Rahul Roy, Associate Professor in the Department of Chemical Engineering at the Indian Institute of Science (IISc), is leading an international team that has received a research grant of one million dollars over three years from the International Human Frontier Science Program Organization, to study how viruses overcome the cell’s barrier (the cell membrane) and initiate infection.
Many pathogenic viruses carry a lipid membrane coat (derived from the cells they have previously killed) to help them mimic the cell’s exterior. When the viruses are ready to infect, they fuse this coat with the cell’s membrane to start the infection inside the new cell. This membrane fusion process is not spontaneous and viruses carry dedicated proteins for this job. Sitting on the virus’ outer surface, these ‘envelope’ proteins perform a complex set of ‘molecular acrobatics’ to facilitate this fusion. Capturing these steps at the molecular level has been hard till now.
The Human Frontier Science Program (HFSP) grant gives Roy and his team, including Stefan Howorka (University College London, UK) and Aleksei Aksimentiev (University of Illinois, Urbana-Champaign, USA), the opportunity to develop techniques that elucidate these molecular changes driving the fusion process. Roy’s group will use advanced microscopes to ‘watch’ the fusion process as they happen at the single molecule level. Combined with molecular dynamics simulations from the Aksimentiev group, they will infer the effect of different conditions on the fusion process.
DNA nanostructures as molecule tweezers
Due to the rapid and complex nature of the fusion process, studying membrane fusion is challenging. Roy’s team is using an unusual approach called DNA origami, pioneered by the Howorka group, to solve this challenge. Using DNA as scaffolds and tweezers, the team will induce membrane fusion in a highly controlled fashion. “To manipulate objects at the molecular level, you need tweezers and levers that are molecular in dimensions,” says Roy. “DNA nanostructures can be created with exquisite accuracy due to its ability to recognize and bind its complementary partner. This has spawned a whole new field of DNA nanotechnology. We will use nanostructures created out of DNA strands to study a problem that has nothing to do with DNA.”
Support for ground-breaking research
The Human Frontier Science Program (HFSP) is an international research grant program that supports ground-breaking research to elucidate the complex mechanisms of living organisms. The organization has a strong history of supporting pioneering research in the field of life sciences. The highly competitive research grants provide a three-year support to interdisciplinary international teams involving at least two countries.