B.S. Carnegie Mellon University, 2001
Ph.D. Johns Hopkins University, 2005
Nearly all of life's essential chemistry is catalyzed by proteins. Each protein is exquisitely tuned for a specific function, from DNA replication to metabolism. Our group uses a combination of physical chemistry, molecular biology, modeling, and NMR spectroscopy to understand the relationship between protein structure and function. Currently, our research is centered around three main projects:
Bacterial biofilms on medical devices and implants are a significant source of hospital related infection, costing lives and hundreds of millions of dollars annualy. The mechanism by which bacteria attach to abiotic surfaces is fundamentally a surface chemistry question, and we are keenly interested in the biophysical forces that drive biofilm formation. To study this, we generate biofilms and develop approaches for reducing or eliminating biofilm formation (Figure 1). On the flip side, we examine the proteins implicated in bacterial attachments and try to characterize the properties that make them good surface binders.
Nanoparticles have been proposed as an effective tool for biosensing and drug delivery. However, in the context of biological fluids, endogenous proteins will spontaneously adsorb to nanoparticle surfaces, complicating the design of useful nanoparticle-based materials. For example, protein misfolding on nanoparticle-based drugs could potentially induce an unwanted immune response. Conversely, if we understood protein structure on nanoparticle surfaces, we could design effective molecular sensors that could couple a nanoparticle's optical properties with protein binding or catalysis. In this project, we employ a multitude of biophysical and analytical approaches to understand how and why protein structure changes upon adsorption (Figure 2).
Structure and Properties of Disordered Proteins
Many eukaryotic proteins are intrinsically disordered and lack no regular tertiary structure. These proteins often have interesting properties, such as the ability to form tight complexes with globular proteins. Other disordered proteins can phase separate from aqueous solution, forming materials with unique chemical properties. However, traditional approaches to understanding globular proteins fail to capture the structural diversity of disordered protein ensembles (Figure 3). In this project, we are combining NMR and EPR spectroscopy with molecular modeling to understand the structural properties of these disordered protein systems.
We are always looking for quality graduate and undergraduate researchers to join our research team. Graduate students interested in joining the lab should have a strong background in mathematics and physical chemistry, as well as an interest in the relationship between protein structure and function. Computer modeling skills are a plus, but these are not required. More important than any past experience, however, is a drive to solve research problems at the cutting edge of biofilm infection and surface fouling. If your heart is in the work, let's talk.
For undergraduates, advanced coursework is not required provided you possess enthusiasm and interest in biophysics research. Freshmen and sophomores have been successful in the group and are encouraged to inquire about open positions.
Asterisks denote undergraduate authors.
- Perera, Y.R.,† Xu, J.X.,† Hughes, A.C.,* Abbood, I.,* Fitzkee, N.C. “Understanding the Adsorption of Peptides and Proteins onto PEGylated Gold Nanoparticles.” Molecules. Submitted (Manuscript ID 1340392). † Contributed equally.
- Perera, Y.R.,† Yadav, R.,† South, T.M.,* McConnell, K.D., Chappell, E.R.,* and Fitzkee, N.C. (2021) “Solution Structure, Dynamics, and Surface Interaction of the Autolysin R2ab Repeat Domain of S. epidermidis.” Journal of Biological Chemistry. Submitted. † Contributed equally.
- Peng, W.; Somarathne, R.P., Don, R.W., Scott, C.N., Fitzkee, N.C., Zhang, D. (2021) “Polarized Resonance Synchronous Spectroscopy as an Informative, Sensitive, and Convenient Technique for Probing Protein Aggregations.” Biomacromolecules. Submitted (bm-2021-00602u).
- Paiz, E.A., Allen, J.H., Correia, J.J., Fitzkee, N.C., Hough, L.E., Whitten S.T. (2021) “Beta Turn Propensity and a Model Polymer Scaling Exponent Identify Disordered Proteins that Phase Separate.” Preprint in bioRxiv (https://doi.org/10.1101/2020.07.06.189613) Journal of Biological Chemistry. Submitted (JBC-D-21-00146). Website available at http://folding.chemistry.msstate.edu/utils/parse.html.
- Xu, J.X., Alom, M.S., Fitzkee, N.C. (2021) “Quantitative Measurement of Multi-Protein Nanoparticle Interactions using NMR Spectroscopy.” Analytical Chemistry. Revisions Requested (ac-2021-019117).
- Xu, J.X., Fitzkee, N.C. (2021) “Solution NMR of Nanoparticles in Serum: Protein Competition Influences Binding Thermodynamics and Kinetics.” Frontiers in Physiology. Accepted. https://doi.org/10.3389/fphys.2021.715419
- Hu, Y., Park, N., Seo, K.S., Park, J., Somarathne, R.P., Olivier, A.K., Fitzkee, N.C., Thornton, J.A. (2021) “Pneumococcal surface adhesion A protein (PsaA) interacts with human Annexin A2 on airway epithelial cells.” Virulence. 12(1): 1841-1854. https://doi.org/10.1080/21505594.2021.1947176
- Somarathne, R.P., Chappell, E.R.,* Perera, Y.R., Yadav, R. Park, J., Fitzkee, N.C. (2021) “Understanding How Staphylococcal Autolysin Domains Interact with Polystyrene Surfaces.” Frontiers in Microbiology. 12: 658373. https://doi.org/10.3389/fmicb.2021.658373
- Tucker, L.J., Grant, C.S., Gautreaux, M.A. Amarasekara, D., Fitzkee, N.C., Janorkar, A.V., Varadarajan, A., Kundu, S., Priddy, L.B.. (2021) “Physicochemical and Antimicrobial Properties of Thermosensitive Chitosan Hydrogel Loaded with Fosfomycin.” Marine Drugs. 19(3): 144. https://doi.org/10.3390/md19030144
- Burcham, L.R., Hill, R.A., Caulkins, R.C., Emerson, J.P. Nanduri, B., Rosch, J.W., Fitzkee, N.C., Thornton, J.A. (2020) Streptococcus pneumoniae Metal Homeostasis Alters Cellular Metabolism. Metallomics. 12(9): 1416-1427. https://doi.org/10.1039/D0MT00118J
- Cai, L., Lim, H., Fitzkee, N.C., Cosovic, B. Jeremic, D. (2020) “Feasibility of Manufacturing Strand-Based Wood Composite Treated with β-Cyclodextrin-Boric Acid for Fungal Decay Resistance.” Polymers. 12 (2): 274. https://doi.org/10.3390/polym12020274
- Perera, Y.R., South, T.M.,* Hughes, A.C.,* Parkhurst, A.N.,* Williams, O.W.,* Davidson, M.B., Wilks, C.A.,*, Mlsna, D.A., Fitzkee, N.C. (2020) “Using NMR to Measure Protein Binding Capacity on Gold Nanoparticles.” Journal of Chemical Education. 97(3): 820-824. https://doi.org/10.1021/acs.jchemed.9b00625
For a complete list of publications, please visit NCBI MyBibliography.