A Matter of Perspective

In molecular biology, it's all about scale. The size of a tissue inside your body, the size of a cell, the size of a protein inside of a cell, the size of a small piece of DNA, the size of a small signaling molecule...the range is pretty impressive. Traditional biology was done by amateurs, if you will; people with a curiosity for the world around them who simply observed the way things work. Biology today is surprisingly not that different, since our goal is still to figure out how things work. However, because of the increasingly minute scale of the systems we study, the issue becomes how can we be an observer?

Much of the work that I do on a day to day basis involves manipulating biological molecules in such a way that I can "see" them. For instance, I can look at my cells under a microscope, but I can't see their DNA. How do I know that it's there? What does one have to do to actually "look" at DNA? Several cute tricks that exploit the properties of DNA have been developed over the years which, when combined, allow me to examine DNA (Sorry biologists, this is sort of a rundown for people who have no idea what we do). For instance, DNA has an overall negative charge which is proportional to the length of the DNA itself. Therefore, you can expose DNA molecules to an electric field and they will separate based on the length of the molecule. By putting the DNA into a gel matrix, I can isolate DNAs of different sizes. This is a good separation technique, but it still doesn't allow me to "see" DNA. However, I can take the gel and expose it to a chemical called ethidium bromide which fluoresces under UV light. The chemical will seep into the DNA and then when a picture of the gel is taken with UV light exposure, the DNA will fluoresce brightly! Hooray, I can see! The gel in the post is a very pretty picture of an enzyme titration that I use to get mononucleosome DNA.

Even the boring stuff that I do everyday is pretty amazing when I stop and think about what it allows me to accomplish. However, one of the next big areas in biology is using all of the imaging technology that we've developed over the past half century and using it to actually observe molecular biology. Tricks are cool and everything, but seeing is believing, or so they say. Instead of isolating proteins in massive amounts and testing their interactions in a test tube with other purified proteins, wouldn't it be much more informative to track different proteins in a living cell? And if I wanted to see how a transcription factor finds a piece of DNA, instead of crosslinking the two and purifying them, wouldn't it be great if I could watch that transcription factor scanning DNA in real time? With improved fluorescent microscopy techniques, this is becoming possible. It's definitely the future of biology and exciting, especially for those of us who are observational biologists at heart.