Design Principles in Biology:

tastelesscowcreekBiotechnology

Oct 4, 2013 (3 years and 9 months ago)

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Design

Principles

in
Biology
:

a
consequence

of
evolution

and natural
selection



Rui

Alves

University

of Lleida

ralves@cmb.udl.es

Climbing

down

mount

improbable


Overtime
,
edged

stones

would



accumulate

on

the

slope
.


Smooth
, round,
stones

accumulate

at
the


bottom
.



Design

Principles
:

-

Smooth
,
roundish

rocks

roll
down

the

mountain
.

-

Edged
, flat,
rocks

don’t
.

Design principles in molecular biology



Similarly, if a topology or set of parameters
can be shown to create a molecular network
that functionally outperforms all other
possible alternatives in a given set of
conditions, one can talk about a design
principle for the system under those
conditions.

[
sensu

engineering]

Index

of
talk



How to identify design principles in molecular
networks


Design principles in:


Gene expression


Metabolic networks


Signal transduction


Development


Design principles, what are they good for?


Summary


First step, define the alternatives



Gene

Regulator

+

Gene

Regulator

_

X0


X1


X2


X3

X0


X1


X2


X3

First step, define the alternatives



X0


X1


X2


X3

X3

t

How strong should the feedback be?

Then, create models for each alternative



Gene

Regulator

+

Gene

Regulator

_

Then, create models for each alternative



X0


X1


X2


X3

X0


X1


X2


X3








Characterization

of
network

behavior

Biological functional effectiveness
criteria for the network
.








Alternative

designs

X1 …
Xj



X1 …
Xj





Mathematical models






Enforce mathematical controls
before analyzing model behavior








Comparison

of
behavior

between

networks

Index

of
talk



How to identify design principles in molecular
networks


Design principles in:


Gene expression


Metabolic networks


Signal transduction


Development


Design principles, what are they good for?


Summary


The demand theory for gene expression



Are there situations where positive regulation
of gene expression outperforms negative
regulation of gene expression and vice versa?

Gene

Regulator

+

Gene

Regulator

_

Regulating gene expression has principles


Positive regulator:


More effective when gene product in demand for large
fraction of life cycle.


Less noise sensitive if signal is low.


Negative regulator:


More effective when gene product in demand for small
fraction of life cycle.


Less noise sensitive if signal is high.


Gene

Regulator

+

Gene

Regulator

_

Genetics

149:1665; PNAS 103:3999; PNAS 104:7151;
Nature

405
: 590

Glycogen
Trehalose

Regulating gene expression has principles

Design principles in development

Design principles in development

Index

of
talk



How to identify design principles


Design principles in:


Gene expression


Metabolic networks


Signal transduction


Development


Design principles, what are they good for?


Summary


Negative overall feedback is a design principle in
metabolic biosynthesis



X0


X1


X2


X3


Negative overall feedback:


More effective in coupling

production to demand.


More robust to fluctuations.

Bioinformatics

16:786;
Biophysical

J. 79:2290

Index

of
talk



How to identify design principles


Design principles in:


Gene expression


Metabolic networks


Signal transduction


Development


Design principles, what are they good for?


Summary


Bifunctional

sensors can be a design principle in
signal transduction




Bifunctional

sensor:


Performs best against cross talk


Independent deactivator:


Better integrator of signals


Mol.
Microbiol
. 48:25; Mol.
Microbiol
. 68: 1196

Signal

Sensor

Sensor

Efector

Efector

Deactivator

Effect

Index

of
talk



How to identify design principles


Design principles in:


Gene expression


Metabolic networks


Signal transduction


Development


Design principles, what are they good for?


Summary


Gene

Regulator

_

Design principles in development

Gene

Regulator

+

High

demand
,
low

signal

Signal

+

High

demand
,
high

signal

Low

demand
,
high

signal

Low

demand
,
low

signal

Signal

_

Genetics

149:1665; PNAS 103:3999; PNAS 104:7151;Nature

405: 590

Index

of
talk



How to identify design principles


Design principles in:


Gene expression


Metabolic networks


Signal transduction


Development


Design principles, what are they good for?


Summary


Biological design principles are good to
understand why biology works as it does


Biological design principles may connect
molecular determinants to functional
effectiveness.

Heat

shock

Expression

of
important

genes

time

Growth

rate

time

BMC
Bioinformatics

7:184

Underlying assumption


Evolution of molecular networks can be
treated as modules.


Work in the group of Uri
Alon

suggests that


networks evolving to meet simultaneous goals
evolve in a modular fashion


Networks evolving to meet a single goal evolve
globally


Modularity seems like a reasonable first
assumption

PNAS 102:13773; PLOS
Comp

Biol

4:e1000206;
BMC
Evol

biol

7
: 169

The good news about function


Sometimes, you get stuff for free!!!



For example:



networks that are responsive to signals, just because
they are responsive may have inbuilt buffering of
noise.


Functions that are associated with marginally stable
proteins are favored because due to the large
dimensions of sequence space most randomly
selected sequences have a structure that is marginally
stable.

PNAS 100:14463; PNAS 103:6435;
Proteins

46:105

How can biological design principles be
applied?


Design of molecular circuits with specific
behaviors!!

Stable

Systems

Unstable

systems

Oscilations

Bistable

systems

Cell

113: 597;
PLoS

Comput

Biol
. 5:e1000319; PNAS 106: 6435

Index

of
talk



How to identify design principles


Design principles in:


Gene expression


Metabolic networks


Signal transduction


Development


Design principles, what are they good for?


Summary


Summary


Design principles can be found in molecular
networks.


Such principles can sometimes be connected
to selection for function effectiveness.


Even in the absence of such a connection, if
they are valid they can be used to build
biological circuits with specific behaviors.


Acknowledgments

Mike
Savageau

Albert
Sorribas

Armindo

Salvador

Oleg
Igoshin

Programa

Ramon y
Cajal

MCyT

MCyT

FCT

NIH