Proteins in Motion: Measuring Disorder and Interactions at Single Molecule Level

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Understanding life at molecular level is one of the great challenges in modern science. This will bring major benefits to society, including new ideas for better drugs and therapies against diseases, the design of bio-mimetic nanotechnology and the development of innovative medical imaging methods. Gradinaru biophysics research laboratory is developing advanced optical detection techniques for precision measurements of conformation and interaction dynamics of individual biological molecules. Single-molecule methods have become popular in biology because they can capture molecular states and processes without loss of information due to ensemble averaging. We designed and set up microscopes that record multiple optical properties simultaneously though intelligent detection and data analysis of single photons emitted by single fluorescent probes. This very powerful and sensitive equipment will be further improved and applied to the study of several dynamic protein complexes. We will investigate how rationally-designed small-molecule drugs can inhibit the cancer activity of STAT signalling proteins and will characterize structural fluctuations in disordered proteins in order to understand their role for biological activity. In the long term, single-molecule approaches will also be applied to complex allosteric membrane proteins, such as the cyclic nucleotide gated channels, to determine the role of aggregation in signal transduction and the relationship between ligand binding, conformational dynamics and channel activation. Corroborated with data from our collaborating groups, this ambitious research plan could lead to new therapies against blood cancers, heart and neurodegenerative diseases affecting the Canadian population.