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Institute of Physiology and Pathophysiology

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.

 


Recent Publications

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Impact of carbonylation on glutathione peroxidase-1 activity in human hyperglycemic endothelial cells. Redox Biol. 2018 Jun;16:113-122. doi: 10.1016/j.redox.2018.02.018. Epub 2018 Mar 1.

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Improving electrical properties of iPSC-cardiomyocytes by enhancing Cx43 expression. J Mol Cell Cardiol. 2018 May 16. pii: S0022-2828(18)30171-8. doi: 10.1016/j.yjmcc.2018.05.010. [Epub ahead of print]

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Early Blood-Brain Barrier Disruption in Ischemic Stroke Initiates Multifocally Around Capillaries/Venules. Stroke. 2018 May 14. pii: STROKEAHA.118.020927. doi: 10.1161/STROKEAHA.118.020927. [Epub ahead of print]

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In silico assessment of the conduction mechanism of the Ryanodine Receptor 1 reveals previously unknown exit pathways. Sci Rep. 2018 May 2;8(1):6886. doi: 10.1038/s41598-018-25061-z.

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Parallel detection of theta and respiration-coupled oscillations throughout the mouse brain. Sci Rep. 2018 Apr 24;8(1):6432. doi: 10.1038/s41598-018-24629-z.

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Stability and Function of Hippocampal Mossy Fiber Synapses Depend on Bcl11b/Ctip2. Front Mol Neurosci. 2018 Apr 5;11:103. doi: 10.3389/fnmol.2018.00103. eCollection 2018.

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Glycyrrhetinic Acid Antagonizes Pressure-Induced Venous Remodeling in Mice. Front Physiol. 2018 Apr 4;9:320. doi: 10.3389/fphys.2018.00320. eCollection 2018.

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Respiration-Entrained Brain Rhythms Are Global but Often Overlooked. Trends Neurosci. 2018 Apr;41(4):186-197. doi: 10.1016/j.tins.2018.01.007. Epub 2018 Feb 9.

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Hypertension-evoked RhoA activity in vascular smooth muscle cells requires RGS5. FASEB J. 2018 Apr;32(4):2021-2035. doi: 10.1096/fj.201700384RR. Epub 2018 Jan 5.

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VCAM-1 expression is upregulated by CD34+/CD133+-stem cells derived from septic patients. PLoS One. 2018 Mar 30;13(3):e0195064. doi: 10.1371/journal.pone.0195064. eCollection 2018.

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Carnosine Catalyzes the Formation of the Oligo/Polymeric Products of Methylglyoxal. Cell Physiol Biochem. 2018 Apr;46(2):713-726. doi: 10.1159/000488727. Epub 2018 Mar 29.

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Making room for new memories. Science. 2018 Mar 30;359(6383):1461-1462. doi: 10.1126/science.aat1493.

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Bringing European physiologists together. Acta Physiol (Oxf). 2018 Apr;222(4):e13043. doi: 10.1111/apha.13043. Epub 2018 Feb 15.

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Endothelial progenitor cells accelerate endothelial regeneration in an in vitro model of Shigatoxin-2a-induced injury via soluble growth factors. Am J Physiol Renal Physiol. 2018 Mar 7. doi: 10.1152/ajprenal.00633.2017. [Epub ahead of print]

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Astrocytic glutamine synthetase is expressed in the neuronal somatic layers and down-regulated proportionally to neuronal loss in the human epileptic hippocampus. Glia. 2018 May;66(5):920-933. doi: 10.1002/glia.23292. Epub 2018 Jan 19.

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Expansion of functional personalized cells with specific transgene combinations. Nat Commun. 2018 Mar 8;9(1):994. doi: 10.1038/s41467-018-03408-4.


Institute of
Physiology and Pathophysiology

Heidelberg University

Im Neuenheimer Feld 326

69120 Heidelberg

Germany

Phone:+49 6221 54-4035
Fax:+49 6221 54-4038
E-mail:sekretariat.hecker@
physiologie.uni-heidelberg.de