Grant: Discovery Grants Program - Individual

The proposed research focuses on the structural and functional dynamics of the cellular machinery that is responsible for the translation of genetic information into functional proteins, a process called translation. Translation takes place at the ribosome, a large macromolecular complex, which in a complex and precisely timed fashion interacts with several additional protein factors to achieve the fast and efficient protein synthesis observed in the living cell. To study the functional and structural dynamics of translation factors on the ribosomes; a purified in vitro translation system will be studied applying a multidisciplinary approach combining techniques ranging form classical biochemistry and fluorescence spectroscopy, to computational techniques such as molecular dynamics calculations. The detailed understanding of the dynamical properties and mechanisms inherent to the processes taking place in macromolecular assemblies are crucial for a wide variety of applications. The ribosome is a particularly relevant and interesting model system. It is the site of protein synthesis and the target for numerous antibiotics and rational drug design projects. Furthermore, the proposed program will strongly contribute to our understanding of the principles behind protein-RNA interactions as well as their folding and miss-folding. Understanding the dynamical properties in macromolecular assemblies will also have a strong impact on our knowledge of how protein and RNA functions together and will pave the road toward the development of macromolecular nanomachines setting the stage for biomolecular engineering.