Our research is mainly concerned with the physiology and pathophysiology of the regulation of cellular events. The understanding of signal transduction processes will help to identify potential drug targets.
The major focus of our work is the NO/cGMP-mediated signalling cascade that plays a major role in the cardivascular and neuronal systems.
The NO/cGMP signalling cascade. Neuronal and endothelial NO synthases are regulated by the intracellular calcium concentration, a rise of the calcium concentration leading to activation and NO formation. NO can diffuse into neighbouring cell and stimulate soluble guanylyl cyclase, the enzyme which catalyses the conversion of GTP to cGMP. Cyclic GMP alters the activity of the cGMP receptor molecules (cGMP-dependent protein kinases, cGMP-regulated phosphodiesterases, cGMP-regulated ion channels) finally leading to changes in cellular function.
D. Koesling and A. Friebe (2000): Structure-function relationships in NO-sensitive Guanylyl cyclase. In: Nitric oxide. biology and pathobiology. (ed. L. J. Ignarro) Academic Press, San Diego, San Francisco, New York, Boston, London, Sydney, Tokyo. pp. 369-379