Rebecca de Frates

Voltage-gated calcium channels are molecules present in many cell types that regulate calcium influx by opening upon membrane depolarizations. Their function influences many cellular processes including proliferation, migration, neurotransmitter release, and gene expression.

Recent studies have implicated variants of voltage-gated calcium channel genes with a number of psychiatric disorders, including schizophrenia and bipolar disorder. We hypothesized that calcium influx deficiencies may play a key role in a number of psychiatric phenotypes. We surveyed recent data from exome sequencing and genome-wide association studies for coding variants in 11 genes that encode for the alpha subunit of voltage-gated calcium channels, and analyzed a subset of these variants in three genes that had a significantly higher rare variant burden in cases versus controls (assessed empirically by permutation of case/controls status). Subsequently, we introduced changes in the coding sequences of these calcium channels with reference to existing cDNA clones and are pursuing functional studies using the whole-cell patch clamp technique to assess the impact of coding variations on the channel function.

The results of this study will yield important insights into the roles of calcium channel variants in the molecular pathophysiology of not only schizophrenia, but other psychiatric disorders such as bipolar disorder.


PROJECT: Missense Variants of Voltage-Gated Calcium Channels Implicated in Schizophrenia

Mentors: Jen Pan and Colm D’Ulshaine, Stanley Center for Psychiatric Research

Rebecca de Frates<br />

It’s not just the world-class laboratories and cutting edge research that make the Broad Institute stand out, but the community. The Broad brings together talented students from diverse backgrounds with brilliant mentors who support us in everything we do. I don’t think the group dynamic that exists here can be found anywhere else.