# Design Principles in Biology:

Biotechnology

Oct 4, 2013 (4 years and 7 months ago)

239 views

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

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

Oleg
Igoshin

Programa

Ramon y
Cajal

MCyT

MCyT

FCT

NIH