Email: sdove @ (at) umass DOT edu
Office: CoRE Building 440
Home Institution: College of Natural Sciences & Commonwealth Honors College, University of Massachusetts- Amherst
Mentor:
Wilma OlsonDeoxyribonucleic acid (DNA) is an essential biological molecule that contains the genetic information for organisms. It can take on various structures. One includes circular DNA. DNA minicircles become essential in gene expression. With that, they're used in gene therapy, vaccine development, and research areas related to pathology and biology. This structure has the ability to supercoil, a natural process involving the structure crossing over itself. This process is also essential in transcription and interactions between it and enzymes. DNA gyrase is an enzyme part of a class called topoisomerases. These enzymes ease transcripton by cutting DNA strands into pieces and rejoining them. DNA gyrase is mainly found in prokaryotes, where it's able to release torsional stress of positively supercoiled DNA and allow RNA polymerase to copy DNA into RNA during transcription. This projects focuses on the effects of binding of DNA gyrase on the topology of DNA.
I spent this week (and before) reading literature provided to me by Dr. Olson and downloading emDNA (a tumultuous process), the software I'll be using throughout this project. I began to understand DNA gyrase's function, as well as protein binding and its effects on DNA structure. The placement of proteins depended largely on mechanical stress, but proteins also have the ability to manipulate it (Clauvelin & Olson). In other papers, they describe supercoiling and its chirality, which can involve torsional stress. This information makes sense and will probably be an essential part of my research. Other than reading, I also met with Dr. Olson. She condensed the readings for me and showed me some of the 3D structures created by emDNA (very interesting). On Thursday, I started working on my presentation and ran tests in the command line. Today (Friday), I started practicing for my presentation and finished the slides.
Clauvelin N, Olson WK, Tobias I. Characterization of the geometry and topology of DNA pictured as a discrete collection of atoms. J Chem Theory Comput. 2012 Mar 13;8(3):1092-1107. doi: 10.1021/ct200657e. PMID: 24791158; PMCID: PMC4004093.
Clauvelin N, Olson WK. Synergy between Protein Positioning and DNA Elasticity: Energy Minimization of Protein-Decorated DNA Minicircles. J Phys Chem B. 2021 Mar 11;125(9):2277-2287. doi: 10.1021/acs.jpcb.0c11612. Epub 2021 Feb 26. PMID: 33635080; PMCID: PMC9434916.
Coleman, Bernard D., et al. “AIP.” AIP Publishing, 15 Apr. 2003, pubs.aip.org/jcp/article/118/15/7127/839730/Theory-of-sequence-dependent-DNA-elasticity.
Vayssières M, Marechal N, Yun L, Lopez Duran B, Murugasamy NK, Fogg JM, Zechiedrich L, Nadal M, Lamour V. Structural basis of DNA crossover capture by Escherichia coli DNA gyrase. Science. 2024 Apr 12;384(6692):227-232. doi: 10.1126/science.adl5899. Epub 2024 Apr 11. PMID: 38603484; PMCID: PMC11108255.
Young RT, Clauvelin N, Olson WK. emDNA - A Tool for Modeling Protein-decorated DNA Loops and Minicircles at the Base-pair Step Level. J Mol Biol. 2022 Jun 15;434(11):167558. doi: 10.1016/j.jmb.2022.167558. Epub 2022 Mar 24. PMID: 35341743; PMCID: PMC9177622.
I spent the beginning of this week revising my slides and presentation notes, after meeting with Dr. Olson to receive feedback on the notes and get photos I needed for the presentation. I gave my presentation on Tuesday and it went okay (I thought it was too quick) and after, I started going through the examples given in the paper discussing emDNA and its utilities (Young et al). During this, I corresponded with Ismaeel Abdulghani, who worked on a captstone project with Dr. Olson. He explained how to use the commands and where to use them (e.g. ./emDNA-topology in the Release folder under emDNA-install). When was looking in the emDNA-install directory, I noticed that I didn't properly copy the repository, which lead to some complications, but I was able to work around this.
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First PresentationI'm grateful to be guided by my mentor Dr. Wilma Olson and Ismaeel Abdulghani, who assisted me in using emDNA. I also would like to thank Lazaros Gallos and Larry Frolov for their support throughout the summer. This project was funded by the NSF through grant CCF-2447342