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Förslaget inkom 2003-04-04

FLUORESCENT AND ELECTROPHYSIOLOGICAL STUDIES OF ION CHANNELS

OBS! ANSÖKNINGSTIDEN FÖR DETTA EXJOBB HAR LÖPT UT.
Nerve signals are electrical signals generated by ion channel proteins in the cell membrane of nerve cells. The ion channels are highly specialized proteins that form voltage-dependent pores that allow the flux of Na+ and K+ ions across the cell membrane.
We are interested in understanding how these voltage-activated ion channel proteins function on a molecular level. Since abnormal function of voltage-activated ion channels have been implicated in human diseases (eg epilepsy and episodic ataxia), an understanding of how they function could lead to the development of treatments for a number of diseases.
During the last decade, voltage-activated ion channels have been extensively studied to try and understand the biophysical mechanism and structure of these channels. A model of voltage-activated channels is emerging from these studies, but many properties of the channels still remain unexplained. For example, the mechanism by which the channels open and close is still unknown. We are studying the functional role of the different channel domains and the regulation of ion channels by ions (Mg2+) and intracellular molecules (kinases). We do this by measuring single ion channel currents (a few picoamperes), detecting single molecules with fluorescence, building models of ion channels using electrostatics and statistical mechanics, and recording the electro-physiological responses in living cells.
An exam project may include the production of a new mutation by site-directed mutagenesis, in vitro production of RNA, injection of RNA into oocytes, electrophysiology recordings in combination with fluorescence measurements to determine the effect of the introduced mutation.
One ongoing project is a fluorescence study of the conformational changes occuring during channel openings. This study uses both electro- physiological and fluorescence methods to understand the molecular movements of the different channel domains during channel opening. This particular PhD project is a collaboration with Professor Rudolf Rigler at Medical Physics at Karolinska Institutet and is financed by Stiftelsen för Strategisk Forskning (NNN).


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