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Institut für Physiologie und Pathophysiologie

Mathematical Modelling

Computational Methods are particularly useful in close combination with experimental techniques. This allows the direct input of latest experimental results into the model and vice versa. Therefore, we are developing models for calcium regulation or actin-myosin interaction in parallel to our fluorescence microscopy experiments.

 

Calcium regulation

Calcium ions inside the cell are present in various different "states". In addition to the free ions, calcium is also bound to several intrinsic and extrinsic calcium-binding sites (of which the fluorescence indicator is very often the most important one). Calcium ions can also be sequestered in intracellular membrane-bound organelles, for example, mitochondria, the endoplasmic reticulum (ER), or the sarcoplasmic reticulum (SR) of muscle fibers.

 

All these parameters have to be taken into account for the development of suitable models for the complex process of intracellular calcium regulation. As only calcium ions bound to the fluorescence indicator can be experimentally measured, all other quantities have to be derived from these model calculations.

 

The mathematical treatment requires an intelligent simplification of the associated differential equations using inherent symmetries, like cylindrical symmetry in skeletal muscle. Numerical solutions can finally be obtained with the help of a suitable discrete grid for time and space.

 

 

 

 

Modeling molecular motors

Muscle contraction is based on the interaction of only two proteins: actin and myosin. However, there are a number of associated proteins that are responsible for the regulation and tuning of this molecular motor. We are interested in developing a “motility model” that integrates various factors influencing the speed of shortening and force generation.

 


Neue Publikationen

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Hypertension-evoked RhoA activity in vascular smooth muscle cells requires RGS5. FASEB J. 2017 Dec 5. pii: fj.201700384RR. doi: 10.1096/fj.201700384RR. [Epub ahead of print]

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Modulation of glutathione peroxidase activity by age-dependent carbonylation in glomeruli of diabetic mice. J Diabetes Complications. 2017 Nov 22. pii: S1056-8727(17)31094-2. doi: 10.1016/j.jdiacomp.2017.11.007. [Epub ahead of print]

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Sensitive mass spectrometric assay for determination of 15-deoxy-Δ12,14-prostaglandin J2 and its application in human plasma samples of patients with diabetes. Anal Bioanal Chem. 2017 Nov 16. doi: 10.1007/s00216-017-0748-1. [Epub ahead of print]

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Role of protein carbonylation in diabetes. J Inherit Metab Dis. 2017 Nov 6. doi: 10.1007/s10545-017-0104-9. [Epub ahead of print]

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AP-1 Oligodeoxynucleotides Reduce Aortic Elastolysis in a Murine Model of Marfan Syndrome. Mol Ther Nucleic Acids. 2017 Dec 15; 9: 69–79. Epub 2017 Sep 20. doi: 10.1016/j.omtn.2017.08.014

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Allosteric inhibition of carnosinase (CN1) by inducing a conformational shift. J Enzyme Inhib Med Chem. 2017 Dec;32(1):1102-1110. doi: 10.1080/14756366.2017.1355793.

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Transcription factor decoy technology: a therapeutic update. Biochem Pharmacol. 2017 Nov 15;144:29-34. doi: 10.1016/j.bcp.2017.06.122. Epub 2017 Jun 19. Review.

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Local oxygen homeostasis during various neuronal network activity states in the mouse hippocampus. J Cereb Blood Flow Metab. 2017 Nov 3; 271678X17740091. doi: 10.1177/0271678X17740091

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Subtype-specific differentiation of cardiac pacemaker cell clusters from human induced pluripotent stem cells. Stem Cell Res Ther. 2017 Oct 16;8(1):229. doi: 10.1186/s13287-017-0681-4.

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Heteromeric channels formed by TRPC1, TRPC4 and TRPC5 define hippocampal synaptic transmission and working memory. EMBO J. 2017 Sep 15;36(18):2770-2789. doi: 10.15252/embj.201696369. Epub 2017 Aug 8


Institut für
Physiologie und Pathophysiologie

Universität Heidelberg

Im Neuenheimer Feld 326

69120 Heidelberg

Telefon:+49 6221 54-4056
Telefax:+49 6221 54-6364
E-Mail:susanne.bechtel@
physiologie.uni-heidelberg.de