rna level/ transcription rate

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RNA level/ Transcription rate form/activity Enzyme level/ Translation rate Enzyme form/activity Reaction rate Proteins RNAs DNAs level form/ activity rate level form/ activity rate rate

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Reaction rate. rate. Enzyme form/activity. form/activity. Proteins. level. Enzyme level/ Translation rate. rate. form/activity. form/activity. RNAs. level. RNA level/ Transcription rate. rate. DNAs. Inside every organism. food intake. Robust. Organs Tissues Cells Molecules. - PowerPoint PPT Presentation

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Page 1: RNA level/ Transcription rate

RNA level/ Transcription rate

form/activity

Enzyme level/Translation rate

Enzyme form/activity

Reaction rate

Proteins

RNAs

DNAs

level

form/activity

rate

level

form/activity

rate

rate

Page 2: RNA level/ Transcription rate

food intake

Organs

Tissues

Cells

Molecules

Robust

EvolvableEfficient

Inside every organism

Page 3: RNA level/ Transcription rate

Catabolism

Pre

curs

ors

Carriers

Co-factors

Fatty acids

Sugars

NucleotidesAmino Acids

Inside every cell

Page 4: RNA level/ Transcription rate

RNA level/ Transcription rate

DNA level

Biosynthesis

RNA

Gene

Transc.xRNA

RNAp

Pre

curs

ors

Co-factors

Fatty acidsSugars

Nucleotides

Amino Acids

Massively autocatalytic

Page 5: RNA level/ Transcription rate

Cat

abol

ism

AA

RNA

RNAp

Pre

curs

ors

Nucl.

AA

Gene

Transc.xRNA

Page 6: RNA level/ Transcription rate

Cat

abol

ism

AA

tRNA Ribosome

RNA

RNAp

transl. EnzymesPre

curs

ors

Nucl.

AA

Gene

Transc.xRNA

mRNAncRNA

Page 7: RNA level/ Transcription rate

Cat

abol

ism

AA

tRNA Ribosome

RNA

RNAp

Autocatalysis everywhere

transl. Enzymes

xRNAtransc.

Pre

curs

ors

Nucl.

AA

Page 8: RNA level/ Transcription rate

trans.EnzymesAA

mRNAncRNA

tRNA

Ribosome

RNA level/ Transcription rate

RNA form/activity

RNA

Gene

Transc.xRNA

RNAp

productsS reactions

Enz2

P

Enz1 reaction3

Enzyme level/Translation rate

Enzyme form/activity

Reaction rate

Enz2

Page 9: RNA level/ Transcription rate

trans.

ncRNATransc.

productsreactions

reaction3All products feedback

everywhere

These won’t be drawn in

detail

Proteins

Page 10: RNA level/ Transcription rate

trans.EnzymesAA

mRNAncRNA

tRNA

Ribosome

RNA level/ Transcription rate

RNA form/activity

RNA

Gene

Transc.xRNA

RNAp

productsS reactions

Enz2

P

Enz1 reaction3

Enzyme level/Translation rate

Enzyme form/activity

Reaction rate

Enz2

Page 11: RNA level/ Transcription rate

trans.EnzymesAA

mRNAncRNA

tRNA

Ribosome

RNA level/ Transcription rate

RNA form/activity

RNA

Gene

Transc.xRNA

RNAp

S reactionsP

Enz1 reaction3

Enzyme level/Translation rate

Enzyme form/activity

Reaction rate

Enz2

Page 12: RNA level/ Transcription rate

Mature red blood cells

live 120 days

Running only the top layers

productsS reactionsP

Enz1 reaction3 Enzyme form/activity

Reaction rate

Enz2

Page 13: RNA level/ Transcription rate

Genome

Application Diverse

Diverse

Diverse application

s and genomes

Page 14: RNA level/ Transcription rate

Archaea

Eukaryotes

Animals Fungi Plants

Bacteria Algae

What is locus of early evolution?

