Holger Wille

 Associate Professor
PhD, Universität Hamburg (Hamburg, Germany)

Department of Biochemistry
Centre for Prions and Protein Folding Diseases
Faculty of Medicine & Dentistry
University of Alberta
110C Brain and Aging Research Building
Edmonton, Alberta, Canada  T6G 2M8
Tel:  780.248.1712
Lab Tel:  780.248.1711
Fax: 780.492.9352
The general focus of my work is the structure of amyloids and other disease-related, misfolded proteins. In particular, I am interested in the infectious prion protein (PrPSc) and the structure-function relationship underlying its infectious nature. In recent years, mounting evidence has implicated prion-like mechanisms in other neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Lou Gehrig’s disease. The mechanistic similarities and their molecular underpinnings represent interesting research avenues beyond the classical prion diseases. The scope of my current experimental approaches is centered on electron microscopy, three-dimensional reconstruction approaches, X-ray fiber diffraction, and other biochemical and biophysical methods. 
Lab Members:
Claudia Acevedo-Morantes, Graduate Student
Sara Amidian, Graduate Student
Andrew Fang, Graduate Student
Jose Miguel Flores Fernandez​, Postdoctoral Fellow
Razieh Kamali Jamil, Graduate Student
Vineet Rathod, Graduate Student
Brian Tancowny, Research Technologist
Xinli Tang, Research Associate
Xiongyao Wang, Electron Microscopist 
Selected Publications:

Zweckstetter, M, Requena, JR, and Wille, H (2017). Elucidating the structure of an infectious protein. PLoS Pathogens, 13, e1006229

Vázquez-Fernández, E, Vos, MR, Afanasyev, P, Cebey, L, Sevillano, AM, Vidal, E, Rosa, I, Renault, L, Ramos, A, Peters, PJ, Fernández, JJ, van Heel, M, Young, HS, Requena, JR, and Wille, H (2016). The structural architecture of an infectious mammalian prion using electron cryomicroscopy. PLoS Pathogens, 12, e1005835.    

Fang, C, Imberdis, T, Garza, MC, Wille, H, and Harris, DA (2016). A neuronal culture system to detect prion synaptotoxicity. PLoS Pathogens, 12, e1005623.    

Wan, W, Wille, H, Stöhr, J, Kendall, A, Bian, W, McDonald, M, Tiggelaar, S, Watts, JC, Prusiner, SB, and Stubbs, G (2015). Structural studies of truncated forms of the prion protein PrP. Biophysical Journal, 108, 1548-1554. 
Acevedo-Morantes, CY, Wille H (2014). The structure of human prions: From biology to structural models – Considerations and pitfalls. Viruses, 6, 3875-3892.
Requena, JR, Wille, H (2014). The structure of the infectious prion protein: Experimental data and molecular models. Prion 8, 60-66.
Godsave SF, Wille H, Pierson J, Prusiner SB, Peters PJ. (2013) Plasma membrane invaginations containing clusters of full-length PrP(Sc) are an early form of prion-associated neuropathology in vivoNeurobiol Aging. 34:1621-31.
Wan W, Wille H, Stöhr J, Baxa U, Prusiner SB, and Stubbs G (2012). Degradation of fungal prion HET−s(218-289) induces formation of a generic amyloid fold. Biophysical Journal 102:2339-2344.
Schmitt-Ulms G, Ehsani S, Watts JC, Westaway D, and Wille H. (2009). Evolutionary descent of prion genes from the ZIP family of metal ion transporters. PLoS ONE 4:e7208.
Wille H, Bian W, McDonald M, Kendall A, Colby DW, Bloch L, Ollesch J, Borovinskiy AL, Cohen FE, Prusiner SB, and Stubbs G (2009a). Natural and synthetic prion structure form X-ray fiber diffraction. Proceedings of the National Academy of Sciences U.S.A  106:16990-16995.
Wille H, Shanmugam M, Murugesu M, Ollesch J, Stubbs G, Long JR, Safar JG, and Prusiner SB (2009b). Surface charge of polyoxometalates modulates polymerization of the scrapie prion protein. Proceedings of the National Academy of Sciences U.S.A. 106:3740-3745.