Dr Nesrine Chakroun
Nesrine has a multidisciplinary background in Biotechnology and Bioinformatics. After graduating, she worked on bacterial Genome Sequencing at the Pasteur Institute Paris, France from 2005. In 2006, she joined the Immune Cell Biology Division at the NIMR, London, before starting her PhD at King’s College London in 2007. Nesrine successfully defended her thesis in July 2011 and, having worked with Dr Franca Fraternali (Randall Division), she recently joined the UCL Department of Biochemical Engineering as a post-doc at the EPSRC Centre for Innovative Manufacturing in Emergent Macromolecular Therapies.
Her project focussed on understanding the early stages of the Prion Protein (PrP) oligomerization leading to the conversion of the alpha-helical rich cellular (PrPc) into a beta-rich structurally modified form (PrPsc). Nesrine used two complementary approaches:
* Small Angle X-ray scattering, for the determination of the oligomeric structures
* Molecular Dynamic (MD) simulations, to study the conversion of the PrP into its pathogenic isoform at the molecular scale.
Fig. 1 MD simulations of a limited region of the PrP, namely, the two helices H2H3 reveals a complete unfolding of H2 and H3 and the formation of a stable beta-rich refolded “double hairpin” structure, a potential nucleus for oligomerization.
- N. Chakroun, A. Fornili, S. Prigent, J. Kleinjung, C. A. Dreiss, H. Rezaei, Franca Fraternali (2013) Decrypting Prion Protein conversion into a β-rich conformer by Molecular Dynamics, J. Chem. Theory Comput., 9, 2455–2465
- Fornili A, Autore F, Chakroun N, Martinez P, Fraternali F. 2012, Protein-water interactions in MD simulations: POPS/POPSCOMP solvent accessibility analysis, solvation forces and hydration sites. Methods Mol. Biol. Vol. 819. 375-392
- Chakroun N, Prigent S, Dreiss CA, Noinville S, Chapuis C, Fraternali F, Rezaei H. 2010, The oligomerization properties of PrP are restricted to a minimal domain. FASEB J Vol. 24. No 9. 3222-3231
- Le Roux F, Zouine M, Chakroun N, Binesse J, Saulnier D, Bouchier C, Zidane N, Ma L, Rusniok C, Lajus A, Buchrieser C, Médigue C, Polz MF, Mazel D 2009, Genome sequence of Vibrio splendidus: an abundant planctonic marine species with a large genotypic diversity. Environmental microbiology. Vol 11, No 8,1959-1970
- Krin E, Derzelle S, Bedard K, Adib-Conquy M, Turlin E, Lenormand P, Hullo MF, Bonne I, Chakroun N, Lacroix C, Danchin A. 2008, Regulatory role of UvrY in adaptation of Photorhabdus luminescens growth inside the insect. Environmental microbiology. Vol 10, No. 5, 1118-1134
- Krin E, Chakroun N, Turlin E, Givaudan A, Gaboriau F, Bonne I, Rousselle JC, Frangeul L, Lacroix C, Hullo MF, Marisa L, Danchin A, Derzelle S. 2006, Pleiotropic Role of Quorum-sensing Autoinducer-2 in Photorhabdus luminescens. Applied and Environmental Microbiology, Vol. 72, No. 10, 6439-6451