Modeling neurodevelopmental disorders with genetically defined human neurons

2014 Seed Grant
Helen Bateup, Ph.D.
Dept. of Molecular and Cell Biology
University of California, Berkeley

Model experimental systems, such as mice, are often used to investigate the mechanisms of neurological disease. However, it would be ideal to examine the causes of disease and test potential therapeutics in a human cellular context. To achieve this we are utilizing a “disease-in-a-dish” approach based on state-of-the-art technology to transform skin cells obtained from patients into human brain cells, called neurons. These neurons retain the genetic information of the patient from which they were derived allowing us to investigate disease mechanisms in a clinically relevant context. We propose to use this system to investigate how mutations in genes that cause the autism and epilepsy-related disorder Tuberous Sclerosis Complex (TSC) affect the ability of neurons to communicate with each other, and how altered neuronal communication leads to imbalanced neural network activity. In addition to revealing the causes of brain dysfunction in neurodevelopmental disorders, our future studies will test the ability of potential therapeutics to restore normal patterns of activity directly in patient-derived neurons.

Other Grants

Lindsay M. De Biase, Ph.D., University of California Los Angeles
The Role of Microglial Lysosomes in Selective Neuronal Vulnerability
Synapses, the sites of signaling between neurons in the brain, play essential roles in learning, memory, and the health of neurons themselves. An enduring mystery is why some neurons are…
How the Nervous System Constructs Internal Models of the External World
As animals navigate their environments, they construct internal models of the external sensory world and use these models to guide their behavior. This ability to incorporate ongoing sensory stimuli into…
Xiaojing Gao, Ph.D., Stanford University
When Neural Circuits Meet Molecular Circuits: Quantitative Genetic Manipulation with Single-cell Consistency
Cells are the building blocks of our bodies. We get sick when the cells “misbehave”. The way modern gene therapies work is to introduce genes, fragments of DNA molecules that…
Rafiq Huda, Ph.D., Rutgers University
Conducting the Orchestra of Movement—Functional Role of Striatal Astrocytes in Health and Disease
Movement requires coordinated activity across a large brain-wide network. The striatum is a particularly important part of this circuit; it integrates motor-related information from many distinct brain regions to regulate…