Interaction networks: the new path to drug discovery

Apr 17 2008

Although the pharmaceutical industry has dedicated enormous research efforts over the last 50 years to identify new targets and develop new active ingredients, these efforts have met with limited success.

One of the main reasons for the failure of many molecules is because the studies have focused, almost exclusively, on the relation between the target protein and the drug. However, molecules rarely work alone but rather form part of a series of connected networks, signaling pathways and interactions. Researchers now believe that drug development calls for a broader view, which contemplates the global properties of the complex systems responsible for the regulation of most biological processes. This change in paradigm, included in the so-called “Systems Biology” approach, is the focus of the next Barcelona BioMed Conference, “Targeting and Tinkering with Interaction Networks”, organised by the Institute for Research in Biomedicine (IRB Barcelona) and the BBVA Foundation. Held from 14-16 April at the Institut d’Estudis Catalans, in Barcelona, this conference will bring together 23 leading authorities in this field from around the globe.

The genome projects carried out over the last 10 years worldwide have provided almost complete lists of the molecular components of diverse organisms, including humans. “While this information is vital, it’s really only the beginning,” says Patrick Aloy, ICREA researcher and group leader in Systems Biology at IRB Barcelona and co-organiser of the Barcelona BioMed Conference. “We have the parts lists, but now we need to figure out how all these elements work together in order to begin to understand how physiological processes occur and what happens when something goes wrong, for example, in disease.”

Why, when you modify a protein that inactivates a certain step in a disease process, are a series of other vital processes in the organism affected related to the protein you altered? Or why, when you try to block the effect of a single molecule in a signaling pathway, does a backup system kick in and ensure that the signal still arrives? “Because several processes and interactions are at work. We need to understand this as a whole – not just as individual components,” explains co-organizer Rob Russell, group leader at the European Molecular Biology Laboratory in Heidelberg, Germany. “Once we have a better idea of the complex systems involved, we can design drugs that don’t just target single molecules, but ones that aim to change the behaviour of an entire network of interactions.”

Unraveling the mysteries of systems biology will require the concerted effort of researchers from a wide range of disciplines. Huge amounts of data need to be integrated, and complex systems modeled and then tested in physiological conditions. This diversity is reflected in the list of speakers for this conference, which includes biocomputational scientists, molecular and cell biologists, pharmacologists, from both academia and industry.

From basic to pharmacological researchers

Patrick Aloy (IRB Barcelona, Catalonia, Spain). Aloy’s group designs new bioinformatics methods in order to obtain complete maps of cell molecular machinery. The information attained can pinpoint weak points that may be useful to design new drugs.

Marc Vidal (Center for Cancer Systems Biology, Dana-Faber Cancer Institution, Boston, USA). Vidal addresses questions devoted to the protein-protein interaction networks organised at the scale of the whole cell, in order to reveal how these networks are modified in human diseases such as cancer.

Ron Weiss (Princeton University, USA). Ron Weiss is a computational scientist. His group follows a computational/experimental approach to engineer complex behaviour in living systems, ranging from bacteria to stem cells. In their research, they apply design principles taken from electrical engineering and other well established fields, to stimulate, for example, the differentiation of stem cells into different cell types.

Víctor de Lorenzo (Centro Nacional de Biotecnología, Madrid, Spain). De Lorenzo’s group implants sensor proteins and sensor circuits into bacteria destined for environmental release. In his lab, they have design environmentally safe strains for the detection of explosive residues in soil.

Jay Keasling (University of California, Berkeley, USA) Keasling uses synthetic biology to develop inexpensive, effective, antimalarial drugs. In the lab, which is funded by the Bill and Melinda Gates Foundation, they are trying to take genes from the wormwood tree and yeast and get them to work together in E. coli bacteria to produce artemisinin, a malaria drug currently extracted from the wormwood tree in a costly process.

David de Graaf (Pfizer, Cambridge, USA). De Graaf, Chief Scientific Officer at Pfizer, identifies targets and signaling pathways involved in the processes of disease. He will present preliminary results of a study on rheumatoid arthritis