Wednesday, March 31, 2010

My Research Explained: The Basics of DNA

It has been almost a year since my last Research Explained post, and I promised at the beginning of the year that I'd do some. Determined not to let it get to the one year point, and armed with some free time, I've decided to provide the next phase of insight into my research. The first wave of posts was about the physics of my research:
  • What are optical tweezers
  • How we take data
  • How unzipping DNA works
  • What exactly my project is (DNA mapping)

This next phase is going to go into the biology of my project. And I'm going to start with several key features of DNA that I use to my advantage in my project. DNA is a very useful material. In Molecular Biology, scientists can use it to detect how proteins and chemicals affect cellular processes. In Materials Sciences, there is a new fad called DNA Origami where 3D structures are made by cutting and folding DNA completely naturally. In my research, I use DNA to paste together specific sequences to perform my unzipping experiments. Let me start with at the beginning...

Everyone knows what DNA is, or at least they've heard of it. Truth is, the general population probably understands very little about DNA. Everyone knows DNA is inside us and is the genetic makeup of our body, but do people actually know what that means? What exactly is a genetic code? Why is DNA a double helix? Why is it so magical? Truth is science has answered a lot of these questions but there is still a lot to learn.

DNA is a double helix of molecules that come together to make a polymer (like plastics but organic). It has a very defined structure. DNA is made up of phosphate molecules that link together deoxyribose, a sugar molecule, to form the backbone of DNA. Attached to each deoxyribose can be one of four base molecules (Adenine, Cytosine, Guanine, and Thymine) and this combination of molecules is known as a nucleotide. Hence the name Deoxyribo Nucleic Acid (oh yea DNA is an acid).

DNA can be double stranded or single stranded. Single stranded DNA is like very floppy and can be thought of as a string of paper clips (in physics it is modeled like the freely-jointed chain). Double stranded DNA is less floppy and can be thought of more like a wet noodle (in physical terms it is known as the worm-like chain). It is formed due to interactions between bases. Each base can bind to one other base, in some circumstances bases can bind to anything but we won't get into that, and so for two strands to come together the DNA must be complimentary. The double helix forms because of how the molecules fit together due to various circumstances like charge and thermodynamics.So at this point you can think of a picture where a strand of DNA has a sequence where the sequence is dependent on the order of the bases for instance Adenine, Guanine, Adenine, Cytosine, Cytosine, ... or AGACC... is a perfectly good sequence. That very same sequence could be double stranded where one strand would be 5'-AGACC-3' and the other strand would be 5'-GGTCT-3' (read five prime GGTCT three prime). The primes denote how the sequence should be read. If you notice the second strand matches up perfectly with the first strand if you put the 3' end under the 5' end.
The sequence of DNA is very important. Every molecule that interacts with DNA can "read" the sequence and determine where to bind and how to alter the DNA. It is because cellular processes and DNA physics are sequence dependent that we scientists say DNA is the genetic code of an organism. Those bases determine what proteins are made, when to make them, when to make copies, what binds, where it binds, how long it binds, and so much more. In my research, DNA sequence is very important and allows me to make specific sequences based on how DNA interacts with its surroundings. All that will come next time though.

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