Systems Biology Modeling of the Brain in Health & Disease
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www.drbrowncares.com Introducing the Spinocerebellar Ataxia Modeling Suite, which integrates a variety of molecules, proteins, ion channels, and ions, along with their associated reaction-diffusion and signaling pathways. This modeling suite is a prime example of using computational biology for translational, precision, and systems medicine. Health and disease are both simulated in these publicly available models. References are provided for each paper that describes model development and results. @drbrowncares
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Systems Biology Modeling of the Brain in Health & Disease
- 1. Systems Biology Modeling ofSystems Biology Modeling of the Brain in Virtual Cellthe Brain in Virtual Cell Sherry-Ann Brown, MD, PhD @drbrowncares, drbrowncares@gmail.com
- 2. Modeling in Virtual CellModeling in Virtual Cell @drbrowncares drbrowncares@gmail.com Brown & Loew, Frontiers in Neuroscience 2015-1
- 3. Modeling in Virtual CellModeling in Virtual Cell @drbrowncares drbrowncares@gmail.com Brown & Loew, Frontiers in Neuroscience 2015-1
- 4. Modeling in Virtual CellModeling in Virtual Cell @drbrowncares drbrowncares@gmail.com Brown & Loew, Frontiers in Neuroscience 2015-1
- 5. Hernjak et al, Biophysical Journal 2005 Parallel fiber stimulus Climbing fiber stimulus @drbrowncares drbrowncares@gmail.com Calcium Pathways In The Cell
- 6. Modeling in Virtual Cell @drbrowncares drbrowncares@gmail.com Max 8120 1400 Min Brown et al, Biophysical Journal 2008
- 7. Modeling in Virtual CellModeling in Virtual Cell Max 8120 1400 Min @drbrowncares drbrowncares@gmail.com Brown et al, Biophysical Journal 2008
- 8. @drbrowncares drbrowncares@gmail.com Brown et al, Frontiers in Neuroscience 2015-2
- 9. @drbrowncares drbrowncares@gmail.com Brown et al, Frontiers in Neuroscience 2015-2
- 10. @drbrowncares drbrowncares@gmail.com Brown et al, Frontiers in Neuroscience 2015-2
- 11. Modeling in Virtual CellModeling in Virtual Cell @drbrowncares drbrowncares@gmail.com Brown & Loew, Frontiers in Neuroscience 2015-1
- 12. Modeling in Virtual CellModeling in Virtual Cell @drbrowncares drbrowncares@gmail.com Brown et al, Frontiers in Neuroscience 2015-2
- 13. Modeling in Virtual CellModeling in Virtual Cell @drbrowncares drbrowncares@gmail.comBrown et al, Frontiers in Neuroscience 2015-2
- 14. Modeling in Virtual CellModeling in Virtual Cell @drbrowncares drbrowncares@gmail.comBrown & Loew, Frontiers in Neuroscience 2015-1
- 15. @drbrowncares drbrowncares@gmail.comBrown & Loew, Frontiers in Neuroscience 2015-1
- 16. @drbrowncares drbrowncares@gmail.comBrown & Loew, Frontiers in Neuroscience 2015-1
- 17. Citations Textbooks (11) + Journal articles (34) @drbrowncares drbrowncares@gmail.com
- 19. Systems Biology Modeling ofSystems Biology Modeling of the Brain in Virtual Cellthe Brain in Virtual Cell Sherry-Ann Brown, MD, PhD @drbrowncares, drbrowncares@gmail.com
Editor's Notes
- Encourage to take pictures of my slides Will be on SlideShare also Want to be interactive: shout responses to questions, laugh, cry, nod your head, clap, etc! And most importantly, think deeply!
- When we stimulate the spine, G protein coupled receptro… blah blah. AND I’m TELLING YOU THIS BECAUSE…These concepts of stimulation of the Purkinje neuron by parallel fibers, or by climbing fibers, or both, resulting in supralinear calcium release...these concepts will come up multiple times throughout this presentation. “Given the importance of Ca21 signaling to the induction of the mechanisms leading to LTD, the objective of this work is to use mathematical models of a Purkinje cell that focus on the relevant Ca21 signaling networks to investigate the significance of certain unique characteristics of the Purkinje cell, such as the sensitivity and density of the IP3R and the geometry of the spines, in terms of LTD induction. The results of this work will aid in identifying those features of the cell that are most critical to the onset of LTD, including consideration of both biochemical and geometrical effects. The wide availability of experimental data on calcium dynamics in Purkinje cells makes such a modeling study feasible.” ~ Hernjak “A recent modeling study of Purkinje spine Ca21 signaling (26) contained analysis of a compartmental model of a single spine that did not consider diffusion out of the spine into the adjacent dendritic shaft or the unique sensitivity and density of the IP3R. These are key differences between the models proposed here and those in the other work. Indeed, it is these features of Ca21 signaling in Purkinje cell spines that set it apart from other systems. As will be shown, without taking into account the unique in vivo sensitivity of the IP3R, significant Ca21 release would be produced at low [IP3] in direct disagreement with available experimental data (e.g., (17)). This combination of biochemical and geometric features also assures that the signal is confined to the activated spine. Additionally, as shown experimentally by Noguchi et al. (25) in pyramidal neurons, diffusion through the spine neck is an important factor in spine Ca21 signaling, suggesting that dynamic spine morphology can be a powerful modulator of synaptic plasticity. The modeling results shown here demonstrate that the spine neck diameter can behave as a sensitive switch for the Ca21 signal.”
- 1D didn’t match 3D model, because did not take PIP2 lateral diffusion into consideration… affects dynamics of the signaling system.
- Changes in pip2 concentration in the membrane of the purkinje cell – red highest blue lowest green baseline - Six spines – simultaneous synthesis of pip2 as well as cleavage of pip2 to give ip3 – looking at a balance of these two processes – with the same sort of stimulus with the same sort of initial conditions in each spine. Lateral diffusion of PIP2 comes into play with spines that have wide necks.
- Models available publicly www.vcell.org https://senselab.med.yale.edu/ModelDB/ShowModel.cshtml?model=126637
- Encourage to take pictures of my slides Will be on SlideShare also Want to be interactive: shout responses to questions, laugh, cry, nod your head, clap, etc! And most importantly, think deeply!