Structural and functional studies of the K-ATP channel and the mechanism of disease-causing mutations
The subject. ATP-sensitive K+ channels (K-ATP) are present in the pancreas, where they control insulin secretion, in the cardiovascular system, where they modulate arterial pressure and response to ischemia, and in the brain, where they are involved in appetite control and neuroprotection. They are a source of diseases when mutated, and a pathway to health as the target for numerous drugs.The K-ATP channel is among the best understood channels in terms of function and physiology and among the least understood in terms of structure. This channel is a unique complex in biology, formed by the assembly of an ABC transporter, SUR, and a potassiumselective pore, Kir6.2. The objectives of the thesis will be to understand how these proteins associate and interact, and how disease-causing mutations (diabetes, cardiopathy,…) modify the communication between the SUR and Kir6.2 subunits. Based on substantial in-progress work, the approach will combine structural (microscopy, crystallography, …) and functional (electrophysiology) studies.
The place. The thesis will take place in the Channels group within the Institute for Structural Biology (http://www.ibs.fr/groups/channels-group). The Channels group focuses on ion channels and membrane protein engineering and is recognized for its work on K-ATP channels and proteic biosensors.
IBS is a renowned institute in the field of structural and molecular biology. It is part of the Grenoble scientific polygon with numerous research institutes and colleges as well as several large instruments such as the European Synchrotron. The site offers a stimulating scientific environment in the natural surroundings of the French Alps.
The candidate. Strong academic credentials. Experience or interest in structural biology or electrophysiology. The granting agency (CEA) will only consider candidates with top-tier academic records. There are no other restrictive conditions and foreigners can, and should, apply. The working language in the lab is English.
The position. The position is for three years starting in October 2012. The salary is very competitive (>2000 €/month).
1) Candidates must apply on-line at “http://www-dsv.cea.fr/en/phd-program/the-internationaldoctoral-
program” before March 11, 2012.
2) Candidates should also send a one-page CV with the names, email & tel of 2 references
to Dr. Michel Vivaudou (email@example.com). Message subject should be “PhD 2012”.
3) Pre-selected candidates will be invited for interviews in Paris in May, all expenses paid.
4) A selection committee will choose the successful candidates in early June 2012.