QUANTITATIVE LAWS June 13 -June 24

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. From environment to physiology
Environment
Gene expression
Physiology

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. 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. 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. 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