My Thesis

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My PhD thesis entitled “Functional and Structural Studies of the Human Voltage-Gated Proton Channel” has recently been published online by the Rockefeller University website here. The Thesis covers six years of extensive research that I carried out in the Laboratory of Molecular Neurobiology and Biophysics at the Rockefeller University under the tutelage of Dr Roderick MacKinnon. … Continue reading

The Spark of Life – Book Review

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I had the great pleasure in late October to attend the awarding of the Lewis Thomas Prize for Writing about Science to Dr Frances Ashcroft for her book The Spark of Life. The ceremony included a lecture by the author followed by a dinner at the Rockefeller University President’s  house and further discussion with the … Continue reading

Proton Channels at the Biophysical Society Meeting – 2013

Proton Channel Speakers

This year was a big year for Hv at the Biophysical Society meeting in Philidephia (Feb. 2-6th). With a symposium and a platform session dedicated to Hv related talks, the meeting boasted a large contingent of scientists studying this channel. I was in attendance and really enjoyed meeting all my fellow Hv researchers whose work I have … Continue reading

The importance of charge compensation in the membrane

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In this post I continue my series on the omega current by discussing how a mutation that removes a charged group from the voltage-sensor domain (VSD) would be highly destabilizing and disruptive. The omega current is a leak current that passes through the VSD of mutated voltage-gated cation channels. In some cases, the mutated channels … Continue reading

Journal Club: Tracking a complete voltage-sensor cycle with metal-ion bridges

In this post I would like to start an online discussion about a very interesting recent PNAS paper: Tracking a complete voltage-sensor cycle with metal-ion bridges by Henrion et al. I know that other people in the voltage-gated cation channel field are very interested in this paper and it also relates to many of the … Continue reading

Omega Current Channelopathies

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In this post I will be continuing my series on the omega current. The omega current is a leak current that passes through the voltage-sensor domain (VSD) of mutated voltage-gated cation channels. Mutation of the VSD S4 helix can reveal a cryptic pore that allows ions (H+, Li+, K+, Rb+ and even guanidinium) to cross … Continue reading

The Omega Current

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Mutation of voltage-sensor domains (VSDs) can sometimes lead to ions leaking across the membrane through the VSDs themselves. Ion conduction through the mutated VSD of the Shaker Kv channel was coined the “omega current” by Tombola, Pathak and Isacoff (Tombola et al., 2005). Many different mutations have been identified that result in current leaking through the VSDs of … Continue reading

Pores and Selectivity Filters

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In this post I will be briefly introducing the classical ideas of ion conduction through membrane proteins. The idea of ion channels as selective pores in the cell membrane is very old but is now understood at atomic detail. So what is a channel? What does an ion conductive pore look like? Here, I will … Continue reading

Hv Physiology: Breast Cancer

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In this post I will discuss the role of human Hv1 channels in promoting the pathology and invasiveness of breast cancers. It is well known that cancer consists of normal cells gone awry. As cells age, they can accumulate mutations in their genomes and sometimes these mutations lead to unregulated growth and expansion. The unregulated, … Continue reading

Biochemical Data Constraining the S4 of Hv

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In this post I will finish my series on alignments and homology models. Here, I will discuss three different biochemical studies of the voltage-gated proton channel (Hv) that help to delineate the boundaries of the S4 helix. First, I will discuss the structure of the coiled-coil, which limits where along the primary the sequence of … Continue reading