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Genetic switch between redundancy and synergy in a multicellular gene expression code - Giovanni Diana

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QUANTITATIVE LAWS
June 13 -June 24

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Genetic switch between redundancy and synergy in a multicellular gene expression code - Giovanni Diana

  1. 1. Genetic switch between redundancy and synergy in a multicellular gene expression code Giovanni Diana MRC Centre for Developmental Neurobiology King’s College London Quantitative Laws II 13 June 2016
  2. 2. From environment to physiology Environment Gene expression Physiology
  3. 3. daf-7 and tph-1 expression in sensory neurons of C. elegans egg-5 RNAi Baseline Bacteria Food ShiftWell Fed 40x RNAi Food ShiftWell fed Baseline food Twogenerations Hatch Day of Adulthood 1 2 3 5 64L4 Imaging Microfluidic system for high-throughput in vivo imaging of C. elegans NSM ADF ASI tph-1 tph-1 daf-7Gene: Neuron: Fluorescence images reporting tph-1/daf-7 promoter activities Food Level (cells/ml) 10 0 10 2 10 4 10 6 10 8 10 10 Wild Type daf-7(-) tph-1(-) tph-1(-);daf-7(-) 25 20 30 35 40 45 MeanLifespan(days) daf-7 and tph-1 regulate lifespan response to food in the environment Food Level tph−1 in ADF daf−7 in ASI tph−1 in NSM ExpressionLevel Food Level tph−1 variance in ADF daf−7 variance in ASI tph−1 variance in NSM Variance Wild type daf-7 KO daf-7 regulate expression noise.
  4. 4. Information theory and molecular genetics Information encoded by each neuron Channel capacity wholesum of parts Information (bits) 0 1 2 −0.4 0.4 Fractionof Redundant Information −0.4 0.4 RedundancySynergy (bits) w ild-type tph-1(–) daf-7(–) tph-1(–);daf-7(–) Information Whole Sum of Parts < Redundancy Whole Sum of Parts > Synergy ASI ADF NSM Combination of NSM, ASI, and ADF SignalCorrelation (bits) 0 0.4 0.8 0.4 0 wild-type daf-7(-) tph-1(-) tph-1(-);daf-7(-) SignalCorrelation Noise Correlation input output = {0,1} S1 S2 S3 = αS1+ βS2+ γS3 Sensors 0.0 0.5 1.0 1.5 2.0 0.0 0.2 0.4 0.6 0.8 1.0 Signal/Noise Ratio, σ3/a Fraction daf-7 is required to maintain a redundant coding strategy SynergyRedundancy Information transmitted by 3-node gaussian networks Constraining information generates synergy switches at low SNR single and double mutants display high noise correlation
  5. 5. Conclusion and Outlook The ADF-ASI-NSM network provides a robust code for food abundance in the environment. daf-7 is required to maintain redundancy in the encoding. How does the system perform at different temperatures. Link coding strategy to network topology.
  6. 6. Acknowledgements KCL Dr. QueeLim Ch’ng Dr. Eugeni V. Entchev Dr. Dhaval S. Patel Owen Leyshon Katherina Gers-Barlag Brian Handley Hale Tunbak Georgia Institute of Technology: Dr. Hang Lu Dr. Mei Zhan

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