1. Digital Cells Foothill College Nanotechnology Image by John Alsop
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6. Fundamental Interactions There are three ‘semi-distinct’ layers of process and information space inside a cell – connected through molecular networks
7. The (Really) Big Picture Ion Channels Receptors Transcription Factors Ligands ELECTROPHYSIOLOGY Extracellular space Cytoplasm Nucleus Translation + processing cis sites Intracellular Signaling Genetic Regulatory Network mRNA
10. Genomic Decision Networks Simplified version of the phage decision network that determines whether an infected E. coli cell follows the lytic or lysogenic pathway. Dashed arrows indicate the direction of transcription, and bold arrows indicate regulatory interactions between a gene product and particular DNA region.
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13. Mechanics of Transcription Genes rely on several molecular signals and processes to manifest a solution, which is part of a larger decision network
18. Information vs. Processing Just as in a computer, data bits and processing bits are made from the same material, 0 or 1, or A, T, C, G, or U in biology
19. Basic GRN Circuits Gross anatomy of a minimal gene regulatory network (GRN) embedded in a regulatory network. A regulatory network can be viewed as a cellular input-output device. http://doegenomestolife.org/
24. Digital Cell Circuit (1) INVERSE LOGIC. A digital inverter that consists of a gene encoding the instructions for protein B and containing a region (P) to which protein A binds. When A is absent (left)—a situation representing the input bit 0—the gene is active. and B is formed—corresponding to an output bit 1. When A is produced (right)—making the input bit 1—it binds to P and blocks the action of the gene—preventing B from being formed and making the output bit 0. Weiss http://www.ee.princeton.edu/people/Weiss.php
25. Digital Cell Circuit (2) In this biological AND gate, the input proteins X and Y bind to and deactivate different copies of the gene that encodes protein R. This protein, in turn, deactivates the gene for protein Z, the output protein. If X and Y are both present, making both input bits 1, then R is not built but Z is, making the output bit 1. In the absence of X or Y or both, at least one of the genes on the left actively builds R, which goes on to block the construction of Z, making the output bit 0. Weiss http://www.ee.princeton.edu/people/Weiss.php
30. Diagram Proposal by A.Funashi & H.Kitano ERK ERK Ras PDK-1 ERK ERK ERK RSK RSK RSK RSK RSK CREB c-Myc c-Myc Raf Ras Raf Raf MEK MEK ERK ERK CREB P P P P * * P P P P P P P P P P P P P P P P P Process Diagram
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32. Notation of the Process Diagram A State transition – changes the state of modification rather than activation Activation Inhibition Translocation of module Dashes line indicates active state of a molecule Specific state of molecular species A
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36. Symbols / Conventions used in eMIMs A B A B C Ph’tase A A X Y Protein A and B can bind to each other The node represents the A:B complex Multimolecular complex: x is A:B; y is (A:B):C Endless extendable Reactions: P P A B Covalent modification of protein A. A can exist in a phosphorylated state. Cleavage of a covalent bond: dephosphorylation of A by a phosphatase. Stoichiometric conversion of A to B .
37. Symbols / Conventions used in eMIMs A A Reactions: Cytosol Nucleus Contingencies: Transport of A from cytosol to nucleus. The dot represents A after transport to the nucleus. Formation of homodimer. Dot on the right represents copy of A . Dot on line represents the homodimer A:A Enzymatic stimulation of a reaction Enzymatic of a reaction in trans. Stimulation of a process. Bar indicates necessity. Inhibition Transcriptional activation Transcriptional inhibition