The Pursuit of the Insulin Signaling Pathway

This summer, I’ve been working full time in the Obesity and Metabolism Lab, within the Human Physiology Department at the University of Oregon. The lab as a whole is pursuing several research objectives related to how human health is impacted by obesity and high fat diet (HFD), which affect more people today than ever before. The objective of my research is to understand how insulin-resistance, the hallmark symptom of type-II diabetes, develops as a result of obesity and HFD.

Insulin is a hormone produced in the pancreas that is delivered throughout the body, signaling cells when they need to take up glucose from the bloodstream for energy. Cells respond to this communication with a so called “signaling cascade.” Insulin binds to a receptor protein at the surface of the cell, sending the signal via more protein interactions inside the cell, toward the nucleus. This eventually leads to new proteins being made from the cell’s DNA, which will help with glucose uptake. These pathways can be very complex, and have “cross-talk” with other pathways for different cellular functions. If the exact mechanisms of the entire insulin signaling pathway where known, then it would be much easier to see exactly where diabetes causes a disruption, and potentially develop better treatments or a cure.

My project looks at just one protein in the insulin signaling pathway, called phosphatidyl inositol-3-kinase and one of its regulatory subunits called p55a. I’m looking to see if fat cells (called adipocytes) behave differently when p55a is upregulated. When there are relatively high amounts of this regulatory subunit, does the cell become more sensitized to insulin, or less? Does it take up glucose better, or worse? These observations will hopefully allow me to infer how p55a modulates PI3K’s role in the insulin signaling pathway.

What did you learn working in the lab?

As my first real research experience, I’ve learned a lot about the process of laboratory work. The biggest thing I’ve noticed so far is that my experiment isn’t moving as quickly as I had anticipated. Much of my time has been spent troubleshooting. I’ll try a procedure, it won’t quite work as it should, and I’ll have to re-trace my steps to determine how I can optimize the process or correct problems. It seems like each week something new arises that needs to be re-done two or three times. For example, I’ve been growing mouse cells in flasks which I will use for my experiment once they have “matured” into adipocytes. This process requires about two weeks of careful cell maintenance, and I’ve had to start over once because they didn’t develop properly. The other researchers in my lab have told me that they, too, still spend a lot of time troubleshooting, and that being able to recognize necessary adjustments is a crucial skill for a scientist to possess.

Life as a Scientist

My day-to-day life as a research scientist is quite different than it was in all my previous jobs. The work is very much self-supervised, and I have a freedom to plan out my daily tasks in an order that I choose. On the other hand, certain time-sensitive procedures dictate my schedule very strictly, such as changing out the growth media for my cells. This needs to be done every three days, or the cells can die. When juggling multiple projects such as this, I’ve found that making a specific schedule is key. I often write out game plans which allocate time to each of my required tasks for the coming days. This keeps me working efficiently, without losing sight of the broader goals for my ten-week fellowship.

Working as part of a lab team is my favorite part. Every day, I’m learning valuable new skills from my co-workers and asking them interesting questions. They’ve all been very accommodating and willing to teach me. We’ve discussed all kinds of topics, ranging from protein function to the application process for graduate school. The lab is an intellectual environment in which I’ve definitely enjoyed spending my summer.

Shawn Melendy is a junior majoring in Biochemistry at the University of Oregon in Eugene, OR. He is a 2017 APS STRIDE Fellow working in Dr. Carrie McCurdy’s Obesity and Metabolism research lab at the U of O. Shawn’s research is funded by the APS and a grant from the National Heart, Lung and Blood Institute (R25 HL115473-01), as well as Dr. McCurdy’s grant from the NIH (R01 DK095926). After finishing his bachelor’s degree at Oregon, Shawn plans to attend graduate school and earn a PhD. in biochemistry, pursuing a career as a research scientist.

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