Department of Biochemistry
A Memo From Millennial Kinases to the Lost Generation: “We Are Not So Lazy After All!”
Src and Abl are two non-receptor Tyrosine kinases that have similar structures but different regulatory mechanisms. Kinases are enzymes that phosphorylate Ser, Thr and Tyr residues by transferring a phosphate group from ATP. Phosphorylation often functions to turn a protein “on” or “off,” and plays a central role in cellular communication. Uncontrolled kinase activity leads to uncontrolled cell growth and ultimately cancer making kinases important drug targets.
In order to gain insight into the evolution of kinase regulation, we resurrected common ancestors of Src and Abl, and then Src, Abl and the Tec and Fer families. We manipulated various regulators, such as myristoylation for Abl and tail phosphorylation for Src, to get quantitative information on the distinct regulatory modes of the modern enzymes. We then used the same methods on the ancestors in order to understand the evolution of regulation.
Starting out in the Kern lab, I was like most undergrads; I was nervous, I had little to no clue what was going on during the first few lab meetings, and I dedicated my entire daytime to learning new lab skills and perfecting them. Fortunately, I had a mentor who was very understanding and willing to help me learn. Once I felt comfortable with the basic skills, I then focused on getting to know “my” proteins on a deeper level, as this is vital for understanding the question we are trying to answer. I slowly transitioned from being excited about or disappointed by the simplest of experiments — also known as being naïve— to being accustomed to the unexpected twists I encountered during most experiments — that is, improving my problem-solving skills. As for the science I partake in in lab, it involves two human tyrosine kinases: Src and Abl. Kinases take part in myriad cellular activities and so, are tightly regulated in the cell, which means that uncontrolled kinase activity can lead to cancer. In lab, we manipulate the various allosteric regulators to gain insight into the differential regulatory mechanisms of Src and Abl. We also use resurrected ancestors of Src and Abl to study the evolution of kinase regulation.
My experience in lab has been great so far and the Bauer Undergraduate Summer Research Fellowship has contributed profoundly to my experiences this summer. The Bauer Fellowship has allowed me advance my current project without the distractions of having to take classes or work other jobs. As a rising senior, being a Bauer Fellow also meant having the opportunity to start thinking about and gathering data for my thesis. Because one of the requirements for the Bauer Fellowship was to give back to the community in some way, I was also able to get to know some of the other fellows as we plan for the coming academic year. Overall, this summer has truly been a valuable experience and I am grateful to have had the support of the Bauer Fellowship.