Investigating Diabetes with the SURE Award

28 Sep

This post is written by UHPer and SURE Award winner Mailin Li.

Mailin Li

Mailin Li

Sometimes, I feel like I’m going crazy. There I am, day after day, in a confined, temperature-regulated space with no natural lighting, pipetting clear liquids into clear liquids and hoping something miraculous occurs.

The topic I’m investigating is amyloidosis, the aggregation of the amylin protein in forming the plaques that lead to diabetes. Diabetes is defined as the insufficient secretion of insulin, a glucose regulating hormone, by beta-cells in the pancreas or decreased ability of insulin in regulating blood glucose, that results in glucose buildup in the blood. Amylin is a protein co-expressed and co-secreted with insulin. In the initial stages of diabetes, the body compensates for the perceived insulin shortage by increasing demand; however, because amylin levels are raised in parallel with that of insulin, excess amylin monomers aggregate to form insoluble amyloid plaques, which eventually kill the islet and cause oxidative stress to the surrounding area. This is where I come in.

Oxidative stress is when the production and presence of reactive oxygen species in a biological system make it unable to detoxify the intermediate produces and resulting damages. In Type II Diabetes, when amylin aggregates into fibrils, the protein undergoes conformational changes that release free radicals into the cell. The released radicals then bind to lipids, other proteins, and DNA itself, leading to the malfunction of these cellular components.

My experiments focus mainly on manipulating the aggregation rates of amylin in vitro with a variety of substances and conditions to simulate what amylin would do in the body, i.e. in vivo. Some of the components we add are oxidizing agents such as bathocuproine or reducing agents like glutathione. I measure the results using a variety of protein assays, detecting for apoptosis (cell death), toxicity analysis, and the kinetics of aggregation using spectroscopy. The goal is to figure out where these radicals are coming from, establish a causal relationship between oxidative stress and amyloidosis, and hopefully prevent aggregation or epigenetically reduce the effect of its product. So far, we’ve narrowed down two forms of copper, Cu2+ and Cu+, as a source of the radicals that feed the renewing cycle of cytotoxic H2O2 generation that leads to oxidative stress. We still don’t know the specifics of how this system works, though.

Hence, why I’m pipetting clear liquids into clear liquids. Again and again and again.

Like all things worth pursuing, science is often an unforgiving subject; tiny mistakes amount to huge percent errors, failure is more the norm than success, and repeating the same experiment often gives varying results. This is discouraging, to be sure, but because I love science and I love what I do, I keep going.

The UHP Sure Award is the perfect venue for inspiring and encouraging potential researchers and scientists to engage in what they do best–think and play.

The foundation of the UHP Sure Award isn’t based on monetary support, but rather the principle of “You have an idea? Hm. That’s interesting. Go forth and explore;” it’s based on the belief in a student’s ability to channel his curiosity into independent discovery. I’m lucky the UHP fully supports the ramblings of my mind, even if sometimes I don’t fully understand it myself. And on that note: thank you so much Liz and Catherine for being the scaffolding holding up my sanity through the jungle of paperwork and deadlines. And thank you Dr. Jeremic for believing in me even when experiments just refused to work, and allowing me to work in your lab as a undergrad freshman.

People often see science as strict and stagnant, when really, it’s the study of the magic that keeps people alive. This magic is  dynamic and creative in its fluidity, simple in its efficiency but admirably complex. For me at least, there’s no greater mystery or reward.

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