Oxygen-dependent gene expression is controlled mainly by cytosolic proteins (hypoxia-inducible factors, HIF), which translocate to the nucleus and exert their biological function by modifying gene transcription. Amongst others, HIF stimulate the expression of the erythropoietin gene (EPO) and, thus, red blood cell production. The cytosolic levels of HIF are modulated by oxygen availability as well as by posttranslational modifications of the HIF proteins. Moreover, the relation between oxygen and cytosolic HIF protein levels is also affected by inflammation. The interactions of these parameters are studied in cell culture and other models. The studies are focussed to establish how biological oxygen sensors function and how they can be manipulated on a pharmacological or genetic basis. These approaches are aimed to develop new strategies in treating blood disorders and malignancies.

The molecular regulation of oxygen homeostasis and cellular adaptation is controlled by the transport of proteins through the nuclear membrane. This is specifically true for the transcription factors involved (e.g. hypoxia-inducible factors, HIF) but also for the molecular oxygen sensors (prolyl hydroxylases), which have to be shuttled into the nucleus to exert part of their biological functions. The transport mechanisms that shuttle molecules through the nuclear membrane and their regulation are an important subject with respect to oxygen dependent gene regulation.