8/08/2009

Picking a First Lab Rotation

This afternoon I began the long and meticulous research process for finding a lab for my first rotation. With one month until classes start at Penn, now is a good time to start looking for rotations, as was recommended by the newly appointed Chair of my sub-division at Penn - Developmental, Stem Cell, and Regenerative Biology (DSRB).

I initially chose DSRB as my sub-division within CAMB because of several reasons, which include my undergraduate research projects, my fascination with stem cells, and my strong interest in signaling pathways, especially Wnt signaling.

My heightened interest in Wnt signaling stems from a course I took at Rutgers in my final semester named "Genetic Regulation of Development and Cancer". The middle segment of the course, taught by Howard Hughes Medical Institute fellow Dr. Ken Irvine, focused on the Wnt signaling pathway. Dr. Irvine is no ordinary scientist, however; he was a graduate student at Stanford in Dr. Eric Wieschaus's lab when he won the 1995 Nobel Prize in Physiology or Medicine (along with Christiane Nusslein-Volhard) for their work in Drosophila embryonic development. Despite his affiliation with a Nobel Prize-winning lab, Dr. Irvine is one of the most humble researchers one can ever hope to meet. It was only by satisfying my innate curiosity that I even found out that Dr. Irvine worked as a graduate student with Dr. Wieschaus.

The Wnt signaling pathway is active in many types of organisms and in many kinds of cells. Because the pathway also plays a role in cancer biology, as it is composed of both tumor suppressor genes and oncogenes, it remains active even after development. The pathway operates as a two-state model, which means it is either activated or inactivated.



On the left is a schematic that shows the canonical Wnt signaling pathway in an inactivated state. Without the Wnt protein attached to the intra-membranous Frizzled protein, the transcriptional activator beta-catenin is bound by a three-protein complex of GSK3, APC, and Axin, whose combined function is to phosphorylate beta-catenin. Once phosphorylated, beta-catenin is targeted for degradation, which maintains low levels of the protein within the cell. The result is the transcription factor TCF actively repressed by the Groucho protein.

On the right is a schematic that shows an activated canonical Wnt signaling pathway. The Wnt protein binds to Frizzled, which causes the protein Disheveled to detach from the Frizzled domain within the cell. This newly freed Disheveled protein attaches to Axin, which causes the three-protein complex to disassociate. The result is a released and non-phosphorylated beta-catenin protein, which localizes within the nucleus. Beta-catenin competes with Groucho and initiates TCF, causing transcription of targeted genes.

The reason why I'm so intrigued in the Wnt signaling pathway is because it functions in my two favorite aspects of cell and molecular biology - embryonic development and cancer development. As I stated above, I am assigned to the DSRB sub-division, but one of the great things about Penn is that you are allowed (and even encouraged) to do one of your rotations in a sub-division different from the one you're registered in. When I heed that advice, which I will later on in my first year at Penn, I will almost certainly choose a rotation in the cancer biology sub-division. And since the Wnt signaling pathway is implicated in the physiology of both embryonic development and cancer development, I could easily do rotation projects in each sub-division that are both focused on Wnt signaling.


The Wnt signaling pathway
in cancer development


As expected, Penn has several researchers whose work focuses on Wnt signaling in some capacity. My preliminary list of rotation labs is 12, and three of the labs on my list conduct research on Wnt signaling - Dr. Edward Morrisey, Dr. Peter Klein, and new DSRB Chair, Dr. Sarah Millar. These three researchers all received 4-stars in my own rating system, and their labs will be the first three I contact.

Choosing a rotation lab is one of the most important decisions a graduate student must undertake. One of the three/four rotation labs will ultimately be the lab where a graduate student will conduct his/her dissertation project in, so you must choose each rotation lab as if it has a really good chance of becoming your thesis lab. I'm still in the early stages of my search for my first rotation lab, but having a strong interest in Wnt signaling allows me to focus on specific researchers whose work matches my interests. I definitely want to branch out my research endeavors in my first year at Penn, but in order to ensure the smoothest transition to graduate life possible, I figure it's a good idea to focus on initial labs that share the same passion for Wnt signaling that I do.

Fellow Penn (and non-Penn) graduate students - what are some of your rotation experiences? I encourage you to share your advice and experiences in the comments.

Cheers,

Mike C.

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