Probing the Mechanism of Gating in Sodium Channels by Experiment and Computation


Voltage-gated Na+-channels are transmembrane proteins that are responsible for the fast depolarizing phase of the action potential in nerve and muscular cells. In humans, mutations in these channels cause a wide rang of cardiovascular and neurological diseases. This project will entail both experimental techniques (molecular biology, biochemistry, crystallography) and computational methods (Molecular dynamics simulations and bioinformatics) to investigate the structure/function relationships, especially the permeation and gating processes, for voltage-gated sodium channels. 


B Mifsud, F Tavares-Cadete, AN Young, R Sugar, S Schoenfelder, L Ferreira, SW Wingett, S Andrews, W Grey, PA Ewels, B Herman, S Happe, A Higgs, E LeProust, GA Follows, P Fraser, NM Luscombe and CS Osborne. Mapping long-range promoter contacts in human cells with high-resolution capture Hi-C. Nature Genetics. DOI: 10.1038/ng.3286.


S Schoenfelder, M Furlan-Magaril, B Mifsud, F Tavares-Cadete, R Sugar, BM Javierre, T Nagano, Y Katsman, M Sakthidevi, SW Wingett, E Dimitrova, A Dimond, LB Edelman, S Elderkin, K Tabbada, E Darbo, S Andrews, B Herman, A Higgs, E LeProust, CS Osborne, JA Mitchell, NM Luscombe and P Fraser. The pluripotent regulatory circuitry connecting promoters to their long-range interacting elements. Genome Res. 25(4): 582-97.


Prickett, A.R., Barkas, N., McCole, R.B., Hughes, S., Amante, S.M., Schulz, R., and Oakey, R.J. Genomewide and parental allele specific analysis of CTCF and Cohesin binding sites in mouse brain reveals a tissue-specific binding pattern and an association with differentially methylated regions. Genome Res 2013. 23(10):1624-1635. PMID: 23804403

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Genes, development and STEM approaches to biology