Circuit mechanism of STXPB1-encephalopathy interrogated using human brain organoids
Awardee: Christopher Makinson
Institution: Columbia University
Award Amount: $71,658
Funding Period: February 1, 2021 - January 31, 2022
Summary:
Mutations in the gene STXBP1 are associated with multiple diseases ranging from intellectual disability to severe epilepsy and developmental delay. To understand how STXBP1 mutations impair brain development we will generate 3D cellular structures derived from patient cells, called brain organoids, that resemble in many ways the developing human brain. Since previous studies have shown that STXBP1 is important for chemical signaling between brain cells, we will examine how STXBP1 mutations affect excitatory and inhibitory chemical signaling within brain organoids. We will also apply novel high throughput approaches to measure the activity of many brain cells at one time in order to gain insights into the effects of STXBP1 mutations on cellular network activity. These approaches will allow us to determine if STXBP1 deficiency has more pronounced effects on certain parts of the brain. Importantly, we will leverage these approaches to look at multiple time points to clarify how impairments evolve throughout early development and contribute to disease. Support from this pilot grant will allow us to establish a novel human cell model of STXBP1 encephalopathy, develop novel approaches to measure cellular activity in human brain organoids, and facilitate efforts to develop novel treatments for STXBP1 encephalopathy.