1.6 Biomedical research  (Page 2/5)

Among the biggest challenges from emerging infectious diseases is the relation between early detection and surveillance of the diseases, as new cases can appear anywhere. This results from the globalization of exchanges and the circulation of people and animals around the world as recently demonstrated by the avian flu epidemics. An international collaboration of research teams in Europe and Asia has been exploring some innovative in silico approaches to better tackle avian flu and more recently swine flu, taking advantage of the very large computing resources available on international grid infrastructures (Brenton et al. 2008). Existing data sources have been integrated to form a global surveillance network for molecular epidemiology, based on Service Oriented Architecture (SOA) and grid technologies. The idea is to dynamically analyze the molecular biology data, made available on public databases using computing, storage and automatic updating services offered by grid technology. Bioinformatics methods of sequence alignment can highlight mutations on a virus’s genome that could impact transmission mechanisms, pathogenicity or drug sensibility. In addition, phylogenetic analyses help to characterize evolutionary history, a key point in understanding the geographic and molecular source of this outbreak, when the virus seems to be a reassortant from avian and human forms. If another pandemic strikes, bioinformatics is expected to have an impact by adding a new weapon to researchers’ arsenal: the grid.

Grid as a discovery tool for new drugs - wisdom

Another challenge for infectious disease research is the constant mutation of the viruses. The mutation of these viruses makes them perpetual moving targets for drug and vaccine discovery. In this context, the WISDOM (World-wide In Silico Docking On Malaria) collaboration, comprised of experts on all continents, was launched in 2005 to exploit the resources of grid infrastructures for in silico drug discovery (Chien, Foster and Goddette 2002). Virtual screening is a computational technique used in drug discovery research. It involves the rapid in silico assessment of large libraries of chemical structures in order to identify those structures most likely to bind to a drug target, typically a protein receptor or enzyme. Although virtual high throughput screening (HTS) is mainly achieved through clusters of computers physically connected to one another that can screen compound sets against the target, recent advances in grid technology are allowing powerful grid-computing strategies to be applied to HTS to enlist a larger number of compute resources. Discovering hits with the potential to become usable drugs is a critical first step to ensure a sustainable global pipeline for finding innovative products to treat neglected and emerging disease (Richards 2002).

The primary goal of the WISDOM initiative was to support research on diseases that do not receive sufficient attention from the research community and pharmaceutical laboratories for the development of new drugs and vaccines, despite critical situations and the efforts of international agencies and foundations. Among neglected diseases, malaria causes more than one million deaths every year mostly in tropic and subtropic regions. Dengue fever which is also a viral disease transmitted by mosquitoes share common geographic areas with malaria with additional prevalence in urban areas of the tropics. In the meanwhile, tuberculosis has reemerged as a major threat to international public health in recent years due to its correlation with AIDS. Four years after its launch, WISDOM has been able to successfully screen a handful of biological targets involved in major societal threats like avian flu, diabetes and malaria, using very large databases of drug-like compounds. A few hundred compounds selected in silico were tested in vitro and about 20% have demonstrated significant inhibition activity against the target of interest, showing the relevance of grid technology to address drug discovery issues.