My laboratory is particularly interested in posttranscriptional and posttranslational mechanisms of ion channel regulation and their role in the dynamic control of cellular excitability and systems level function in heath and disease.
My laboratory takes an integrative approach to address ion channel function and regulation as well as neuroendocrine control of energy balance and food intake.
Dysregulation of the electrical excitability of cells may lead to major human disorders such as obesity, diabetes and high blood pressure.
Understanding how ion channels are regulated by both environmental (e.g. diet, stress, drugs) as well as genetic (e.g gene mutations) factors is thus crucial to understanding both the causes of such diseases and allow us to define new therapeutic strategies to treat them.
Addressing these issues also underpins one of the major challenges in post-genomic biology: understanding how we generate physiological diversity from a limited genome. My laboratory focuses on the role of the major post-transcriptional (e.g. miRNAs, alternative pre mRNA splicing) and post-translational (e.g. phosphorylation, palmitoylation) drivers for generating proteomic diversity, in controlling ion channel properties and physiology.
We are trying to understand how interaction between these processes and the physiological consequence of changes in these pathways controls defined physiological systems.
Funded largely by the Wellcome Trust, we take a multidisciplinary approach ranging from analysis of splice variant mRNA expression through proteomics of ion channel signalling complexes to analysis of channel function at the systems level using conditional knockout strategies.
As a partner in a new 9M euro study, named Full4health, we are using state of the art neuroscience techniques to examine the role of the brain in the sensing of energy balance and the initiation of food intake.
As well as leading to a greater understanding of signalling between the gut and the brain, it is hoped that the findings will help inform the food industry as to how food could be formulated to help tackle obesity and under-nutrition.
We are funded by the Wellcome Trust and EU FP7.
Liang Z, Chen L, McClafferty H, Lukowski R, Macgregor D, King JT, Rizzi S, Sausbier M, McCobb DP, Knaus HG, Ruth P, Shipston MJ (2011) Control of the hypothalmo-pituitary-adrenal axis activity by the intermediate conductance calcium-activated potassium channel, SK4. J Physiol. 589:5965-86
Jeffries, O., Geiger, N., Rowe, I.C.M., Tian, L., McClafferty, H., Chen, L., Bi, D., Knaus, H.G., Ruth, P., & Shipston, M.J. (2010) Palmitoylation of the S0-S1 linker regulates cell surface expression of voltage- and calcium- activated potassium channels. J Biol Chem 285:33307-33314
Chen, L., Jeffries, O., Rowe, I.C.M., Liang, Z., Knaus, H-G., Ruth, P & Shipston M.J. (2010) Membrane trafficking of large conductance calcium-activated potassium channels is regulated by alternative splicing of a transplantable, acidic trafficking motif in the RCK1-RCK2 linker. J Biol Chem 285:23265-23275.
Tian, L., McClafferty, H., Jeffries, O & Shipston M.J. (2010) Multiple palmitoyltransferases are required for palmitoylation-dependent regulation of large conductance calcium- and voltage- activated potassium channels. J Biol Chem 285: 23954-23962.
Tian, l., Jeffries, O.J., McClafferty, H., Molyvdas, A., Rowe, I.C.M. Saleem, F., Chen L., Greaves, J., Chamberlain, L.H., Knaus, H.G., Ruth P., & Shipston, M.J. (2008) Palmitoylation gates phosphorylation-dependent regulation of BK potassium channels. Proc. Natl. Acad. Sci. USA 105:21006-21011.
McCartney C.E., McClafferty H., Huibant J-M., Rowan E.G., Shipston M.J. & Rowe I.C.M. (2005). A cysteine rich motif confers hypoxia sensitivity to mammalian BK channel ?-subunits. Proc. Natl. Acad. Sci. U.S.A. 102:17870-17876
Tian L., Coghill L. S., McClafferty H., MacDonald S. H-F., Antoni F. A., Ruth P., Knaus H-G. & Shipston M. J. (2004) Distinct stoichiometry of BKCa channel tetramer phosphorylation specifies channel activation and inhibition by cAMP-dependent protein kinase. Proc. Natl. Acad. Sci. U.S.A. 101:11897-11902
Sausbier, M., Hu, H., Arntz, C., Feil, S., Kamm, S., Adelsberger, H., Sausbier, U., Sailer, C. A., Feil, R., Hofmann, F., Korth M., Shipston M .J., Knaus H-G., Wolfer D. P., Pedroarena C. M., Storm J. F. & Ruth P.(2004) Cerebellar ataxia and Purkinje cell dysfunction caused by Ca2+-activated K+ channel deficiency. Proc. Natl. Acad. Sci. U.S.A.101:9474-9478
Duncan, R.R., Grieves, J., Wiegand, U.K., Matskevich, I., Bodammer, G., Apps, D.K., Shipston, M.J. and Chow, R.H. (2003) Functional and spatial segregation of secretory vesicle pools according to vesicle age. Nature 422:176-180 [Front cover]
This article was published on Jan 24, 2012