Working group Pohl: Membrane Biophysics

WG Pohl focuses on the regulation and functions of membrane proteins, in particular mitochondrial proteins. Membrane proteins are currently prime drug targets for more than half of all pharmaceuticals. An understanding of their function and regulation mechanisms will thus provide a valuable contribution to the discovery and further improvement of drugs. At least three aspects of this research area have a significant impact to veterinary and human medicine.

 

a

Polyunsaturated fatty acids (PUFA) constitute an important group of molecules that promote mammals’ health in many aspects. n-6 PUFA were reported to stabilize heart function at low body temperature during hibernation, whereas long chain n-3 PUFA may boost oxidative capacity. Mammals lack the ability to synthesize several PUFA. The incorporation of PUFA into membrane phospholipids is believed to depend directly on dietary influx, or, PUFA can be selectively supplied from internal body depots during hibernation (e.g. for marmots). In both cases, PUFA substantially contribute to the modification of membranes thereby altering membrane protein function (calcium carrier SERCA, uncoupling protein 1 (UCP1)). This has important medical implications for determining disease origin and could aid in preventing cardiovascular diseases, diabetes, atherosclerosis, osteoarthritis, and other chronic disease processes.

Additional aspects of interest arise for the regulation of small animal’s body temperature during anesthesia.

 

b

Several mitochondrial proteins, among them uncoupling proteins 2-5 (UCPs) are thought to be involved in the pathogenesis of cancer, metabolic disorders, neurodegeneration and ischemia by regulating the amount of free radicals. The study of transport characteristics, regulation, distribution and function of mitochondrial proteins would therefore contribute to the understanding of diseases of origin and molecular mechanisms.

 

c

Recently, our group and other research groups described the up-regulation of UCP2 in highly proliferative stem cells. The application of stem cells is important for the treatment of different diseases, in particular, orthopedic injuries and joint diseases in horses and dogs in veterinary medicine. Part of our present projects concentrats on the UCP involvement in signaling pathways relevant to regulation of cell proliferation and differentiation.

To study the different aspects of mitochondrial proteins, a wide range of state-of-the-art methods were established in the last two years. The most important ones are:

(a) electrophysiological measurements of protein conductance in planar lipid bilayers

(b) production and purification of mitochondrial recombinant proteins

(c) two-photon microscopy, fluorescence correlation spectroscopy and fluorescence life-time imaging.

By implementing these methods, the measurements of protein transport characteristics, membrane potential, ion concentrations and protein-ligand interactions are possible.

These research foci are a part of the university´s profile line 1.

 
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