No List (Data Mining)
New tools from plant transcriptomes, for optical control of biological processes
Project Contact: Ed Boyden, MIT
In many neural disorders, specific kinds of brain cell are compromised, throwing into disarray the critical computational functions mediated by the brain. The ability to understand how the cells of the brain work together, and how they are corrupted in neural disorders, requires the ability to selectively perturb biological processes in specific cell types, observing the resultant impact on brain function. In order to accomplish this, over the last half-decade, we have developed a series of molecular tools that enable neurons to be activated or silenced by different colors of light. We have distributed these tools to hundreds of labs around the world for use in analyzing brain circuits, and we are prototyping novel therapies based on these tools for ultraprecise correction of pathological brain processes.
Molecular tools that enable optical control of biological processes, often called “optogenetics,” are largely based on proteins encoded for by genes from natural species of algae, fungi, and archaebacteria. These proteins respond to light by altering signaling processes within cells in which they are heterologously expressed, such as neurons or other cell types. In collaboration with the OneKP project, we are screening plant transcriptome data for genes that encode for novel light-sensitive proteins that could serve as such optogenetics reagents. We are synthesizing the genes that emerge, testing the genes by expressing them in heterologous systems, and mutagenizing residues in these genes to see what new properties emerge. As an example of some of our earlier work, in January 2010 we published a paper in Nature describing a series of protein-based reagents from archaebacteria and fungi that enable powerful, multi-color silencing of neurons in the brain, and we also present results from mutating key amino acids of these proteins (Chow et al., 2010). We hope that our collaboration with the OneKP project will yield a diversity of new tools important for bioengineering, medicine, biology, and neuroscience.
Finally, we hope to arrive at a genomic and ecological perspective on how the properties of these molecules arise in an evolutionary sense, understanding how organismal properties lead to specific kinds of light-sensitive protein functionality.
REFERENCES
Boyden, E. S. and Chow, B. Y. (2010) "Defining an algorithm for inventing from nature." Technology Review. 1/19/2010.
Chow BY, Han X, Dobry AS, Qian X, Chuong AS, Li M, Henninger MA, Belfort GM, Lin Y, Monahan PE, Boyden ES. High-performance genetically targetable optical neural silencing by light-driven proton pumps. Nature. 2010; 463(7277):98-102.
Han X, Boyden ES. Multiple-color optical activation, silencing, and desynchronization of neural activity, with single-spike temporal resolution. PLoS ONE. 2007; 2(3):e299.
See Also: http://syntheticneurobiology.org/