Francesca Tomasi received her B.A. from the University of Chicago and currently researches tuberculosis drug targets in search for novel antibiotics.
Proteins are essential components in all forms of carbon-based life, capable of serving just about every function imaginable. From providing physical structure to a cell, to orchestrating complex metabolic networks, our bodies need hundreds of thousands of different types of proteins to survive.
So how do we study them? To begin, scientists typically need to isolate a protein of interest. For example, say someone wants to investigate a bacterial protein as a new drug target. They want to isolate that molecule and test whether different drugs successfully bind to and inhibit its function.
To do so, scientists use SDS-PAGE gel electrophoresis, a popular technique that allows the separation of biological molecules.
Say you have a massive box filled with knotted ropes, but you just want to take out a single shoelace from the box. If you were looking for a specific, 15” shoelace, how would you distinguish it from a similar-looking one that’s longer or shorter if they are all knotted up? You would have to dump the box on the floor, detangle its contents, and pick out your shoelace.
Proteins exist in their own sort of knotted mess, complex three-dimensional conformations that render them uniquely capable of carrying out a very specific process. So just like it’s easier to find a specific string in a tangled mess after untangling and sorting everything out, it is easier to pick out a protein of interest by “untangling” all the proteins in a solution and sorting them out by length.
In SDS-PAGE, proteins are linearized by a detergent called SDS (which stands for sodium dodecyl sulfate) that also gives them a negative charge. Once proteins are injected into a gel (the starting point of this time-lapse video), an electric current is turned on, which allows them to travel across the gel. Larger proteins require a larger “pull” to move than smaller ones, so everything moves at a different rate down the gel.
A researcher knows the size of a specific protein of interest by studying its genetic code and the amino acids that make it up; it is therefore easy to pinpoint its location on a gel, using a template ladder (the left-most lane in this video), which acts as a size key.