Our lab is working to understand a tiny molecular machine found in all human cells. This machine, called the spliceosome, plays a critical role in how our genes encode for an organism as unique and complex as a human being. We know that genes represent packets of information that together serve as a blueprint for an individual. However, in order for these genetic instructions to be used to create our tissues and bodies, our genes must first be read and edited before finally being translated into the building blocks of our cells. As a result of the human genome project, we have come to realize that the editing process, termed splicing, explains how humans can have only five times as many genes as simple single-celled organisms and yet develop into an extremely complex organism with a brain that has billions of precise neural connections.
As the molecular machine that performs splicing, the spliceosome is itself quite complicated. It is made up of over 100 individual parts (each encoded by their own gene!). These parts, proteins and RNAs, come together on a gene transcript to cut out regions of the transcript and paste the remaining pieces back together. Although we know what the spliceosome does, we do not have a very good understanding of how all the parts work together to do splicing. Because it is often very helpful to see a machine in order to understand how it works, our research group uses the tools of structural biology to figure out what the spliceosome looks like doing its job. We use electron microscopes and a technique called X-ray crystallography to build 3D models of the entire spliceosome and its individual parts. These models represent an important part of the basic knowledge that we and other scientists need in order to understand how our genetic information is processed. And because many diseases, including cancers, can arise when changes in that information lead to creation of abnormal cells or conditions, this information will be the foundation on which new medical breakthroughs in detecting and treating these diseases will rest.