Table of Contents

vivaciousaquaticAI and Robotics

Nov 13, 2013 (3 years and 9 months ago)

84 views

ISBE working paper 3
.0


ISBE:

Infrastructure for Systems Biology Europe

Table of Contents


1

An Infrastructure for Systems Biology Europe

................................
................................
......

1

1.1

Why is Systems Biology needed?

................................
................................
..................

1

1.2

What’s new in the proposal?

................................
................................
..........................

2

1.3

What is the purpose of Systems Biolo
gy?

................................
................................
......

2

1.4

What is the role of Systems Biology?

................................
................................
.............

2

1.5

How will Systems Biology help?

................................
................................
.....................

3

1.6

How much will it cost?

................................
................................
................................
...

3

2

A distributed research infrastructure, ISBE, is needed urgently for Biology

..........................

3

3

The dynamic infrastructure of European Systems Biology

................................
....................

4

4

Focus

................................
................................
................................
................................
...

5

5

The different branches of the ISBE: TAP, i.e. Tools, A
ctivities & People

..............................

6

5.1

Tools

................................
................................
................................
..............................

6

5.1.1

Connecting to model generation methodologies

................................
...................

6

5.1.2

Connecting to experimental design methodologies

................................
...............

6

5.1.3

Connecting to component
-
data generation methodologies

................................
...

6

5.1.4

Connecting to technology development

................................
................................

6

5.1.5

Connecting to physiological expertise

................................
................................
...

7

5.1.6

Connecting to data
and software management facilities

................................
.......

7

5.1.7

Connecting to data analysis and data management methodologies

......................

7

5.2

Activities

................................
................................
................................
........................

7

5.2.1

Real
-
time, cross
-
laboratory data generation

................................
.........................

7

5.2.2

Real
-
time, cross
-
laboratory modelling

................................
................................
...

7

5.2.3

Real
-
time, cross
-
laboratory model validation

................................
........................

8


2



5.2.4

Real
-
time, cross
-
laboratory data integration & curation and model integration &
curation
................................
................................
................................
.................

8

5.2.5

Dynamic standardisation

................................
................................
......................

8

5.3

People

................................
................................
................................
...........................

8

5.3.1

Personnel Training and Ed
ucation

................................
................................
........

8

5.3.2

Methodology and iterative calibration on what is needed for Europe

.....................

9

5.3.3

Meetings

................................
................................
................................
...............

9

5.3.4

Work
-
workshops and jamborees
................................
................................
...........

9

5.3.5

Platforms linking with industry

................................
................................
...............

9

5.3.6

Embassi
es

................................
................................
................................
............

9

6

Management

................................
................................
................................
......................

10

7

Timing

................................
................................
................................
................................

10


1



Executive Summary

This paper
outlines

the
proposal for an Infr
astructure for Systems Biology in Europe (
ISBE
)
, a
unique type of distributed infrastructure that
is designed to meet the needs of

European Systems
Biology
,

both in terms of development and its applications.

Systems Biology requires the
simultaneous and hi
ghly interactive implementation of a
large

number of multiple and diverse

activities
. These range from
mathematical
and formal
modelling to biological and clinical
experiments,
to
technology development. For each medical/biological/biotechnological problem

to be
addressed, the optimal combination of activities is different.

The total array of activities is
so
large,

and the needs so dynamic, that
it
cannot be
undertaken a
t a

single location


whilst
simultaneously delivering optimal quality and efficiency.

Focus of ISBE:

Answering the question
-

how the interaction of biological components lead
s

to
the functioning of living organisms in a constantly changing environment
?



Structure of ISBE
:

We are proposing a
widely distributed, branched infrastructure
com
prising
interconnected hubs


where each
hub (ISBE
Institutions/
Centres) focuses on an area of
S
ystems
B
iology
.

For example,
model organism
s
, model cell population
s
, disease,
biotechnology, ecology & green biology
. In addition, the infrastructure will incl
ude technological
expertise; for example,

stochastic computation,
algorithmic modelling,
inverse modelling
and
high throughput data generation
.

Infrastructure repositories
will focus on data storage and
handling, as well as
standardisation
.
It is envisaged

that

individual
research laboratories
will
participate in

the ISBE

by
contributing more focused expertise

-

but
using the potential offered
by the infrastructure for technology
development

etc.


