| Post: | Reader in Biochemistry |
| Location: | Crpc 5.9 |
| Email: | L.C.Serpell@sussex.ac.uk |
| Telephone numbers | |
| Internal: | 7363 |
| UK: | (01273) 877363 |
| International: | +44 1273 877363 |
Biography
RESEARCH WEBSITE AT
http://www.lifesci.sussex.ac.uk/research/serpell-lab/Serpell_Group/Welcome.html
01.11.06 Reader in Biochemistry University of Sussex
01.11.03 Wellcome career development research fellow, University of Sussex
01.10.00 Wellcome career development research fellow, University of Cambridge, (CIMR)
01.10.97 Independent postdoctoral fellow, Laboratory of molecular biology, MRC centre, Cambridge
01.04.95 Postdoctoral researcher, University of Toronto, Canada
Role
Reader in Biochemistry
Research and teaching
Research
Amyloid fibrils are insoluble, fibrous protein aggregates that accumulate in the tissues in a number of devastating diseases, including Alzheimer's disease, Diabetes type 2 and the Spongiform encephalopathies (eg. BSE, CJD). We have working towards the elucidation of the structure of these fibrillar aggregates using X-ray fibre diffraction and electron microscopy. We have shown that, although amyloid fibrils may be composed of different proteins associated with different diseases, they share common structural features. In particular, we have shown that amyloid fibrils are rich in beta-sheet conformation, irrespective of the conformation of the native precursor protein, and have a cross-beta core structure. Recently, it has become clear that smaller assemblies of amyloidogenic proteins may play a very important role in pathology of the diseases. This has led to our examing amyloid intermediates both structurally and for their cellular effect.
Research funding is awarded from Wellcome trust, BBSRC and Alzheimer's research trust.
Teaching
Course convenor:
- Biological Chemistry (Year 1)
Lectures &/or Practicals:
- Protein Form and Function (Year 3)
- Research Methods in Biochemistry (Year 1)
- Fundamentals of Molecular and Cell biology (Year 1)
- Biological Chemistry (Year 1)
Selected publications
2009
Cross-b spine architecture of fibrils formed by the amyloidogenic segment NFGSVQFV of medin from solid-state NMR and X-ray fibre diffraction measurements. (with Madine J, Copland A and Middleton D) in Biochemistry Journal Volume 48 pp. 3089-3099
Rational design and application of alpha-helical peptide hydrogels. (with Dek Woolfson, Eleanor Banwell and Abelardo, ES) in Nature Materials Volume In press
Self-Assembly of Phenylalanine Oligopeptides: Insights from Experiments and Molecular Dynamics Simulations in Implicit Solvent. (with Karen Marshall, Tamamis,P, Adler-Abramovich, L and Archontis, G) in Biophysical Journal Volume In press
The structural integrity of beta-sheet assembly (invited review). (with Karen Marshall) in Biochemical transactions Volume In press
2008
Amyloid fibrils: abnormal protein assembly. (with Roma Rambaran) in Prion Volume 2 pp. 112-117
Revealing molecular-level surface structure of amyloid fibrils in liquid by means of frequency modulation atomic force microscopy. Nanotechnology 19, 384010-384016 (with Fukuma, T, Mostaert, AS and Jarvis, JP) in Nanotechnology Volume 19 pp. 384010-384016
Structural insights into the polymorphism of amyloid-like fibrils formed by region 20-29 of amylin revealed by solid-state NMR and X-ray fibre diffraction (with Madine, J, Radford, SE and Middleton, D) in Journal of American Chemical Society Volume 130 pp. 14990-15001
2007
A simple algorithm locates beta-strands in the amyloid fibril core of alpha-synuclein, Abeta, and tau using the amino acid sequence alone. (with Sumner Makin, Zibaee, S. and Goedert, M) in Protein Science Volume 16 pp. 906-918
CLEARER: a new tool for the analysis of X-ray fibre diffraction patterns and diffraction simulation from atomic structural models (with Sumner Makin and Sikorski, P.) in Journal of Applied Crystallography Volume 40 pp. 966-972
Engineering nanoscale order into a designed protein fiber (with Andrew Smith, Dek Woolfson, Papapostolou, D., Atkins, E D T. and Oliver, S J.) in Proceedings of the National Academy of Sciences of the United States of America Volume 104 pp. 10853-10858
Sequence Determinants for Amyloid Fibrillogenesis of Human a-Synuclein (with Zibaee, S., Jakes, R. and Fraser, G.) in Journal of Molecular Biology Volume 374 pp. 454-464
Spider Silk and Amyloid Fibrils: A Structural Comparison (with Thusnelda Stromer, Slotta, U., Hess, S. and Spieß, K.) in Macromolecular Bioscience Volume 7 pp. 183-188
Structural analyses of fibrinogen amyloid fibrils (with Benson, M., Liepnieks, J. and Fraser, P.) in Amyloid: The Journal of Protein Folding Disorders Volume 14 pp. 199-203
2006
Diffraction to study protein and peptide assemblies (with Sumner Makin and Sikorski, P.) in Current Opinion in Chemical Biology Volume 10 pp. 417-422
Expression and Characterization of Full-length Human Huntingtin, an Elongated HEAT Repeat Protein. (with Li, W., Carter, W J. and Rubinsztein, D C.) in Journal of Biological Chemistry Volume 281 pp. 15916-15922
Polymerization of human angiotensinogen: insights into its structural mechanism and functional significance (with Stanley, P. and Penelope, E S.) in Biochemistry Journal Volume 400 pp. 169-178
Synuclein Proteins of the Pufferfish Fugu rubripes: Sequences and Functional Characterization (with Yoshida, H., Craxton, M. and Jakes, R.) in Biochemistry Volume 45 pp. 2599-2607
2005
Molecular basis for amyloid fibril formation and stability (with Sumner Makin, Atkins, E, Sikorski, P and Johansson, J) in Proceedings of the National Academy of Sciences of the USA Volume 102 pp. 315-320
Physical Methods for Studies of Fiber Formation and Structure (with Scheibel, T.) in Protein Folding Handbook Weinheim: Wiley-VCH pp. 197-251 ISBN 9783527307845
Structure and morphology of the Alzheimer’s amyloid fibril (Review Article) (with Stromer, T.) in Microscopy Research and Technique Volume 67 pp. 210-217
Structures for amyloid fibrils (mini-review) (with Sumner Makin) in FEBS Journal Volume 272 pp. 5950-5961
X-Ray Diffraction Studies of Amyloid Structure (with Sumner Makin) in Methods in Molecular Biology Volume 299 pp. 67-80
2004
Mutation E46K increases phospholipid binding and assembly into filaments of human a-synuclein . (with Choi, W., Zibaee, S. and Jakes, R.) in FEBS Letters Volume 576 pp. 363-368
Protein Fiber Linear Dichroism for Structure Determination and Kinetics in a Low-Volume, Low-Wavelength Couette Flow Cell (with Dafforn, T R., Rajendra, J. and Halsall, D J.) in Biophysical Journal Volume 86 pp. 404-410
Structural characterisation of islet amyloid polypeptide fibrils (with Sumner Makin) in Journal of Molecular Biology Volume 335 pp. 1279-1288
The Structure of Amyloid (with Sumner Makin) in Fibre Diffraction Review Volume 12 pp. 29-35