Infectious diseases: Reacting faster and more effectively
Berlin – Germany has launched Europe’s first civil high-throughput screening facility for high-risk infectious agents within the framework of ERA-NET PathoGenoMics. The novel bio-safety level 3 (BSL3) unit at the Max Planck Institute for Infection Biology in Berlin was inaugurated in mid-September by representatives from the German Research Ministry and the Max Planck Society. The next step will be to carry out functional RNAi screens in flu-infected host cells to find new targets and drug leads.
Circumventing microbial resistance
Identification of drug candidates against multi-resistant bacterial pathogens will also be a priority for the team of Max Planck researchers under Professor Thomas Meyer. Infectious diseases are still the world’s second most frequent cause of death in spite of improvements in hygiene, vaccination campaigns and further development of antibiotics. Researchers currently use two scientific strategies to nail down promising drug candidates. The hypothesis-driven approach focusses on the investigation of distinct virulence processes, while the global analysis approach employs high-throughput technologies and bioinformatics to identify the most critical factors in pathogenesis. The latter has been gradually gaining in importance. Within the framework of ERA-NET PathoGenoMics, the Max Planck Society and German Ministry of Education and Research (BMBF) have now kicked-off Europe’s first high-throughput screening facility for highrisk pathogenic agents. The BSL3 (biosafety level) unit comprises a screening robot, as well as the necessary periphery infrastructure such as molecular biological BSL3 labs and state-of-the-art high-throughput microscopy and read-out devices. Its prime purpose will be to conduct screens with bacterial pathogens causing plague, typhus, tuberculosis and other deadly diseases.
First project: RNAi screen against pandemic influenza
The recent flu pandemic has also led to an expansion of that brief. The institute is now preparing to screen for drug candidates against pandemic influenza and is searching support from the EU FP7 HEALTH programme. Targeting host-cell compounds The researchers will be testing a new strategy for overcoming the ability of flu viruses to change their phenotype, thus escaping current therapeutic regimes. Influenza A viruses exhibit intrinsic mechanisms for generating altered viruses: their genome consists of 8 genome segments that can be quickly re-assorted upon viral coinfections, a process called antigenic shift. Such viral recombinants exhibit severely altered surface structures, allowing them to slip under the immune system’s radar. Moreover, virus replication facilitates the generation of point mutations, giving rise to a steady ‘antigenic drift’ and viral escape mutants. Such viral escape mutants clearly hamper efficacy of available flu treatments, as existing anti-virals are directed against bona fide viral targets, which risks generating therapy resistance. The new project is aimed at benefiting from the fact that viral infection and replication intimately depend on factors provided by the host cell.
Focus on targets essential for the virus
The MPI team will target host cell factors that are dispensable for the host but essential for virus replication. Using high-throughput RNA interference technology, they will scan the entire human genome for critical determinants of infection. Identification of these determinants will lead to promising therapeutic solutions for the most important human virus infections. The approach can also be applied to other viral infections with pandemic potential, according to Meyer. “During the past few decades, new viral diseases such as AIDS, SARS and Nipah Virus Encephalitis have emerged. On top of that, known viral agents are in the process of changing their behavior and location because of i.e. climatic variations or international traffic.” Meyer is convinced that the new project represents a necessary and timely search for suitable targets and effective drugs against devastating infections that have high mortality rates.