HGT andShared Protocols

Horizontal gene transfer

Page 15: RNA level/ Transcription rate

Archaea

Eukaryotes

Animals Fungi Plants

Bacteria Algae

DNA levelGene

Controlled, dynamic

HGT andShared Protocols

Horizontal gene transfer

Page 16: RNA level/ Transcription rate

Archaea

Eukaryotes

Animals Fungi Plants

Bacteria Algae

HGT andShared Protocols

trans.EnzymesAA

mRNA

ncRNAtRNARibosome

RNA level/ Transcription rate

RNA form/activity

RNA

Gene

Transc.xRNA

RNAp

productsS reactionsP

Enz1 reaction3

Enzyme level/Translation rate

Enzyme form/activity

Reaction rate

Enz2

Page 17: RNA level/ Transcription rate

Catabolism

Pre

curs

ors

Carriers

Co-factors

Fatty acids

Sugars

NucleotidesAmino Acids

Core metabolism

Page 18: RNA level/ Transcription rate

Co-factors

Fatty acids

Sugars

NucleotidesAmino Acids

Catabolism

Pre

curs

ors

Taxis and transport

Nut

rien

ts

Carriers

Core metabolism

Huge Variety

Same 12

in all cells

Same 8

in all cells

100

same

in all

organism

s

Page 19: RNA level/ Transcription rate

Catabolism

Pre

curs

ors

Carriers

Co-factors

Fatty acids

Sugars

NucleotidesAmino Acids

Core metabolism

Protocols

Constraints that deconstrain

Page 20: RNA level/ Transcription rate

Catabolism

Pre

curs

ors

Carriers

Co-factors

Fatty acids

Sugars

NucleotidesAmino Acids

Core metabolism

Page 21: RNA level/ Transcription rate

Catabolism

Pre

curs

ors

Carriers

Page 22: RNA level/ Transcription rate

Catabolism

TCAPyr

Oxa

Cit

ACA

Gly

G1P

G6P

F6P

F1-6BP

PEP

Gly3p

13BPG

3PG

2PG

ATP

NADH

Page 23: RNA level/ Transcription rate

TCAPyr

Oxa

Cit

ACA

Gly

G1P

G6P

F6P

F1-6BP

PEP

Gly3p

13BPG

3PG

2PG

Pre

curs

ors

metabolites

Page 24: RNA level/ Transcription rate

Enzymatically catalyzed reactions

TCA

Gly

G1P

G6P

F6P

F1-6BP

PEP Pyr

Gly3p

13BPG

3PG

2PG

Oxa

Cit

ACA

Page 25: RNA level/ Transcription rate

TCAPyr

Oxa

Cit

ACA

Gly

G1P

G6P

F6P

F1-6BP

PEP

Gly3p

13BPG

3PG

2PG

ATP

Autocatalytic

NADH

Pre

curs

ors

Carriers

Page 26: RNA level/ Transcription rate

TCA

Gly

G1P

G6P

F6P

F1-6BP

PEP Pyr

Gly3p

13BPG

3PG

2PG

ATP

NADH

Oxa

Cit

ACA

Regulatory

Page 27: RNA level/ Transcription rate

TCAPyr

Oxa

Cit

ACA

Gly

G1P

G6P

F6P

F1-6BP

PEP

Gly3p

13BPG

3PG

2PG

Page 28: RNA level/ Transcription rate

TCA

Gly

G1P

G6P

F6P

F1-6BP

PEP Pyr

Gly3p

13BPG

3PG

2PG

ATP

NADH

Oxa

Cit

ACA

If we drew the feedback loops the diagram would be unreadable.

Page 29: RNA level/ Transcription rate

( )

Mass &Reaction

Energyflux

Balance

dxSv x

dt

Stoichiometry or mass and energy balance

Nutrients Products

Internal

Biology is not a graph.

Page 30: RNA level/ Transcription rate

( )

Mass &Reaction

Mass&Energy Energyflux

Balance

dxSv x

dt

d

dt

Stoichiometry plus regulation

Matrix of integers “Simple,” can be

known exactly Amenable to high

throughput assays and manipulation

Bowtie architecture

Vector of (complex?) functions Difficult to determine and

manipulate Effected by stochastics and

spatial/mechanical structure Hourglass architecture Can be modeled by optimal

controller (?!?)

