Year 1Therapies and diagnostics that depend on differentiating stem cells may be fundamentally accelerated with a fusion of optical bioengineering and stem cell technology that we propose to develop and apply. Indeed, we anticipate that development and dissemination of this technology will lead to 1) in vitro methodology for fast reliable cell production, 2) deeper understanding of the basic science and biology of signaling in stem cells as they proliferate, differentiate, and generate phenotypically complete and stable progeny; and 3) in vivo methodology for noninvasively stimulating new cells in patients with devastating degenerative diseases.
Year 2The goal of this work has been to develop optogenetic technology for the study of stem cells. Major aims include optogenetic technology development and dissemination/distribution/collaboration with stem cell scientists. This work has progressed well, and our work (optogenetics) was recently named method of the year across all fields of life science and engineering, by Nature Methods:
Deisseroth K (2011). Optogenetics. Nature Methods, 8:26-9.
Weick JP, Johnson MA, Skroch SP, Williams JC, Deisseroth K, Zhang SC. Functional control of transplantable human ESC-derived neurons via optogenetic targeting. Stem Cells. Epub 2010 Sep 8.
Tønnesen J, Parish CL, Sørensen AT, Andersson A, Lundberg C, Deisseroth K, Arenas E, Lindvall O, Kokaia M. Functional integration of grafted neural stem cell-derived dopaminergic neurons monitored by optogenetics in an in vitro Parkinson model.PLoS One. 2011 Mar 4;6(3):e17560.
Stroh A, Tsai HC, Wang LP, Zhang F, Kressel J, Aravanis A, Santhanam N, Deisseroth K, Konnerth A, Schneider MB. Tracking stem cell differentiation in the setting of automated optogenetic stimulation. Stem Cells. 2011 Jan;29(1):78-88. doi: 10.1002/stem.558.
Year 3We have made extensive progress in developing optogenetic tools that can be used for stem cell biology. Optogenetics is a method for using light to control well-defined events within specified cells, even within systems as complex as intact behaving mammals. Broadly our project has included both using optogenetics to control the differentation of stem cells, and for controlling stem cells, their progeny, or surrounding cells in the living mammal to assess and guide function. Over the recent funded period we are pleased to report that we finally achieved the first multiple-color excitation (two separate channels of control) in mammalian brains, which will have far-reaching impact on the study of interactions between stem cells and their environment, as well as on technology used for maintaining, expanding, controlling, and studying these powerful biological tools.