SP12

Principal Investigator: Stefan H. Heinemann (Dept. of Biophysics, CMB, FSU Jena and Jena University Hospital)

Anogh Muthukumar (PhD): Visualization of protein modifications and their impact on the electrical signalling

Oxidation of methionine residues in proteins gives rise to structural and functional modifications that can accumulate in aged tissue. While massive methionine oxidation results in loss of protein function and degradation, in select cases the protein modification Met(O) persists. We therefore develop and validate molecular fluorescence probes suited to monitor methionine oxidation and the incorporation of selenomethionine in living cells. We are particularly interested in such cases where Met oxidation affects voltage-gated ion channels to exert a gain-of-function effect, i.e., situations in which even a small fraction of modified proteins may cause significant changes in organ function. In NaV channels even minute impairment of inactivation leads to electrical hyperexcitability and an array of pathophysiological phenomena such as cardiac arrhythmia, myotonia, epilepsy, and altered pain sensation. We furthermore investigate how oxidative and nitrosative stress affects the signaling in insulin-secreting INS1 cells.

Marwa Ahmed (PhD): Visualization of protein modifications and their impact on the electrical signalling

Oxidation of methionine residues in proteins gives rise to structural and functional modifications that can accumulate in aged tissue. While massive methionine oxidation results in loss of protein function and degradation, in select cases the protein modification Met(O) persists. We therefore develop and validate molecular fluorescence probes suited to monitor methionine oxidation in living cells and organisms such as yeast and C. elegans. We are particularly interested in such cases where Met oxidation affects voltage-gated ion channels to exert a gain-of-function effect, i.e. situations in which even a small fraction of modified proteins may cause significant changes in organ function. In NaV channels, for example, even minute impairment of inactivation leads to electrical hyperexcitability and an array of pathophysiological phenomena such as cardiac arrhythmia, myotonia, epilepsy, and altered pain sensation. We furthermore investigate potential secondary modification steps, e.g. the formation of protein networks stabilised by sulfilimine bonds.