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James Nowick, 15 september 2017, 11am, IECB Emmanuelle Thinon, 28 June 2017, 11 am, IECB Caroline Tokarski, 15 June 2017, 4pm, ENSCBP Christian Salesse, 8 June 2017, 4pm, ENSCBP Patrice Rey, 01 June 2017, 2h30 pm, ENSCBP Christina Sizun, 18 May 2017, 4 pm, ENSCBP Marisela Velez, 5 May 2017, 11am, IECB Iqbal Choudhary, 27 April 2017, 4 pm, ENSCBP Vincent Aucagne, 21 April 2017, 11 am, IECB Sophie Zinn-Justin, 14 April 2017, 11 am, IECB Cécile Feuillie, 16 February 2017, 4 PM, ENSCBP Félix M. Goñi, 8 december 2016, 4 pm, ENSCBP Félix M. Goñi, 17 november 2016, 4 pm, ENSCBP Carl Creutz, 20 october 2016, 4 pm, ENSCBP Diego Romero, 30 september 2016, 11 am, IECB A. Ciaccafava, 8 september 2016, 14h, ENSCBP A. Ramamoorthy, 16 June 2016, 16h, ENSCBP Alexandre de Brevern, 2 june 2016, ENSCBP Isabelle Landrieu, 26 May, 16h, ENSCBP Frances Sepavoric, 12 May, 16h, ENSCBP Thomas Pradeu, 7 April 2016, 9h, ENSCBP Françoise Argoul, 3 march 2016, 16h, ENSCBP Corinne Loutelier-Bourhis, 16/12/2015, 16h Aristotelis XENAKIS, 3 december 2015, 16h Fabian Kiessling, 26 november 2015, 11h Michaël Molinari, 20 november 2015, 11h Dipankar Das Sarma, 28 October 2015, 14h. Olivier Donard, 22 october 2015, 16h, ENSCBP E. Morvan & A.Grelard, 17/12/2015, 16h, ENSCBP Christophe Cullin, 10 september 2015, 14 h Brigitte Lindet, 18 June 2015, 16h, ENSCBP(B) Marion Decossas, 4 June 2015, 16h, ENSCBP(B) Pascale Schellenberger, 21 Mai 2015, 16h F. Leal-Calderon, 7 May 2015, 16h, ENSCBP(B) Ibrahim Abdulhalim, 9 April 2015, 14h, ENSCBP Manon Carré, 26 March 2015, 14h, ENSCBP(B) C. Bure & JM Schmitter, 19 March 2015, 16h T. Ogata & H. Ihara, 17 March 2015, 11h, IECB Banafshe Larijani, 12 March 2015, 16h, ENSCBP
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James Nowick, 15 september 2017, 11... Emmanuelle Thinon, 28 June 2017, 11... Caroline Tokarski, 15 June 2017, 4p... Christian Salesse, 8 June 2017, 4pm... Patrice Rey, 01 June 2017, 2h30 pm,... Christina Sizun, 18 May 2017, 4 pm,... Marisela Velez, 5 May 2017, 11am, I... Iqbal Choudhary, 27 April 2017, 4 p... Vincent Aucagne, 21 April 2017, 11 ... Sophie Zinn-Justin, 14 April 2017, ... Cécile Feuillie, 16 February 2017,... Félix M. Goñi, 8 december 2016, 4... Félix M. Goñi, 17 november 2016, ... Carl Creutz, 20 october 2016, 4 pm,... Diego Romero, 30 september 2016, 11... A. Ciaccafava, 8 september 2016, 14... A. Ramamoorthy, 16 June 2016, 16h,... Alexandre de Brevern, 2 june 2016, ... Isabelle Landrieu, 26 May, 16h, ENS... Frances Sepavoric, 12 May, 16h, ENS... Thomas Pradeu, 7 April 2016, 9h, EN... Françoise Argoul, 3 march 2016, 1... Corinne Loutelier-Bourhis, 16/12/20... Aristotelis XENAKIS, 3 december 201... Fabian Kiessling, 26 november 2015,... Michaël Molinari, 20 november 2015... Dipankar Das Sarma, 28 October 2015... Olivier Donard, 22 october 2015, 16... E. Morvan & A.Grelard, 17/12/2015, ... Christophe Cullin, 10 september 201... Brigitte Lindet, 18 June 2015, 16h,... Marion Decossas, 4 June 2015, 16h, ... Pascale Schellenberger, 21 Mai 2015... F. Leal-Calderon, 7 May 2015, 16h, ... Ibrahim Abdulhalim, 9 April 2015, 1... Manon Carré, 26 March 2015, 14h, ... C. Bure & JM Schmitter, 19 March 20... T. Ogata & H. Ihara, 17 March 2015,... Banafshe Larijani, 12 March 2015, 1...
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James Nowick, 15 september 2017, 11am, IECB

The seminar will take place, the 15th of september 2017, at 11 am, in the IECB amphitheatre, 2 rue Robert Escarpit Pessac.

