Tenzin Paljor

The body responds to stress or excitement by releasing adrenaline, which helps the heart beat faster and more forcefully. This happens through a process that increases the flow of calcium ions into heart muscle cells through specialized gateways called CaV1.2 calcium channels. Scientists originally believed that adrenaline was released due to the activation of a protein called protein kinase A (PKA), which would directly modify these calcium channels to enhance their activity.

However, recent research has suggested that adrenaline does not act directly on the calcium channel. Instead, a small protein named Rad is the key target of PKA. Rad usually inhibits the CaV1.2 calcium channel and limits the calcium flow, acting like a brake. When PKA is activated, it modifies Rad, causing it to detach from the calcium channel, which increases calcium entry and boosts heart contractions, which allows for better and more efficient blood circulation. In heart failure, however, calcium signaling often becomes disrupted, leading to poor heart function. Understanding the proteins that regulate calcium entry, like Rad, may lead to new therapies that improve heart performance with fewer side effects than current treatments.

In my project, I will investigate how adrenaline signaling affects protein interactions around the CaV1.2 calcium channel in heart cells. I will use a technique called proximity proteomics, which combines TurboID-based biotinylation, a method for tagging nearby proteins, to identify which proteins are physically close to the channel before and after activation of PKA, a key enzyme triggered by adrenaline. By mapping this dynamic network, I aim to uncover not only known regulators like Rad, but also previously unrecognized proteins that may influence calcium channel activity. Understanding these interactions is crucial, especially because disruptions in calcium signaling are a hallmark of heart failure, where the heart becomes too weak to pump blood effectively. By identifying new players in this pathway, this research aims to help lay the groundwork for more targeted therapies to improve heart function and treat conditions like arrhythmias and heart failure.