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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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Early alterations in hippocampal perisomatic GABAergic synapses and network oscillations in a mouse model of Alzheimer's disease amyloidosis. PLoS One. 2019 Jan 15;14(1):e0209228. doi: 10.1371/journal.pone.0209228. eCollection 2019.

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Medikamentöse Varikosetherapie aus der Perspektive experimenteller Modelle. Praxis (Bern 1994). 2019 Jan;108(1):31-36. doi: 10.1024/1661-8157/a003147.

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Selective vulnerability of αOFF retinal ganglion cells during onset of autoimmune optic neuritis. Neuroscience. 2018 Nov 21;393:258-272. doi: 10.1016/j.neuroscience.2018.07.040. Epub 2018 Aug 1.

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Genetic ablation of NFAT5/TonEBP in smooth muscle cells impairs flow- and pressure-induced arterial remodeling in mice. FASEB J. 2018 Nov 1:fj201801594R. doi: 10.1096/fj.201801594R. [Epub ahead of print]

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Synaptic entrainment of ectopic action potential generation in hippocampal pyramidal neurons.  J Physiol. 2018 Nov;596(21):5237-5249. doi: 10.1113/JP276720. Epub 2018 Sep 19.

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The Long Noncoding RNA Cancer Susceptibility 9 and RNA Binding Protein Heterogeneous Nuclear Ribonucleoprotein L Form a Complex and Coregulate Genes Linked to AKT Signaling. Hepatology. 2018 Nov;68(5):1817-1832. doi: 10.1002/hep.30102. Epub 2018 Oct 12.

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Reduction of Transplant Vasculopathy by Intraoperative Nucleic Acid-based Therapy in a Mouse Aortic Allograft Model. Thorac Cardiovasc Surg. 2018 Oct 23. doi: 10.1055/s-0038-1673633. [Epub ahead of print]

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The VAMP-associated protein VAPB is required for cardiac and neuronal pacemaker channel function. FASEB J. 2018 Jun 7:fj201800246R. doi: 10.1096/fj.201800246R. [Epub ahead of print]


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