 

Unlocking the Mysteries of Amyloid Diseases with Macrocyclic β-Sheet Peptides

 

Dr. James S. Nowick

Professor of Chemistry & Department Chair

University of California

Irvine, CA 92697-2025, USA

jsnowick@uci.edu

https://www.chem.uci.edu/~jsnowick/groupweb/

 

Abstract

 

Amyloid oligomers have emerged as the key toxic species in amyloid diseases. Our laboratory is determining the structures and mechanism of action of oligomers of peptides and proteins associated with Alzheimer's disease, Parkinson's disease, frontotemporal dementias, type II diabetes, and other diseases involving protein aggregation. We are able to obtain high-resolution structures by constraining fragments of the peptides and proteins to β-hairpins and determining the structures of the oligomers that form by X-ray crystallography. Through these studies, in conjunction with biophysical and cell biology experiments, we are gaining new insights into the molecular basis of amyloid diseases.

 

 

Alzheimer's disease has been a major focus of our efforts. The 40-42 amino acid peptide Aβ aggregates to form fibrils and toxic oligomers. While the fibrils and the resulting plaques are the visible hallmark of the disease, the soluble oligomers are now thought to be the damaging species responsible for neurodegeneration. By constraining peptides derived from Aβ to a β-hairpin conformation and preventing fibril formation by N-methylation, we have discovered that triangular trimers constitute a fundamental building block of amyloid oligomers. Through X-ray crystallography, we have elucidated high-resolution structures of the trimers, as well as the hexamers, dodecamers, and annular pores that the trimers form. We are now beginning to correlate the biophysical and biological properties these oligomers with those formed by full-length Aβ. This talk will describe our ongoing studies.

 

 

 

X-ray crystallographic structures of a trimer, dodecamer, and annular pore formed by an Aβ17–36 β-hairpin.(JACS 2016, 138, 4864. PDB 5HOX)

 

Selected Bibliography

 

1. "X-ray Crystallographic Structures of Trimers and Higher-Order Oligomeric Assemblies of a Peptide Derived from Aβ17–36" Spencer, R.; Li, H.; Nowick, J. S. J. Am. Chem. Soc. 2014, 136, 5595-5598.

2. "X-ray Crystallographic Structures of Oligomers of Peptides Derived from β2-Microglobulin" Spencer, R. K.; Kreutzer, A. G.; Salveson, P. J.; Li, H.; Nowick, J. S. J. Am. Chem. Soc. 2015, 137, 6304–6311.

3. "X-ray Crystallographic Structure of Oligomers Formed by a Toxic β-Hairpin Derived from α-Synuclein:Trimers and Higher-Order Oligomers" Salveson, P. J.; Spencer, R. K.; Nowick, J. S. J. Am. Chem. Soc. 2016, 138, 4458−4467.

4. "X-ray Crystallographic Structures of a Trimer, Dodecamer, and Annular Pore Formed by an Aβ17–36 β-Hairpin" Kreutzer, A. G.; Hamza, I. L.; Spencer, R. K.; Nowick, J. S. J. Am. Chem. Soc. 2016, 138,4634−4642.

5. "Stabilization, Assembly, and Toxicity of Trimers Derived from Aβ" Kreutzer, A. G.; Yoo, S.; Spencer, R.K.; Nowick, J. S. J. Am. Chem. Soc. 2017, 139, 966–975.

 

Short biography

 

James Nowick is a Professor of Chemistry at the University of California, Irvine. He received his Bachelors degree in Chemistry in 1985 from Columbia University and his Ph.D. degree in Organic Chemistry in 1990 from MIT, where he was both an NSF Graduate Fellow and an ACS Division of Organic Chemistry Graduate Fellow. After an NSF postdoctoral fellowship in supramolecular chemistry at MIT, he began his independent career as an Assistant Professor at UCI in 1991. He was promoted to Associate Professor in 1996 and Professor in 1998. He is currently Chair of the Department of Chemistry.

 

Contact: Gilles Guichard, g.guichard@iecb.u-bordeaux.fr

 

 

 

 

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