Grant Award Details
To address these deficiencies by developing reliable and consistent organoid differentiation methods for producing 3-dimensional cortical structures containing both excitatory and inhibitory interneurons. We will also use lineage-tracing and electrophysiological recording methods to investigate the ability of organoids to establish cortical columns defined by the interconnection of groups of neurons derived from a common progenitor.
Grant Application Details
- Organoid Modeling of Human Cortical Microcircuits
The proposed studies will develop three-dimensional cell culture methods for creating human brain neural circuits for disease research and drug discovery.
The proposed research will develop a new research platform for studying how neurons in the human brain function, how neurological disease subverts this activity, and how we might find new therapies.
Major Proposed Activities
- Develop robust and reliable methods for creating three-dimensional organoid ("mini-brain" ) structures from human pluripotent stem cells.
- Measure the ability of neurons within mini-brain structures to form functional connections with one another that resemble those seen in the human brain.
- Determine how mini-brain neurons are organized at a larger network level to better model the normal and pathological activities of the human brain.
Neurological diseases are among the most debilitating medical conditions that affect millions of Californians each year, and many more worldwide. Few effective treatments for these diseases currently exist, in part because we know very little about the mechanisms underlying these conditions. Our proposed studies will develop an innovative cell culture platform to create a facsimile of human brain circuits that will enable us to better understand disease pathologies and discover new therapies.
- Immunity (2017) 25-Hydroxycholesterol Protects Host against Zika Virus Infection and Its Associated Microcephaly in a Mouse Model. (PubMed: 28314593)
- Cell Rep (2017) Self-Organized Cerebral Organoids with Human-Specific Features Predict Effective Drugs to Combat Zika Virus Infection. (PubMed: 29020636)