Brian Chapados (whatido)

A short explanation of what I do for smart people that aren't biologists:

Enzymes are molecular machines that significantly speed up (typically > 1000-fold) chemical reactions. Most enzymes are proteins[1], linear polymers of different subunits folded into a three-dimensional structure. A subset of these enzymes operate directly on DNA, either repairing damage or making a copy of DNA in preparation for cell division. I determine the 3D-structures of enzymes at atomic resolution (1-3 angstroms or 1^-10 nanometers) by growing crystals from purified enzyme samples, and measuring the intensities of X-rays diffracted by the crystals. This process eventually yields an "electron density map", which can be used to determine the position of atoms in the crystal. Since I can see where that atoms are located, I can make predictions about how pieces of the enzyme interact with DNA or other enzymes based on knowledge of chemistry. To test structure-based predictions about the function of enzymes, I change the DNA encoding the enzyme to alter the chemical attributes of the enzyme at a known location. I can then test activity of the mutant enzyme in isolation, or in some cases, introduce the modified enzyme into cells or organisms. Through iterative rounds of analysis, I can determine how an enzyme works.

[1] Not all 'enzymes' are proteins. RNA and DNA can also fold into three-dimensional structures, and catalyze chemical reactions.