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Grant Application Details
- Bioengineering technology for fast optical control of differentiation and function in stem cells and stem cell progeny
Embryonic stem (ES) cells potentially could provide clinically important replacement tissue for central nervous system (CNS) disease treatment, and regenerative medicine approaches involving ES cells have been suggested for common CNS disorders. But it has been difficult to produce the right kind of replacement tissues from ES cells because the “differentiation”, or cell-type specification process, takes many days to weeks, during which time many different stimuli and signaling molecules need to be physically applied to the stem cells. This process of “stem cell differentiation” is slow, costly, laborious, variable, prone to error and contamination, and ultimately rate-limiting in the long road leading to clinical translation. We propose to develop and apply fast, inexpensive, and robust optical technologies to the fundamental problem of stem cell differentiation and regenerative medicine, with particular focus on CNS disease.
Neuropsychiatric diseases like Parkinson’s disease and major depression are leading causes of disability and death in California and worldwide. They are difficult to treat, poorly understood, and devastating for patients, families, and society as a whole. Our proposed fusion of engineering technology with clinically-inspired stem cell technology represents a unique opportunity, which we anticipate will lead not only to fundamentally new, potent, and specific therapies for diseases representing major burdens for the state, but also to engineering and medical commercial ventures that will add resources, money, and skilled jobs to the robust and growing state economy.
Publications
- Stem Cells (2011) Tracking stem cell differentiation in the setting of automated optogenetic stimulation. (PubMed: 21280159)
- Nat Neurosci (2011) An optogenetic toolbox designed for primates. (PubMed: 21278729)
- Neuron (2011) Optogenetics in neural systems. (PubMed: 21745635)
- Nature (2011) Neocortical excitation/inhibition balance in information processing and social dysfunction. (PubMed: 21796121)
- Cell (2011) Dynamics of Retrieval Strategies for Remote Memories. (PubMed: 22019004)
- Nat Neurosci (2011) Optetrode: a multichannel readout for optogenetic control in freely moving mice. (PubMed: 22138641)
- Cell (2011) The microbial opsin family of optogenetic tools. (PubMed: 22196724)
- Neuron (2011) Recombinase-driver rat lines: tools, techniques, and optogenetic application to dopamine-mediated reinforcement. (PubMed: 22153370)
- Science (2010) Cholinergic interneurons control local circuit activity and cocaine conditioning. (PubMed: 21164015)
- J Neurosci (2010) Dlx5 and Dlx6 regulate the development of parvalbumin-expressing cortical interneurons. (PubMed: 20392955)
- Nat Neurosci (2010) Ultrafast optogenetic control. (PubMed: 20081849)
- Cell (2010) Molecular and cellular approaches for diversifying and extending optogenetics. (PubMed: 20303157)
- Nature (2010) Global and local fMRI signals driven by neurons defined optogenetically by type and wiring. (PubMed: 20473285)
- Nat Protoc (2010) Optogenetic interrogation of neural circuits: technology for probing mammalian brain structures. (PubMed: 20203662)
- Nature (2009) Temporally precise in vivo control of intracellular signalling. (PubMed: 19295515)
- Nat Neurosci (2009) Bi-stable neural state switches. (PubMed: 19079251)
- Science (2009) Optical deconstruction of parkinsonian neural circuitry. (PubMed: 19299587)
- J Neurosci (2009) Sleep homeostasis modulates hypocretin-mediated sleep-to-wake transitions. (PubMed: 19726652)
- Nature (2009) Parvalbumin neurons and gamma rhythms enhance cortical circuit performance. (PubMed: 19396159)