Abstract
IFITMs are interferon-induced membrane proteins that restrict the entry of a broad range of human and animal viruses, including influenza and HIV (1,2). They are also upregulated in certain cancers. Currently, it is unclear how these proteins work. We hypothesise that they change the properties of cellular membranes to prevent the viral membrane fusion events essential for cell entry and infection. The aim of this PhD project is to determine how the physical/chemical properties of cellular membranes (plasma membrane, endosomal membranes) are modified by the expression of IFITM proteins and to understand the mechanisms by which IFITMs restrict virus entry.
References
[1] IFITM proteins – cellular inhibitors of viral entry, S. E. Smith, S. Weston, P. Kellam, M. Marsh, Curr Opin Virol. 4, 71 (2014).
[2] A Membrane Topology Model for Human Interferon Inducible Transmembrane Protein 1, S. Weston S, S. Czieso, I. J. White, S. E. Smith, P. Kellam, M. Marsh, PLoS ONE 9, e104341 (2014).
[3] Virus entry: open sesame, M. Marsh and A. Helenius, Cell 124, 729–740 (2006).
[4] From fixed to FRAP: measuring protein mobility and activity in living cells, E. A. Reits, J. J. Neefjes, Nat Cell Biol. 3, E145–7 (2001); Advanced Fluorescence Microscopy Techniques—FRAP, FLIP, FLAP, FRET and FLIM, H. C. Ishikawa-Ankerhold, R. Ankerhold, G. P. Drummen, Molecules 17, 4047 (2012).
[5] Cell visco-elasticity measured with AFM and optical trapping at sub-micrometer deformations, S. Nawaz et al. PLoS ONE 7, e45297 (2012); Substrate-dependent cell elasticity measured by optical tweezers indentation, M. S. Yousafzai et al., Optics Lasers Eng. 76, 27-33 (2016).