Research
Many experimental methodologies have been perfected that enable the structure and function of proteins to be examined and controlled across a range of length scales and levels of complexity. It is now possible to manipulate proteins at the single-molecule level, and at the opposing end of the spectrum, to create detailed maps of protein interaction networks. Such advances provide a foundation for synthetic biology.
Nevertheless, cells possess much higher degrees of control over protein behaviors than one can presently achieve synthetically. One problem is that proteins commonly operate as multiunit macromolecular assemblies that range in size from 10 to 200 nm. There are many circumstances where these complexes constitute the relevant, functional building blocks of cells instead of individual proteins.
Our group has developed biosynthetic technologies that enable engineered systems of proteins to be created and interrogated with multiple levels of control and precision. Focusing on intracellular transport proteins as a model system of study, we have succeeded in integrating new biosynthetic methods with advanced single-molecule techniques to examine how structurally-defined assemblies of motor molecules communicate when transporting objects as a group.
While resolving principles governing the cooperative behavior of motors, our work has uncovered collective effects central to the regulation of intracellular transport. Our techniques also have broad utility and facilitate the creation of many types of engineered multi-protein complexes in vitro and in living cells. In this way, we are providing new tools for synthetic biologists that now make it possible to manipulate proteins at the macromolecular system level.
- ‘Singe-Molecule’ Studies of Collective Motor Transport
- Intracellular Transport Regulation in Living Cells
- Multiplexed Protein Detection and Profiling Technologies
Key Words: Protein Engineering, Synthetic Biology, Macromolecular Complexes, Intracellular Transport, Protein Profiling, Single-Molecule Biophysics |
