vascular biology. Following the merger with Astra to form AstraZeneca, Henney became responsible for exploring strategic improvements to the company's approaches to pharmaceutical target identification and the reduction of attrition in early development, directing projects across research sites and across functional project teams in the USA, Sweden and the UK. This resulted in the creation of a new multidisciplinary department that focused on pathway mapping, modeling and simulation and supporting projects across research and development, which evolved into the establishment of the practice of systems biology within the company. Here, projects prototyped the application of mechanistic disease-modeling approaches in order to support the discovery of innovative new medicines, such as Iressa®. Since leaving AstraZeneca, Henney has continued his interest in systems biology, synthetic biology and systems medicine through his company, Obsidian Biomedical Consulting Ltd. He now directs a major €50 million German national flagship program ­ the Virtual Liver Network ­ which is currently the largest systems biology program in Europe.

From the first drop to the first truckload: commercialization of microbial processes for renewable chemicals.

Fermentation of carbohydrate substrates by microorganisms represents an attractive route for the manufacture of industrial chemicals from renewable resources. The technology to manipulate metabolism of bacteria and yeast, including the introduction of heterologous chemical pathways, has accelerated research in this field. However, the public literature contains very few examples of strains achieving the production metrics required for commercialization. This article presents the challenges in reaching commercial titer, yield, and productivity targets, along with other necessary strain and process characteristics. It then reviews various methods in systems biology, synthetic biology, enzyme engineering, and fermentation engineering which can be applied to strain improvement, and presents a strategy for using these tools to overcome the major hurdles on the path to commercialization.

New and improved proteomics technologies for understanding complex biological systems: addressing a grand challenge in the life sciences.

This White Paper sets out a Life Sciences Grand Challenge for Proteomics Technologies to enhance our understanding of complex biological systems, link genomes with phenotypes, and bring broad benefits to the biosciences and the US economy. The paper is based on a workshop hosted by the National Institute of Standards and Technology (NIST) in Gaithersburg, MD, 14-15 February 2011, with participants from many federal R&D agencies and research communities, under the aegis of the US National Science and Technology Council (NSTC). Opportunities are identified for a coordinated R&D effort to achieve major technology-based goals and address societal challenges in health, agriculture, nutrition, energy, environment, national security, and economic development.

Systems biology: evolving into the mainstream.

Systems approaches to biology are steadily widening their reach, but the road to integration and acceptance has been fraught with skepticism and technical hurdles. Interdisciplinary research teams at systems biology centers around the globe are working to win over the critics.