Marc Malfois Non-Crystalline Diffraction
Marc Malfois is Beamline Scientist on the Non Crystalline Diffraction Beamline I22. His scientific interests include macromolecules in solution and the change of their state under the influence of different stimuli. The important challenge is to elucidate information (macromolecule shape, supra-molecular assembly/dissociation, dynamic changes, folding/unfolding, fibril formation) when no macromolecule crystals are available.
Email: Marc Malfois
Tel: +44 (0) 1235 778109
Beamline I22: Non-Crystalline Diffraction
Key Research Areas
Solution scattering, biology.
Current Research Interests
One of my research interests is a multi-disciplinary approach to elucidate the structures and mechanisms of protein fibrillation. Protein aggregation is ubiquitous both in nature and in industrial and technological fields (food, pharmaceuticals). There has been a growing interest in understanding the aggregation of proteins into fibrils, due to their similarities with amyloid deposits that are found in the so-called prion diseases. Despite the significance of these processes, there is still a poor understanding of the aggregation pathways and the kinetics of aggregation and no clear outlining of the regimes under which fibrillation occurs. It is crucial in particular to gain insight into the early stages of the process and characterize the pre-fibrillogenesis structures, as it has been suggested that the pathology is caused by the aggregation process rather than the final product. There is a clear shortage of structural data on the precursors of the aggregates, mainly due to the lack of suitable techniques, and this hinders the development of models describing aggregation pathways and predicting aggregate structures from a set of initial conditions.
Another research interest is the determination of protein structures in lipid membranes by small angle scattering (SAXS). Membrane proteins account for 20-30% of the known proteomes, and have pivotal biochemical and pharmacological importance. Despite ongoing advances in the development of crystallographic, solid-state NMR and EM techniques, however, the number of known membrane protein structures remains relatively small (~0.5% of the Protein Data Bank). Recent advances in molecular modelling and instrument design are being exploited in a development programme to determine membrane protein structures at 5 – 10 Å resolution within a membrane environment. The experimental approach is applicable to any protein that can be reconstituted into a lipid vesicle. Ab initio methods can provide information on the overall shape of membrane proteins as well as shape changes.
My final research interest is the determination of low resolution structures of macromolecules in solution. The SAXS technique yields answers to functional questions when high atomic resolution cannot be achieved. Information on low resolution structure, macromolecule mixtures, complex formation and dynamic process of biological molecules under the influence of different stimuli can be provided by solution scattering.
Selected Publications
- "Low-resolution structure of immunoglobulins IgG, IgM and rheumatoid factor IgM-RF from solution X-ray scattering data.", Volkov V.V., Lapuk V.A., Kayushina R.L., Shtykova E.V., Varlamova E.Y., Malfois M., Svergun D.I. J. Appl. Crystallogr., 36, 503-508 Part 3 Sp. Iss. (2003)
- "Insights into signal transduction revealed by the low resolution structure of the FixJ response regulator", Birck C., Malfois M., Svergun D.I., Samama J.P.. J. Mol. Biol., 321 (3), 447-457 (2002)
- "Solution structure of bacteriophage PRD1 vertex complex.", Sokolova A., Malfois M., Caldentey J., Svergun D.I., Koch M.H.J., Bamford D.H., Tuma R. J. Biol. Chem., 276 (49), 46187-46195 (2001)
- "A novel quaternary structure of the dimeric alpha-crystallin domain with chaperone-like activity.", Feil I.K., Malfois M., Hendle J., van der Zandt H., Svergun D.I. J. Biol. Chem., 276 (15), 12024-12029 (2001)
- "Low resolution structure of the sigma 54 transcription factor revealed by x-ray solution scattering.", Svergun D.I., Malfois M., Koch M.H.J., Wigneshweraraj S.R., Buck M. J. Biol. Chem., 275 (6), 4210-4214 (2000)