Research

The members of the department perform basic research but the investigations are also related to disease. Different areas are the focus of the research:

(1) 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.

(2) 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.

(3) Organ perfusion is regulated by diameter changes of the smallest arteries (arterioles). The arteriolar diameters are controlled by endothelial cells, which form the innermost cell layer in vessels. The endothelium modulates the activity of the adjacent smooth muscle cell by releasing different dilator and constrictor mediators and thereby exerts its control function on vascular tone and thus blood flow. Endothelial function is studied by means of intravital microscopy in the skeletal muscle of mice, using the isolated perfused heart or isolated vessels but also by telemetric measurement of arterial pressure in conscious animals. The arterioles that provide and control blood flow to the tissues can be directly observed using intravital microscopy. Thus, vascular diameter, blood flow velocity, and the membrane potential of vascular cells (endothelial and smooth muscle cells) can be directly assessed. A topic of special interest is the coordination of vascular cell behaviour along the length of the vessel as vascular cells do not act independently of each other but form a coordinated cellular network. Many vasomotor stimuli do not only elicit a diameter change at the site of localized application but also induce diameter changes at remote upstream sites without stimulating these areas directly. Such remote vascular responses (conducted response) require intercellular connections allowing signals to be transmitted from cell to cell. The molecular bricks of these channels are the connexin proteins which cluster to form so-called gap junctions. Overall, the studies are aimed to examine the role of endothelial mediators and gap junction proteins (connexins) in the control of blood flow to the tissues.

(4) In collaboration with the Department for Integrative and Experimental Genomics, genes that have been demonstrated to be associated with myocardial infarction and coronary disease are examined to identify their functional roles in physiologic and pathophysiologic models. Hitherto, blood pressure measurement, development of atherosclerosis, and thrombus formation are studied in vivo in gene-deficient mice. The studies are aimed to identify how certain genes lead to coronary diseases and provide new ideas for treatment strategies.

(5) Isolated perfused kidneys of mice and rats are used as a model to study renal effects of hormones and drugs.

Courses

Physiology explains how the body works, starting from the molecule up to the integration of organ function into the overall organism. Profound knowledge about physiology is of special importance for medical students. They are taught during the 3rd and 4th semester in lectures, seminars and practical courses in physiology. Different specialized courses (heart and circulatory physiology, exercise physiology) can be chosen by interested students to gain further insight.

Physiology is also important for students in other programs. Molecular Life Science (MLS), Psychology, as well as Mathematics and Medicine in Life Sciences (MML) programs require basic knowledge of physiology which is delivered in lectures and practical courses adapted to the needs of the program. Even in technical student programs of the university (Medical Engineering and Medical Computer Science) and of the university of applied sciences (Audiology and Biomedical Engineering) specificied knowledge about physiology is important and delivered by the members of the department.