Thesis Christ: Mini Molecules and an Iron Rainbow

On Reed’s grey and rainy campus, most students delight at any rainbows they come across — but biochemistry Spring/Fall senior Dorothy Cheng wishes she saw them less. Cheng is studying the molecule nicotinamide adenine dinucleotide (NAD). Despite its small size, NAD plays an important role in human biology. However, the protein she is using to investigate NAD easily binds with iron, creating a beautiful rainbow of colors that has complicated Dorothy’s thesis research. 

Before we got to the fun colors, Dorothy explained to the Quest why she was studying NAD. “NAD is a molecule that’s very important to metabolism in basically all living organisms… it’s important for a lot of enzymatic activities, you basically can’t live without it. So understanding how this molecule is regulated in living organisms becomes very important because we can’t have too much of it and we can’t have too little of it. The protein I study is an NAD biosynthesis regulator, which means that it regulates how much energy is produced in bacteria.”

The main goal of her thesis is to figure out a three dimensional structure of this protein. To do this, she utilized X-ray crystallography, a process which can create an image by using the diffraction patterns of X-rays. Although this process was eventually successful, it was initially complicated by the presence of an iron ion, which the literature had suggested would instead be nickel. The iron ion caused her to see a variety of bright colors. “I’ve seen so many colors in protein. It’s been purified purple when the iron is oxidized. It’s yellow in another species when it’s not oxidized. And then because I have to perform a lot of experiments that have something to do with… calculating iron content, I have a lot of colorimetric assays, which gives me many different colors… I’ve seen green in one of the solutions that we use to measure any measure of iron concentration. And then some of my protein is purple. Another method of measuring protein concentration gives me the blue and more methods of measuring protein concentration gives me bright purple. So I’ve seen pretty much all the rainbow colors.” 

Although all of the rainbow colors might seem fun to an outsider, Cheng did not expect to see them in a protein lab. “Proteins are usually colorless. And I’m used to seeing transparent and colorless things.” But despite these colorful setbacks, Dorothy successfully obtained her protein structure and is now in the final stages of her thesis.

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