Gene Silencing

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Gene Silencing

• Bob Anderssen
• CSIRO Mathematical and Information Sciences
• Peter Waterhouse
• CSIRO Plant Industry
• Thanks to various CMIS and CPI colleagues.

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Contents

• What is Gene Silencing?
• The Natural Mechanism Virus Control and
  Developmental Control
• (An Emergence Complex System Science
  Phenomenon)
• Scientific Exploitation Knockouts and Knockdowns
• The Basic Ordinary Differential Equation Model
• Easy to write down complex models and solve
  (Maple)
• Mathematical Experimentation utilizing Plant
  Breeding Data
• Opportunities
• New mutants using knockouts.
• Designing knockout strategies (Combinatorial
  Optimization CMIS)
• Designing new plant architecture.
• How can Complex System Science assist?

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dsRNA mediated gene silencing
Dicers
Argonautes
Bind mRNA
Cleavage
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Opportunities for CSS
AG04
24nt
dsRNA templates
DCL3
DCL4
DCL2
DCL1
22nt
21nt
21nt
siRNA
siRNA
miRNA
AG0
AG0
AG01
mRNA cleavage
Virus RNA cleavage
mRNA cleavage
Developmental regulation
Viral defence
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Viral Control (left hand side)
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RNAi mechanism Mimicking Viral Control
mRNA
dsRNA
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RNAi mechanism
cD
mRNA
dsRNA
cS
AAAAAAA-
siRNA
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RNAi mechanism
mRNA
dsRNA
AAAAAAA-
siRNA
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RNAi mechanism
mRNA
dsRNA
AAAAAAA-
siRNA
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The Basic Ordinary Differential Equation Model
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MapleMathematical Experimentation Steady
State Ranking
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The Opportunity

• Gene Knockout Introduce dsRNA as hairpin RNA
  (hpRNA) to silence some specific gene.
• Trick the plant in to shutting down or re-routing
  specific molecular pathways to alter biological
  activities.
• e.g. - flowering time
• - leaf shape
• - yield index
• - oil quality

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(No Transcript)
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Synthetic miRNAs
CUC1/2 syn miRNA
Wt
CUC1/2 syn miRNA
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How can CSS assist?

• Designing Knock/Knockdown Strategies
  (combinatorial optimization CMIS)
• Assist with the Biological and Mathematical
  Challenges as they Unfold.

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Gene Silencing Pathways in Plants
Heterochromatin formation
AG04
24nt
dsRNA templates
RDR6
DCL3
DCL4
DCL2
DCL1
22nt
21nt
21nt
siRNA
miRNA
ta-siRNA
mRNA cleavage
Virus RNA cleavage
mRNA cleavage
Developmental regulation
Viral defence
Control of developmental timing
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Evolutionary tree of dicer genes in plants
Giardia
2,300
Large scale gene duplication
Time in million years (My)
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Gene Silencing Pathways in Arabidopsis(Choose an
appropriate Biological Model System)
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3
1
4
1
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Thank you for your attention!

• What is Gene Silencing?
• The Natural Mechanism Virus Control and
  Developmental Control
• (An Emergence Complex System Science
  Phenomenon)
• Scientific Exploitation Knockouts and Knockdowns
• The Basic Ordinary Differential Equation Model
• Easy to write down complex models and solve
  (Maple)
• Mathematical Experimentation utilizing Plant
  Breeding Data
• Opportunities
• New mutants using knockouts.
• Designing knockout strategies (Combinatorial
  Optimization CMIS)
• Designing new plant architecture.
• How can Complex System Science assist?