Despite substantial biotechnological advances in recent years, understanding how a specific molecule acts during complex biological processes remains a challenge in biomedical research. The EU-funded iSenseDNA project is focusing on developing technology that will make it possible to identify the relationship between the change in a molecular structure and its biological function.
“Previously, we only had access to snapshots of the structure of molecules, but we need to relate the structure of a molecule to its function. It's a bit like using pictures of ice skaters to learn how to play hockey. Our project involves creating an opportunity not only to learn how to play hockey, but also to understand which muscles we need to train to become better players,” explained Professor Lynn Kamerlin, who is coordinating the project at Uppsala University together with Dr Antonietta Parracino.
In iSenseDNA the use of custom-designed synthetic DNA molecules as a “translator” to detect and extract hidden information about biomolecular processes is being proposed. These “translators” will be nano-transducers based on supercoiled DNA and will be fabricated by fitting the DNA structures with specific proteins so as to control their topology and facilitate their interactions with the relevant proteins. The Biomolecular Nanotechnology group at CIC biomaGUNE, led by Ikerbasque professor and the center's scientific director Aitziber López-Cortajarena, has expertise in protein engineering and throughout the project will be tackling experimental engineering for the production of these nano-transducers and the integration of specific recognition molecules. “This project has an unprecedented, disruptive approach in biomolecular detection with the potential to completely transform medical diagnosis and treatment,” said Professor Cortajarena.
The research groups involved in the iSenseDNA project are keen to develop a technology that relates changes in the structure of a biomolecule to its function during complex dynamic processes in real time. Today, there are techniques to study the function of a molecule during a biological process, and there are techniques to study the detailed structure of molecules. However, no one has managed to link structure to function on a large scale. This makes it difficult to predict the structural changes needed to improve drug development, for example.
The project will combine computational and biotechnological methods as tools for the advanced optical analysis of biomolecules “in action”. By putting these tools together they want to develop a so-called nano-transducer, a DNA-based sensor sensitive to structural changes and capable of reading them in real time.
“This multidisciplinary project has emerged out of a collaboration between different fields and technologies with the potential to extract information about complex processes, which is difficult to do otherwise. All this will ultimately contribute to various advances in diagnosis and medical treatment,” added the coordinators.
The iSenseDNA research groups come from the universities of Uppsala, Umeå and Padua, the research centers CNR, CIC biomaGUNE, DESY and ESRF, and the company OrganoTherapeutics. The project has a total budget of approximately € 3 million and is funded by the European Innovation Council within the framework of the EIC pathfinder open call.