Biochemistry

Dr. Holger Wille

Holger Wille

Ph.D, Universität Hamburg (Hamburg, Germany)

Associate Professor

Office: 780-248-1712
Lab: 780-248-1711
Fax: 780-492-9352
wille@ualberta.ca

Research:

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.

 

Selected Publications:

The Structure of PrPSc Prions
Wille H, Requena JR.
Pathogens. (2018 Feb 7;7(1). pii: E20. doi: 10.3390/pathogens7010020. Review

Elucidating the structure of an infectious protein.
Zweckstetter, M, Requena, JR, Wille, H.
PLoS Pathogenss (2017) 13 Apr 13(4): e1006229.

The structural architecture of an infectious mammalian prion using electron cryomicroscopy.
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, Wille, H.
PLoS Pathogens (2016) 12, e1005835.

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

Structural studies of truncated forms of the prion protein PrP.
Wan W, Wille H, Stöhr J, Kendall A, Bian W, McDonald M, Tiggelaar S, Watts JC, Prusiner SB, Stubbs G.
Biophysical Journal (2015) 108, 1548-1554.

The structure of human prions: From biology to structural models – Considerations and pitfalls.
Acevedo-Morantes CY, Wille H.
Viruses (2014) 6, 3875-3892.

The structure of the infectious prion protein: Experimental data and molecular models.
Requena JR, Wille H.
Prion (2014) 8, 60-66.

Plasma membrane invaginations containing clusters of full-length PrP(Sc) are an early form of prion-associated neuropathology in vivo.
Godsave SF, Wille H, Pierson J, Prusiner SB, Peters PJ.
Neurobiol Aging (2013) 34: 1621-31.

Degradation of fungal prion HET−s(218-289) induces formation of a generic amyloid fold.
Wan W, Wille H, Stöhr J, Baxa U, Prusiner SB, Stubbs G.
Biophysical Journal (2012) 102:2339-2344.

Evolutionary descent of prion genes from the ZIP family of metal ion transporters.
Schmitt-Ulms G, Ehsani S, Watts JC, Westaway D, Wille H.
PLoS ONE (2009) 4: e7208.

Natural and synthetic prion structure form X-ray fiber diffraction.
Wille H, Bian W, McDonald M, Kendall A, Colby DW, Bloch L, Ollesch J, Borovinskiy AL, Cohen FE, Prusiner SB, and Stubbs G.
Proc Natl Acad Sci U S A (2009a) 106:16990-16995.

Surface charge of polyoxometalates modulates polymerization of the scrapie prion protein.
Wille H, Shanmugam M, Murugesu M, Ollesch J, Stubbs G, Long JR, Safar JG, Prusiner SB.
Proc Natl Acad Sci U S A(2009b) 106:3740-3745.