Sarah Rauscher

PhD candidate
Tel.: (416) 813-6855
email:

Education:

September 2004 - Present: PhD Candidate, Department of Biochemistry, University of Toronto
Toronto, Ontario, Canada
September, 2000 - June, 2004: Honours Bachelor of Science, Major in Physics (Astrophysics Stream), Minor in Chemistry
McMaster University, Hamilton, Ontario, Canada

Past Research / Employment Experience:

• 4th Year Thesis/Summer Research Project 2004 (supervised by Dr. Paul Ayers)
  Development and programming of a novel and efficient algorithm to fold proteins
• NSERC USRA Summer Research Project 2003 (supervised by Dr. Catherine Kallin)
  Theoretical research in high Tc superconductors, focusing on the d-wave vortex state
• NSERC USRA Summer Research Project 2002 (supervised by Dr. Ignacio Vargas-Baca)
  Computational study of the supramolecular chemistry of chalcogen atoms
• NSERC USRA Summer Research Project 2001 (supervised by Dr. Ignacio Vargas-Baca)
  Synthetic inorganic chemistry (synthesis of sulfenamides)
• Teaching Assistant, Department of Physics, McMaster University (2002-2004)

Publications:

1. S. Rauscher, R. Pomès, "Molecular simulations of protein disorder", Biochem. Cell Biol., 88(2):269-90 (2010).
2. A. Nikolic, S. Baud, S. Rauscher, and R. Pomès, "Molecular mechanism of β-sheet self-organization at water-hydrophobic interfaces", Proteins, accepted (2010).
3. S. Rauscher, C. Neale, and R. Pomès, "Simulated Tempering Distributed Replica Sampling, Virtual Replica Exchange, and Other Generalized-Ensemble Methods for Conformational Sampling", J. Chem. Theory Comput., 5(10):2640-2662 (2009).
4. S. Rauscher, S. Baud, M. Miao, F. W. Keeley and R. Pomès (2006) "'Proline and Glycine control protein self-organization into elastomeric or amyloid fibrils", Structure 14, 1667-1676.
5. D. Knapp, C. Kallin, A. Ghosal and S. Mansour (2005) "Antiferromagnetism and charged vortices in high-Tc superconductors", Physical Review B 71, 064504.
6. A. F. Cozzolino, I. Vargas-Baca, S. Mansour and A. H. Mahmoudkhani (2005) "The nature of the supramolecular association of 1,2,5-chalcogenadiazoles", Journal of the American Chemical Society 9, 3184-3190.
7. W. Zhang, A. F. Cozzolino, A. H. Mahmoudkhani, M. Tulumello, S. Mansour and I. Vargas-Baca (2005) "Influence of pi-stacking on the resonant enhancement of the second-order nonlinear optical response of dipolar chromophores", Journal of Physical Chemistry B 109, 18378-18384.
8. A. H. Mahmoudkhani, S. Rauscher, B. Grajales and I. Vargas-Baca (2003) "Structural diversity of lithium sulfenamides: 7Li NMR studies in solution and crystal structures of [Li2(η2-(CH3)3C-NS-C6H4CH3-4)2(THF)2] and [Li2 (η 1-4-CH3C6H4-NS-C6H4CH3-4)2(THF)4]" Inorganic Chemistry 42, 3849-3855.

Current Research Interests:

Elastin provides extensible tissues, including arteries and skin, with the propensity for elastic recoil, whereas amyloid fibrils are associated with tissue-degenerative diseases, such as Alzheimer's. Although both elastin-like and amyloid-like materials result from the self-organization of proteins into fibrils, the molecular basis of their differing physical properties is poorly understood. Using molecular simulations of monomeric and aggregated states, we have shown that elastin-like and amyloid-like peptides are separable on the basis of backbone hydration and peptide-peptide hydrogen bonding. The analysis of diverse sequences, including those of elastin, amyloids, spider silks, wheat gluten, and insect resilin, reveals a threshold in proline and glycine composition above which amyloid formation is impeded and elastomeric properties become apparent. The predictive capacity of this threshold is confirmed by the self-assembly of recombinant peptides into either amyloid or elastin-like fibrils. Our findings support a unified model of protein aggregation in which hydration and conformational disorder are fundamental requirements for elastomeric function.

Conformations of monomers and aggregates of elastin-like and amyloid-like sequences


Significantly-populated structural elements: (A) polyproline II with nearby water; (B) hydrogen-bonded turn; and (C) beta sheet. Backbone representations of monomers and aggregates: (D) & (G) (GVPGV)7; (E) & (H) (GGVGV)7 and (F) & (I) (GVAGGV)6. Chain color indicates residue type: G (yellow), P (red), V (green), A (blue). Proline-containing elastin-like repeats, including GVPGV, form amorphous and disordered aggregates. By contrast, sequences devoid of proline form amyloid-like structures with significant beta sheet content.

Proline and glycine composition of elastomeric and amyloidogenic peptides


A two dimensional plot correlating proline and glycine content for a wide variety of peptides. The coexistence region (shaded in grey) contains P and G compositions consistent with both amyloidogenic and elastomeric properties. Elastomeric proteins, including the domains of elastin, major ampullate spindroin 2 (MaSp2), flagelliform silk, the elastic domains of mussel byssus thread, and abductin, appear above a composition threshold (upper dashed line). Amyloidogenic sequences are primarily found below the PG-threshold, along with rigid lizard egg shells, tubulliform silk (TuSp1), a protective silk for spider eggs, and aciniform silk (AcSp), used for wrapping prey. The coexistence region contains amyloid-like peptides as well as the elastomeric adhesive produced by the frog Notaden bennetti, the PEVK domains of titin, wheat glutenin protein, and the strongest spider silks, namely major ampullate spindroin 1 (MaSp1) and minor ampullate spindroin (MiSp).