Biomolecular Structure and Biophysics
Mentor / Lab:
Richard J. Kuhn
Specific Research Area / Project:
Flavivirus assembly and structural dynamics
Lab / Personal work-related websites:Kuhn Lab
Our lab studies flaviviruses, which is a group of viruses that includes dengue virus, yellow fever virus, West Nile virus, and Zika virus. Flaviviruses are transmitted by mosquitoes and cause severe disease in humans. During an infection, as the virus exits a cell it undergoes a major structural rearrangement that is part of its maturation. From previous work we know the structure of immature and mature viruses, but the intermediate steps in the process are unclear. For my research I'm using antibodies to trap the virus in an intermediate state and analyzing the structural changes with cryo-electron microscopy (cryo-EM). Cryo-EM is an emerging technique that enables me to take high-resolution images of the virus frozen in a near-native state. In addition, I'm designing fluorescent proteins and developing protein and vesicle purification strategies to study how flaviviruses assemble inside a cell. The main goal of my research is to understand the basic biology behind how flaviviruses assemble and rearrange their structure. A better understanding of viral maturation will also have transitional impact by providing insight into how to design flavivirus vaccines.
I have had a great experience in the PULSe program. One of my favorite aspects of PULSe was the ability to rotate in many different labs across campus, which allowed me to find my research focus as well as make great connections with professors in different departments. I rotated in four labs that covered the departments of Biology, Biochemistry, Chemistry, Biomedical Engineering and Agricultural & Biological Engineering. This freedom was important to me because when I came to Purdue I was interested in structural biology and biophysics, but I wasn’t sure exactly what research field I wanted to work in. My interdisciplinary rotations advanced my breadth of knowledge and now enable me to take an integrative approach in tackling my research problems, in particular combining biology with microscopy and spectroscopy. Another aspect of the PULSe program that I value is the opportunity to learn about entrepreneurship and incorporate entrepreneurial experiences into my research through collaborations with Discovery Park.
- Therkelsen, M.D. and Kuhn, R.J. Structural investigation of alphavirus assembly with capsid-less virus-like particles. Hitchhiker’s Guide to the Biomolecular Galaxy, West Lafayette, IN, May 2016, poster presentation.
- Therkelsen, M.D. and Kuhn, R.J. Developing exosomes as a platform for viral membrane protein expression. Biological Sciences Retreat, Plymouth, IN, November 2015, poster presentation.
- Therkelsen, M.D., Zhang, C., Li, J. and Cheng, J-X. Spectroscopic imaging reveals polarized clustering of lipid droplets in aggressive cancer cells, PULSe Spring Awards Reception, Purdue University, West Lafayette, IN, April 2015, poster presentation.
- Therkelsen, M.D. and Chang, W.J. Molecular characterization of Ichthyophthirius multifiliis, Protist2012, Oslo, Norway, July 2012, oral and poster presentation.
- Therkelsen, M.D., Le Bideau, F. and Thomas C. Synthesis of diphenolamine ligands for ring-opening polymerization initiation, 241st American Chemical Society National Meeting & Exposition, Anaheim, CA, March 2011, poster presentation.
- St John, S.E., Therkelsen, M.D., Nyalapatla, P.R., Osswald, H.L., Ghosh, A.K. and Mesecar, A.D. (2015) X-ray structure and inhibition of the feline infectious peritonitis virus 3C-like protease: Structural implications for drug design. Bioorg. Med. Chem. Lett. 25, 5072-5077.
- Schmidt, A.G., Therkelsen, M.D., Stewart, S., Kepler, T.B., Liao, H.X., Moody, M.A., Haynes, B.F. and Harrison, S.C. (2015) Viral receptor-binding site antibodies with diverse germline origins. Cell 161, 1026-1034.
- MacColl, E., Therkelsen, M.D., Sherpa, T., Ellerbrock H., Johnston, L.A., Jariwala, R.H., Chang W., Gurtowski, J., Schatz, M.C., Mozammal Hossain, M., Cassidy-Hanley, D.M., Clark, T.G. and Chang W.J. (2015) Molecular genetic diversity and characterization of conjugation genes in the fish parasite Ichthyophthirius multifiliis. Mol. Phylogenet. Evol. 86, 1-7.
- Xu, H., Schmidt, A.G., O’Donnell, T., Therkelsen, M.D., Kepler, T.B., Moody, M.A., Haynes, B.F., Liao, H.X., Harrison, S.C. and Shaw, D.E. (2015) Key mutations stabilize antigen-binding conformation during affinity maturation of a broadly neutralizing influenza antibody lineage. Proteins 83, 773-780.
- 2015 Special recognition poster award at PULSe Spring Awards Reception
- 2015 Lynn Fellowship
- Science in Schools Co-Chair 2015-present
- First-Year Mentoring Program, 2015-present