Pictured above: Me and my friends; Working on blog together; Gel electrophoresis
Through my time at the Fred Hutch Pathways Explorers Program, I had the honor and privilege of taking part in many varying tours, labs, talks, and discussions. These all cultivated into a unique and amazing experience. However, a highlight of the program was the Stoddard lecture and the accompanying tour. Dr. Stoddard's expertise is protein structure and engineering. One of the lessons I got out of the Stoddard lecture was: the 3-dimensional structure of a protein is extremely important and interesting. The ability to see the full structure of the protein allows us to gain a holistic understanding of the proteins function, which aids in the creation of medicines and drugs.
For a while, the most common way to see protein structure -and the way 86% of the protein database entries were figured out- was X-ray crystallography. For context, proteins are chains of amino acids that fold into 3-dimensional structure, the structure of a protein determines its function. Proteins have many functions including transporting molecules throughout the body and playing crucial roles in the immune system. The number of protein structures discovered has grown exponentially over the last 50 years, most of these discoveries are due to X-ray crystallography. The process of X-ray crystallography begins with creating lots and lots of proteins in an aqueous solution, which are then purified (unnecessary molecules are removed). Then the proteins are crystalized, this process is the most tedious and can take the most time. Vapor diffusion is a common method to crystalize proteins: small drops of protein solution are placed near a liquid with more concentrated chemicals, and over time, the drop and the concentrated chemicals balance out, causing crystals to form in the drop. The crystals then are put in a big machine and a beam of X-rays is directed at the beam; the crystal structure of the protein causes the X-rays to reflect in different directions. By measuring the direction and intensity of the reflected X-rays, a computer can create a model of the arrangement of atoms in the protein crystal. The final product is the protein's structure, finally solved.
A simplified workflow for solving a protein’s structure
This lecture that Dr. Stoddard gave stuck with me. Having taken AP Biology this past year, I had already delved deeper into Biology than a general course would have allowed. I found organelles and biomolecules fascinating but had no idea how this fascination could be translated into something of practical use. However, this lecture opened a door that was previously locked, bolted, and boarded. Structural biology stuck out to me not only because of its connection to the building of knowledge, but also because this knowledge could significantly help people. Gleevec is an oral medication, and the first targeted cancer treatment. Gleevec attaches to tyrosine kinase -a protein involved in cell division and growth- in cancerous blood cells. When Gleevec binds to tyrosine kinase, tyrosine kinase stops sending growth signals, causing the cancerous blood cell to die. Gleevec binds precisely to the tyrosine kinase protein, which is only possible due to knowing the structure of the protein Gleevec and tyrosine kinase. Thank you so much to Dr. G, Dr. Stoddard and all my fellow session 2 explorers for making this experience so rewarding and enjoyable.
Imatinib’s – sold under the name “Gleevec”- protein structure
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