Following the Signals: How A Passion for Neuroplasticity Sparked My TORC1 Research
Following the Signals: How A Passion for Neuroplasticity Sparked My TORC1 Research
How does a cell really work? How does it make decisions? How does the sum of its microscopic parts become a self-sufficient entity, which can form communities of increasing complexity, creating organs, and ultimately advanced life? To begin to understand this, we can view each individual cell as a microscopic brain, where each neuron is instead a protein, carrying a unique message to the receiver, which allows the cell to carry out tasks. In my lab, I look at different proteins and try to decipher the messages they send.
This captivation with complex systems and their inner workings has been a consistency throughout my life. My interest in science was sparked in the sixth grade, when I read a book on neuroplasticity, or the brain’s ability to rewire itself and form new connections as a means of adapting to stimuli. My initial preoccupation with the human brain turned more broadly into a deep curiosity about biological processes in general, eventually placing me where I am today, earning my PhD in Molecular & Cellular Biology in the lab of Dr. Andrew Capaldi. Unexpectedly, there’s an uncanny similarity in my fixation with the human brain, and what I research now, where I view each cell as a tiny brain, rapidly and constantly firing in response to various inputs. Through my research, I aim to answer big questions, such as, how does a cell decide when to grow?
There’s a group of proteins which form a complex, Target of Rapamycin complex, or TORC1. All eukaryotes have TORC1 in every cell, and it serves as a central hub for taking in environmental cues to regulate cell growth. This might sound straightforward-- if a cell has nutrients, or if you just ate a big meal, we have tons of resources at our disposal, so of course that means it’s a good time to grow and make new proteins, not rest. But when you take a moment to think about it, how is the cell sensing that we have enough glucose, or enough of everything else? And how can it integrate that information to activate all the other proteins that promote growth? In short, we don’t fully understand yet, but we do know that TORC1 is at the heart of it all. TORC1 is analogous to an old-timey telephone switchboard operator, constantly forwarding phone calls to their appropriate receivers, so that messages can be delivered. And despite all that we do know, this “operator” exists in a vast, interconnected web in the cell, where we have a lot of blanks left to fill in. I aim to find more puzzle pieces in the incomplete picture of how a cell coordinates growth. We have new leads that the mitochondria (the powerhouse of the cell!) communicates closely with TORC1, but we’re not yet sure when and how. I’m excited to be involved in this project because it allows me to explore many different aspects of biology, while also engaging my creativity in formulating new hypotheses about previously unknown relationships.
However, as fascinating as the cell’s mechanisms are when everything is functioning correctly, it’s equally important to understand what happens when those systems break down. Returning to the analogy from before, it would be as if the switchboard operator just started pushing random buttons. This would make all the calls reach the wrong receiver at the wrong time. And as you can imagine, things become quite dangerous in the cell. In the context of a cell and TORC1, that’s what often leads to cancer. Tumors are typically due to a couple of unlucky mutations that collectively break a cell’s regulatory mechanisms for fine-tuning growth. When the inputs don’t correspond to the correct outputs, we have a bad cell that constantly divides and eventually invades healthy tissue. And proper growth regulation is so important that roughly 30% of cancers involve TORC1 pathway mutations. Therefore, it’s critical that we understand how TORC1 works, so that we can develop improved cancer therapeutics. While my work doesn’t involve creating the drugs directly, I’m fortunate to be at the forefront of uncovering answers to the complex questions that have challenged science and medicine for decades. For me, science is most meaningful when I can contribute to solving intricate problems, even if those solutions exist on a microscopic scale.