genetic switch between redundancy and synergy in a multicellular gene expression code - giovanni...
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Genetic switch between redundancy and synergyin a multicellular gene expression code
Giovanni Diana
MRC Centre for Developmental NeurobiologyKing’s College London
Quantitative Laws II13 June 2016
From environment to physiology
Environment
Gene expression
Physiology
daf-7 and tph-1 expression in sensory neurons of C. elegans
egg-5RNAi
BaselineBacteria Food ShiftWell Fed
40x
RNAi Food ShiftWell fedBaseline
food
Two g
enera
tions
Hatc
h Day of Adulthood
1 2 3 5 64L4
Imaging
Microfluidic system for high-throughputin vivo imaging of C. elegans
NSM ADF ASItph-1 tph-1 daf-7Gene:
Neuron:
Fluorescence images reporting tph-1/daf-7 promoter activities
Food Level (cells/ml)100 102 104 106 108 1010
Wild Typedaf-7(-)tph-1(-)tph-1(-);daf-7(-)
25
20
30
35
40
45
Mean L
ifesp
an (
days)
daf-7 and tph-1 regulate lifespan response to food in the environment
Food Level
tph−1 in ADFdaf−7 in ASI
tph−1 in NSMEx
pres
sion
Lev
el
Food Leveltph−1 variance in ADFdaf−7 variance in ASItph−1 variance in NSM
Vari
an
ce Wild type
daf-7 KO
daf-7 regulate expression noise.
Information theory and molecular genetics
Information encodedby each neuron Channel capacity
wholesum of parts
Info
rmat
ion
(bits
)
0
1
2
−0.4
0.4
Frac
tion
ofR
edun
dant
Info
rmat
ion
−0.4
0.4
Red
unda
ncy
Syne
rgy (b
its)
wild-typ
e
tph-1(
–)
daf-7
(–)
tph-1(
–); da
f-7(–)
Info
rmat
ion
Whole Sumof Parts<
Redundancy
Whole Sumof Parts>
Synergy
ASI
ADF
NSM
Combinationof NSM, ASI,and ADF Si
gnal
Cor
rela
tion
(bits
)
0
0.4
0.8
0.4
0
wild-type
daf-7(-)
tph-1(-)
tph-1(-);daf-7(-)
Sig
nal C
orr
ela
tion
Noise Correlation
input
output
= {0,1}
S1 S2 S3
= αS1+ βS2+ γS3
Sensors
0.0 0.5 1.0 1.5 2.00.0
0.2
0.4
0.6
0.8
1.0
Signal/Noise Ratio, σ3/a
Frac
tion
daf-7 is required to maintaina redundant coding strategy
SynergyRedundancy
Information transmitted by3-node gaussian networks
Constraining information generates synergy switches at low SNR
single and double mutants display high noise correlation
Conclusion and Outlook
I The ADF-ASI-NSM network provides a robustcode for food abundance in the environment.
I daf-7 is required to maintain redundancy in theencoding.
I How does the system perform at differenttemperatures.
I Link coding strategy to network topology.
Acknowledgements
KCLDr. QueeLim Ch’ngDr. Eugeni V. EntchevDr. Dhaval S. PatelOwen LeyshonKatherina Gers-BarlagBrian HandleyHale Tunbak
Georgia Institute ofTechnology:Dr. Hang LuDr. Mei Zhan