Page 31: RNA level/ Transcription rate

TCA

Gly

G1P

G6P

F6P

F1-6BP

PEP Pyr

Gly3p

13BPG

3PG

2PG

ATP

NADH

Oxa

Cit

ACA

( )

Mass &Reaction

Energyflux

Balance

dxSv x

dt

Stoichiometry matrix

S

Page 32: RNA level/ Transcription rate

Regulation of enzyme levels by transcription/translation/degradation

TCA

Gly

G1P

G6P

F6P

F1-6BP

PEP Pyr

Gly3p

13BPG

3PG

2PG

Oxa

Cit

ACA

( )

Mass &Reaction

Energyflux

Balance

dxSv x

dt

level

Page 33: RNA level/ Transcription rate

TCA

Gly

G1P

G6P

F6P

F1-6BP

PEP Pyr

Gly3p

13BPG

3PG

2PG

ATP

NADH

Oxa

Cit

ACA

( )

Mass &Reaction

Energyflux

Balance

dxSv x

dt

Allosteric regulation of enzymes

form/activity

Page 34: RNA level/ Transcription rate

TCA

Gly

G1P

G6P

F6P

F1-6BP

PEP Pyr

Gly3p

13BPG

3PG

2PG

ATP

NADH

Oxa

Cit

ACA

Mass &Reaction

( ) Energyflux

Balance

dxSv x

dt

level

form/activity

rate

Page 35: RNA level/ Transcription rate

TCA

Gly

G1P

G6P

F6P

F1-6BP

PEP Pyr

Gly3p

13BPG

3PG

2PG

ATP

NADH

Oxa

Cit

ACA

Fast response

Slow

level

form/activity

rate

Layered architecture

Mass &Reaction

( ) Energyrate

Balance

dxSv x

dt

Page 36: RNA level/ Transcription rate

Enzyme level/Translation rate

Enzyme form/activity

Reaction rate

Proteins

RNAs

DNAs

level

form/activity

rate

Control of

protein levels

Page 37: RNA level/ Transcription rate

RNA level/ Transcription rate

form/activity

Enzyme level/Translation rate

Enzyme form/activity

Reaction rate

Proteins

RNAs

DNAs

level

form/activity

rate

level

form/activity

rate

rate

Page 38: RNA level/ Transcription rate

RNA level/ Transcription rate

DNA level

RNA

Gene

Transc.xRNA

RNAp

Transcription

Page 39: RNA level/ Transcription rate

RNA level/ Transcription rate

DNA level

RNA level

RNA

Gene

Transc.xRNA

RNAp

product

Enz

Controlled, dynamic

Page 40: RNA level/ Transcription rate

RNA level/ Transcription rate

DNA level

RNA

Gene

Transc.xRNA

RNAp

trans.EnzymesAA

mRNA ncRNAtRNA

Pre

curs

ors

Nucl.

AA Enzyme level/Translation rate

Page 41: RNA level/ Transcription rate

trans.EnzymesAA

mRNA

ncRNAtRNARibosome

RNA level/ Transcription rate

RNA form/activity

RNA

Gene

Transc.xRNA

RNAp

productsS reactionsP

Enz1 reaction3

Enzyme level/Translation rate

Enzyme form/activity

Reaction rate

Enz2

Page 42: RNA level/ Transcription rate

RNA level/ Transcription rate

RNA form/activity

Enzyme level/Translation rate

Enzyme form/activity

Reaction rateWhat to call

the sublayers?

level

form/activity

rate

What is where

Page 43: RNA level/ Transcription rate

Genes

Co-factorsFatty acidsSugars

Nucleotides

Amino Acids

Polymerization and complex

assemblyP

roteinsP

recu

rsor

s

Autocatalytic feedback

Taxis and transport

Nut

rien

ts

Core metabolism

DNA replication

Trans*

Cat

abol

ism

Carriers

100 104 to ∞in one

organisms

Huge Variety

12

8

Page 44: RNA level/ Transcription rate

Polymerization and complex

assembly

Autocatalytic feedback

Genes

ProteinsDNA

replication

Trans*

104 to ∞in one

organismsHuge

VarietyFew polym

erases

Highly conserved