California Institute of Technology, Division of Chemistry and Chemical Engineering, Clemons Lab, Pasadena, CA
My time working in the Clemons Lab at Caltech was interesting, enjoyable, and exactly the kind of experience I needed. The Clemons Lab focuses on structural biology, specifically on transmembrane proteins and protein transport/post-translational modification. They mainly use crystallography but work with biochemistry, microbiology, mass spectrometry and electron microscopy.
I began my summer by working on a literature review of the protein FtsW. This protein is part of the peptidoglycan biosynthesis pathway which is present in almost all bacteria. The literature review was essential because it helped me get a good grasp on the protein I was working on, its characteristics, and the pathway it operates in. I also picked up a couple tricks and some software that are really useful when going through large amounts of scientific papers. This review culminated in a presentation to my postdoc liaison where I presented the most up to date knowledge on this protein. This was a great opportunity to get some feedback on how to most effectively present scientific material and practice presenting complex scientific findings in a straightforward, comprehensible manner.
FtsW’s structure has never been determined, which would have made a great project to do in a lab, but due to the restrictions, that was not an option. I decided to focus my efforts on studying the important amino acids in the protein as well as modeling it with different software. This first task required finding large amounts of amino acid sequences of the protein from various organisms, and then performing a Multiple Sequence Alignment (MSA). There are special programs that produce MSAs and once I had the results, I spent some time cleaning them up and interpreting them. I also spent some time modeling proteins with various software like EVCouplings and Robetta. These provided me with many hundreds of models of FtsW. I then had to compare the models against one another and selected for the ‘best’ ones.
FtsW does not work alone, it forms a complex with many other proteins. There are two main proteins that interact with FtsW to form a fully functional complex, Penicillin Binding Protein (PBP) 1b and 3. I wanted to see if it was possible to model all three proteins together in complex, but it was too large. Therefore, I had to spend time looking into the literature to find some clues as to how these proteins interact and I also collaborated with another undergraduate working on a similar project to mine to determine amino acids that have a high likelihood of interacting to form the protein complex.
This was a great experience overall and gave me a good idea of what structural biology and bioinformatics have to offer and the kind of research it entails. Furthermore, it solidified my interest in pursuing a Ph.D. or MD/Ph.D. after college and confirmed I wanted to major in chemistry with a BIMO concentration. I would like to thank Mr. Carlson and the ’68 Center for Career Exploration for giving me the opportunity to spend my summer working at Caltech in the Clemons Lab.