Prospect Hill Academy
Vladimir Tkachev and Nathaniel Goble
Stanley Center for Psychiatric Research | Pan Lab
When Sybille applied to BSSP, she knew the "research I do over the summer will be impactful and challenge me to learn new things." At the Broad, Sybille was matched with researchers at the Stanley Center for Psychiatric Research to conduct cutting-edge research on Schizophrenia. This severe psychiatric disorder affects roughly 24 million people worldwide. While most drugs on the market for Schizophrenia treat symptoms such as hallucinations and delusions, these patients suffer from cognitive and sleep impairments. During sleep, brief bursts of brain activity, known as sleep spindles, occur during stage 2 of non-REM sleep and are essential for memory consolidation and cognitive function. Patients with Schizophrenia show reduced sleep spindles, which may account for deficits in both sleep and cognitive function. Past research has shown that one of the risk genes that significantly increase a patient's risk of developing Schizophrenia is a loss-of-function mutation of the CACNA1I gene, which encodes for Cav.3.3 voltage-gated calcium channels. Cav.3.3 voltage-gated calcium channels are highly abundant in the thalamic reticular nucleus (TRN), which generates sleep spindles positively correlated with learning and memory. Sybille and her partner Matthew aimed to target Cav3.3 channels with novel therapeutics and rescue their defects in vitro. By the end of the summer, they successfully characterized two compounds capable of modulating the calcium concentrations of HEK293 cells. Simultaneously, their mentors were able to show that these compounds rescued sleep spindle deficits in mice, corroborating the findings made by Sybille and Matthew. Upon reflection, Sybille says, "BSSP taught me that it's okay not to know. Before, I used to think that not knowing or understanding something meant that I just wasn't as smart, but now I know that it just means I have something new to learn."