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Wellcome Trust OXION Training Fellow
Dept. of Biochemistry
University of Oxford
South Parks Road
Telephone: 01865 613304
Fax: 01865 613238
I received my B.A. in Molecular Cellular Developmental Biology (MCDB) and Biochemistry from the University of Colorado-Boulder. My Ph.D training was in Neurobiology from University of California-San Diego and the Salk Institute of Biological Studies. I was a post-doctoral fellow in the MC Biology at University of California-Berkeley before moving to Oxford for the OXION Training Fellowship.
I am interested in understanding the biophysical, pharmacological, and physiological properties of transmembrane proteins. My focus has been on studying the structure-function relationship of ion channels. During my Ph.D training with Dr. Paul A. Slesinger I used electrophysiological tools to identify a physiologically relevant alcohol-binding pocket in KIR3 (GIRK) channels. This work was in collaboration with the Structure Biology lab of Dr.Senyon Choe.
Since then I have been interested in understanding biophysical and structual basis of polymodal sensing in ion channels. Example of polymodal cues are mechanical stretch, temperature, osmolarity, changes in pH and sensitivity to both physiological bio-active lipids. One subclass ion channels that are modulated by these factors are the K2P potassium channels, whose crystal structures have recently been availavable. Unlike the classical tetrameric Potassium channels, K2P channels are dimer of dimers and do not have a typical bundle-cross gate. They serve as a leak potassium channel, and are important in controlling excitability in neurons, muscle and various other eukaryotic cell types. As an OXION training fellow, I am combining computational techniques with experimental tools to gain insight into structure - dynamics - and function of K2P channels. Specifically, I am using MD simulations to 1) understand the basic biophysical pore properties of K2P channels, 2) understand conformational dynamics involved in channel gating and 3) understand channel-lipid interactions. Insights from these simulations are then tested functionally. This work is in collaboration with Prof. Mark S.P. Sansom in the SBCB and Dr. Stephen J Tucker in Biological Physics, as well as the the Integral Membrane Proteins group at the Structural Genomics Consortium in Oxford.
Trick JL, Aryal P, Tucker SJ and Sansom MSP (2015) Molecular simulation studies of hydrophobic gating in nanopores and ion channels.
Biochemical Society Transactions 43(2),146-150 (2015)
Dong YY, Pike ACW, Mackenzie A, McClenaghan C, Aryal P, Dong L, Quigley A, Grieben M, Goubin S, Mukhopadhyay S, Ruda GF, Clausen MV, Cao L, Brennan PE, Burgess-Brown NA, Sansom MSP, Tucker SJ and Carpenter, EP K2P channel gating mechanisms revealed by structures of TREK-2 and a complex with Prozac.
Science 347: 256-1259 (2015) [SCG's link to PDB and PDF]
Aryal P, Abd-Wahab F, Bucci G, Sansom MSP & Tucker SJ. Influence of Lipids on the Hydrophobic Barrier within the Pore of the TWIK-1 K2P Channels.
Channels 9(1): 44-49 (2015) [doi:10.4161/19336950.2014.981987] [PDF]
Aryal P, Sansom MSP and Tucker SJ. Hydrophobic Gating in Ion Channels.
Journal of Molecular Biology 427(1): 121-130 (2014) [doi: 10.1016/j.jmb.2014.07.030 ]
Aryal P, Abd-Wahab F, Bucci G, Sansom MSP & Tucker SJ. A hydrophobic barrier deep within the inner pore of the TWIK-1 K2P potassium channel.
Nature Communications 5:4377 08 July (2014) [doi: 10.1038/ncomms5377] [Movies]
Almeida MC, Hew-Butler T, Soriano RN, Rao S, Wang W, Wang J, Tamayo N, Oliveira DL, Nucci TB, Aryal P, Garami A, Bautista D, Gavva NR, and Romanovsky AA. Pharmacological blockade of the cold receptor TRPM8 attenuates autonomic and behavioral cold defenses and decreases deep body temperature.
Journal of Neuroscience 32: 2086-2099, (2012)
An MC, Lin W, Yang J, Dominguez B, Padgett D, Sugiura Y, Aryal P, Gould TW, Oppenheim RW, Hester ME, Kaspar BK, Ko CP, Lee KF. Achetylcholine negatively regulates development of the neuromuscular junction through distinct cellular mechanisms.
Proc Natl Acad Sci U S A. 107(23):10702-7 (2010)
Aryal P, Dvir H, Choe S, Slesinger PA. A discrete alcohol pocket involved in GIRK channel activation.
Nature Neuroscience 12(8): 988-95. (2009) [doi: 10.1038/nn.2358]
Fowler CE, Aryal P, Suen KF, Slesinger PA. Evidence for association of GABAB receptors with Kir3 channels and regulators of G protein signaling (RGS4) proteins.
Journal of Physiology 580: 51-65 (2007) [doi: 10.1113/jphysiol.2006.123216]
Lin W, Dominguez B, Yang J, Aryal P, Brandon EP, Gage FH Lee K-F. Neurotransmitter achetylcholine negatively regulates neuromuscular synapse formation by a CDK5-dependent mechanism.
Neuron 46(4):569-79 (2005)
Martindale JJ, Wall JA, Martinez-Longoria DM, Aryal P, Rockman HA, Guo Y, Bolli R, Glembotski CC. Overexpression of mitogen-activated protein kinase kinase 6 in the heart improves functional recovery from ischemia in vitro and protects against myocardial infarction in vivo.
Journal of Biological Chemistry. 280(1); 669-76. (2005)
Dance AL, Miller M, Seragaki S, Aryal P, White B, Aschenbrenner L, Hasson T. Regulation of MyosinVI targeting to endocytic compartments
Traffic 5(10): 798:813 (2004)
Lucas DT, Aryal P, Szweda LI, Koch WJ, Leinwand LA. Alterations in mitochondrial function in a mouse model of hypertrophic cardiomyopathy.
American Journal of Physiology (Heart Circ Physiol) 284(2): H575-83. (2003)
|Last updated 24 Feb 2015