PhD student project 8
(Early Stage Researcher 8, ESR8)
INTERACTION OF AMYLOIDS WITH MEMBRANES
Supervision: Antoinette Killian
Early Stage Researcher: Manikam S Saravanan
Understanding how membranes affect amyloid formation and how amyloid formation affects membrane properties.
ESR 8 will focus on elucidating the molecular nature of the protein/membrane interactions involved in self-assembly of the human islet amyloid polypeptide (hIAPP), which is involved in type II diabetes. By combining complementary approaches, ESR 9 will contribute novel and in-depth insights into hIAPP/lipid interactions that may be relevant for rational design of inhibitors and for understanding general properties of amyloid diseases. Key techniques (e.g. circular dichroism, EM, ThT-fluorescence, cross-linking methods, size exclusion chromatography, monolayer insertion, fluorescence microscopy and spectroscopy, 2H NMR, 31P NMR, preparation of model membrane vesicles with desired properties) are available in-house. NMR (collaboration Boelens), SAXS (collaboration Gros), and more complex biophysical approaches will be performed (collaboration Winter).
Boelens, Gros; Winter (TU Dortmund); UPE
- Khemtémourian L, Doménech E, Doux JP, Koorengevel MC, Killian JA (2011) Low pH acts as inhibitor of membrane damage induced by human islet amyloid polypeptide. J Am Chem Soc 133, 15598-155604.
- Khemtémourian L, Engel MF, Liskamp RM, Höppener JW, Killian JA (2010) The N-terminal fragment of human islet amyloid polypeptide is non-fibrillogenic in the presence of membranes and does not cause leakage of bilayers of physiologically relevant lipid composition. Biochim Biophys Acta 1798, 1805-1811.
- Engel MFM, Khemtémourian L, Kleijer CC, Meeldijk HJ, Jacobs J, Verkleij AJ, De Kruijff B, Killian JA and Höppener JWM (2008) Membrane damage by human islet amyloid polypeptide through fibril growth at the membrane. Proc Natl Acad Sci USA 105, 6033-6038.