It’s taken me three weeks, but I think I’m finally ready and able to explain what it is I’m actually doing in the lab this summer. And let me just say, it’s pretty awesome. Every paper I read adds another layer to the gorgeously complex and utterly menacing portrait of breast cancer in my mind. Every Western blot I’ve completed, though black, white, and often smeary, brings color and clarity to my understanding. And so, I’m going to do my best to impart my shaky and rapidly growing knowledge unto you, whom I have probably forced to read this.
I work in the Pendergast Lab, and while everyone has their individual projects, we are centered on the theme of tyrosine kinase signaling in breast cancer. Kinases are proteins that act by moving a phosphate group from ATP to another protein in the cell. This means that they essentially function as “on/off” switches in the cell. Depending on which proteins they activate, they can be seriously powerful cancer agents. For example, many are responsible for switching “on” the proteins that regulate cell growth and development, as well as cell to cell adhesion, all of which are important aspects of cancer development. Thanks to the hard work of those before us, we’re aware of the key players in this scheme, but we have our eye on one particular kinase that we think might be the oncogenic mastermind of triple-negative breast cancer cells.* That is, it is believed to transduce a variety of signals that cause cells to adopt a Cancer Stem Cell (CSC) phenotype, which is particularly dangerous because CSCs are believed to be the cause of resistance to therapy. It’s up to me and the graduate student I’m working with to more clearly define the relationships between this central kinase and its many downstream effectors. Like detectives using string and photos on a corkboard to visualize and unearth a sequence of events, we use loss and gain-of-function experiments and various assays to construct a cause-and-effect illustration of exactly how things happen in the breast cancer cell. Western Blotting, our scientific bread and butter, allows us to detect just how much of each protein is present under various conditions so as to more clearly characterize their roles and relationships in the cell. Also important to this equation is the localization of each of these proteins, as they might be harmless in the cytoplasm and villainous in the nucleus, or vice versa. By tagging them with fluorescent antibodies (essentially making them glow) we can visualize their battle stations at the various stages of cancer.
This project is challenging to say the least, but it’s also terribly exciting. I’m so glad that I get to contribute my two cents– or at the very least my several amateurish blots and endless questions.
*I am fully aware that proteins are not sentient, but it’s easier and a lot more fun to explain it this way.