1. Computational Biology, Part 26 Virtual Cell Robert F. Murphy Copyright  2005,2006. All rights reserved.

2. Virtual Cell - NRCAM http://www.nrcam.uchc.edu/vcellR4/login/login.jsp Framework for building and running models of cell biological processes Framework for building and running models of cell biological processes Built in support for describing compartments, biochemical species, electrophysiological phenoma Built in support for describing compartments, biochemical species, electrophysiological phenoma Models can incorporate empirically derived geometries for compartments Models can incorporate empirically derived geometries for compartments Models saved and calculated on the server Models saved and calculated on the server

3. Virtual Cell - To do Create account Create account Read User Guide Read User Guide

4. Virtual Cell - Hodgkin-Huxley Versions of the models in “Computational cell biology” by Fall et al have been implemented in Virtual Cell Versions of the models in “Computational cell biology” by Fall et al have been implemented in Virtual Cell These are available as Public models These are available as Public models Within Virtual Cell, use Open/Biomodel Within Virtual Cell, use Open/Biomodel Then open Model Neighborhood/CompCell/Hodgkin-Huxley Then open Model Neighborhood/CompCell/Hodgkin-Huxley

13. Model Descriptions Virtual Cell supports exporting (and to a limited extent, importing) model descriptions in various XML formats Virtual Cell supports exporting (and to a limited extent, importing) model descriptions in various XML formats  SBML (Systems Biology Markup Language, uses MathML)  CellML  VCML (Virtual Cell Markup Language) - required to re-import full model

14. SBML Models electrical behavior of the squid giant axon. Used to demonstrate interacting ion channels. Described in 2.5. Models electrical behavior of the squid giant axon. Used to demonstrate interacting ion channels. Described in 2.5. Models electrical behavior of the squid giant axon. Used to demonstrate interacting ion channels. Described in 2.5. Models electrical behavior of the squid giant axon. Used to demonstrate interacting ion channels. Described in 2.5.

15. SBML 100.0 100.0 taum taum 40.0 40.0 V V 1.0 1.0 1.0 1.0

16. CellML

17. CellML Models electrical behavior of the squid giant axon. Used to demonstrate interacting ion channels. Described in 2.5. Models electrical behavior of the squid giant axon. Used to demonstrate interacting ion channels. Described in 2.5.</Ann\otation> K K Na Channel H Gate (Open) Na Channel H Gate (Open) Na Na Na Channel M Gate (Open) Na Channel M Gate (Open)

18. Building a simulation To illustrate building a new simulation, we will build a model in which To illustrate building a new simulation, we will build a model in which  Prohormone is initially outside a cell,  Prohormone is internalized into the cell,  Prohormone is converted to hormone  Hormone is exported from the cell

19. Building a simulation Define a Cell compartment Define a Cell compartment Rename unnamed compartment to Extracellular Rename unnamed compartment to Extracellular Add a species “prohormone” to Extracellular Add a species “prohormone” to Extracellular Add a species “hormone” to Extracellular Add a species “hormone” to Extracellular Copy species “prohormone” to Cell Copy species “prohormone” to Cell Copy species “hormone” to Cell Copy species “hormone” to Cell

20. Building a simulation Right (control) click on Cell membrane Right (control) click on Cell membrane Define a flux for prohormone as “0.1*prohormone_Extracellular” Define a flux for prohormone as “0.1*prohormone_Extracellular” Define a flux for hormone as “- 1.0*hormone_Cell” Define a flux for hormone as “- 1.0*hormone_Cell” Right (control) click on Cell Right (control) click on Cell Define a reaction for prohormone to hormone with mass action forward rate=1.0 and reverse rate=0.0 Define a reaction for prohormone to hormone with mass action forward rate=1.0 and reverse rate=0.0

21. Building a simulation Define a new Application Define a new Application Give initial value for prohormone_Extracellular as 10.0 Give initial value for prohormone_Extracellular as 10.0 Run model Run model

22. Models that consider compartment geometry Virtual Cell facilitated Ca-diffusion model from tutorial Virtual Cell facilitated Ca-diffusion model from tutorial

23. Making a compartment map for Virtual Cell from a fluorescence microscope image Start from a fluorescence microscope image of a lysosomal protein (LAMP-2) Start from a fluorescence microscope image of a lysosomal protein (LAMP-2)

24. Making a compartment map for Virtual Cell from a fluorescence microscope image Use Matlab to create an image with values of zero for background, one for cytoplasm, and two for lysosomes Use Matlab to create an image with values of zero for background, one for cytoplasm, and two for lysosomes Assume that the autofluorescence in the lysosome image is sufficient to find a region corresponding to the cytoplasm Assume that the autofluorescence in the lysosome image is sufficient to find a region corresponding to the cytoplasm

25. Make contiguous cytoplasm image by averaging weak autofluorescence img=imread('r06aug97.h4b4.13--1---2.dat.png');a=double(img);b=(a-min(min(a)))./(max(max(a))-min(min(a)));H=fspecial('average',13);c=imfilter(b,H,'replicate');d=im2bw(c,0.004);imshow(d);max(max(d))

26. Combine with image of pixels with positive lysosomal staining e=im2bw(b,graythresh(b));imshow(e); f=d + e; imshow(f,[0 2]); g=uint8(f);imwrite(g,'geomap.tif','TIF','Compression','none');

27. Resulting image