Nicholas Fitzkee

Image of Nicholas Fitzkee

Nicholas Fitzkee

Associate Professor

B.S. Carnegie Mellon University, 2001
Ph.D. Johns Hopkins University, 2005

Email

Hand Lab 3310

(662) 325-1288

Website CV

Research Interests

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 two main projects:

Protein interacting with gold nanoparticle, unfolding in one case and remaining folded in the other.Protein-Nanoparticle Interactions

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 1).

An fully disordered protein and a partially folded protein producing the same experimental data.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 2). In this project, we are combining NMR and EPR spectroscopy with molecular modeling to understand the structural properties of these disordered protein systems.

Positions Open

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. 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.

Publications

  1. Woods, K. E., Perera, Y. R., Davidson, M. B., Wilks, C. A., Yadav, D. K., Fitzkee, N. C. (2016) “Understanding Protein Structure Deformation on the Surface of Gold Nanoparticles of Varying Size.” Journal of Physical Chemistry C. (link)
  2. Wang, A. Perera, Y.R., Davidson, M.B., Fitzkee, N.C. (2016) “Electrostatic Interactions and Protein Competition Reveal a Dynamic Surface in Gold Nanoparticle-Protein Adsorption.” Journal of Physical Chemistry C. 120 (42): 24231-24239. (link)
  3. Brown, L.R., Gunnell, S.M., Cassella, A., Keller, L.E., Scherkenbach, L.A. Mann, B., Brown, M.W. Hill, R., Fitzkee, N.C., Rosch, J.W., Tuomanen, E., Thornton, J.A. (2016) “AdcAII of Streptococcus pneumoniae affects pneumococcal invasiveness.” PLOS One. 11 (1): e0146785. (link)
  4. Nettles, W., Song, H., Farquar, E., Fitzkee, N. C., Emerson, J. P. (2015) “Characterization of the Copper(II) Binding Sites in Human Carbonic Anhydrase II.” Inorganic Chemistry. 54 (12): 5671-5680. (link)
  5. Wilder, H., Wozniak, E., Huddleston, E. C., Tata, S., Fitzkee, N. C., and Lopez, J. (2015) “Case Report: A Retrospective Serological Analysis Indicating Human Exposure to Tick-Borne Relapsing Fever Spirochetes in Texas.” PLoS Neglected Tropical Diseases. 9 (4): e0003617. (link)
  6. Siriwardana, K., Wang, A., Gadogbe, M., Collier, W. E., Fitzkee, N. C., Zhang, D. (2015) “Studying the Effects of Cysteine Residues on Protein Interactions with Silver Nanoparticles.” Journal of Physical Chemistry C. 119 (5): 2910-16. (link)
  7. Wang, A., Vo, T., Le, V., Fitzkee, N. C. (2014) “Using Hydrogen-Deuterium Exchange to Monitor Protein Structure in the Presence of Gold Nanoparticles.” Journal of Physical Chemistry B. 118(49): 14148-56. (link)
  8. Wang, A., Vangala, K. Vo, T., Zhang, D., Fitzkee, N. C. (2014) “A Three-Step Model for Protein-Gold Nanoparticle Adsorption.” Journal of Physical Chemistry C. 138: 8134-8142. (link)
  9. Siriwardana K., Wang A., Vangala K., Fitzkee N. C., Zhang D. (2013) “Probing the Effects of Cysteine Residues on Protein Adsorption onto Gold Nanoparticles Using Wild-Type and Mutated GB3 Proteins.” Langmuir. 29: 10990-10996. (link)

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