Impact of ISBE:

The aim of the ISBE will be

t
o systematicall
y understand complex biological
processes

and to develop technologies
. This will
transform

basic knowledge of complex
molecular systems into the new area of predictive, preventive and
personalised
medicine. In
addition, systems biology approaches will prov
ide new insights and
assist the development of

tools for the design of new biotechnological and environmental applications
.

The
objective is to
transform European
S
ystems
B
iology into a world
-
wide activity by the use of web
-
based
experimental facilities an
d live mathematical modelling
. It is envisaged that this will make the
science

more productive, cost
-
efficient and useful for European
S
ociety.


T
he creation of such an infrastructure

will require
detailed planning and
management


with the
need for

a prep
aratory phase.

1

An
Infrastructure for Systems Biology Europe

1.1

Why

is

Systems Biology

needed

for modern life
-
science research
?

The
impact of European research in the
l
ife
s
ciences

for
the benefit of
society and industry has
been
significant
less than expecte
d. To a large extent this is due to the complexity of living
organisms
,

in terms of both the number of interacting components and the essential
nonlinearities of the interactions. Systems
B
iology sits
at the frontier of
research in the
life
sciences
. It is

a highly interdisciplinary approach
to the
study

of
biological complexity in health
and disease.
Over

the past 20 years it has become clear that
the understanding of biological

2



systems is central to life science
. Sing
le molecules may contribute to l
ife, b
ut are not
, in

themselves
,

alive.

Medicine
today

focuses

on the
systematic
diagnosis
and treatment of
‘multifactorial’
(
and hence elusive
)

diseases

-

as
opposed
to
the
traditional
,

single molecule
,

targeted approach.

Hence
, new Systems Biology Infrastructu
res
,

capable of supporting
technology transfer
,

as well as translating scientific and medical discoveries into
medicine
and
related areas
,

will improve both
the
basic understanding of life and Medicine
.

It will also
enhance
the economic potential of Europe
.

The Systems Biology

enabled by the
proposed
ISBE
(
described in

this paper
)
stand
s

a
real

chance of
significantly
increasing the
quality and
effectiveness

the science in areas such as health, green and white biotechnology, bio
-
energy
and ecology.


1.2

What’s
new

in the proposal
?

The

increasing pace

of
advances in molecular biology, biotechnology and medicine
is
driven by
interdisciplinary research

-

which
combines
experimental molecular biology, clinical research,
bioinformatics, computational biology, mathema
tics, computer science, physics, chemistry and
biological engineering in an approach
called
Systems Biology.

Systems Biology is a new way of
doing science
,

demanding new intellectual and
organisational
structures to deliver its full
potential.
It
requires
the combined implementation of computational and experimental
approaches

(
which is novel for most molecular biological sciences
)
.
Simultaneously, it
addresses (a)
the complexity of networks

-

which are,
ultimately
,

as large as entire expressed
genomes
; and

(b)
precise, experimentally determined interactive properties of the molecular
constituents
.

This approach has, hitherto
,

only been applied in

engineering and
the
physical
sciences.
In addition,
Systems

Biology
is amenable to
studying

molecular interactio
ns

in more
clinical and biotechnological settings. The task of Systems Biology is to integrate
accurate
experimental
data
with
predictive models of life in health and disease.
The
challenge
for
interdisciplinary research
is to
integrate

the

experimental, c
omputational and theoretical
sciences
.

1.3

What

is the purpose of Systems Biology
?

Systems Biology integrates high
-
throughput technologies, model systems, molecular biology,
biochemistry, engineering, information technologies, bioinformatics, clinical research

and
innovative engineering to understand how biological function emerges from interacting biological
components.

Such
integration can only be achieved through a certain critical mass of
experimentation, such as in genomics, and with the help of mathematic
al analyses, modelling,
informatics and statistics.

Biological networks, both intracellular and in
-
and
-
between whole cells,
tissues and organisms, connect thousands of molecular and higher
-
order functions, such that
the
functioning of any part of the netwo
rk depends on different, remote parts.


1.4

What
is the role
of
Systems Biology
?

Most biological processes governing health or disease (metabolic, sport, developmental, cancer,
cardiovascular, neurodegenerative
et cetera
) involve complex interaction

networks

between
hundreds of genes and proteins.

Invariably, the complexity is enormous and every case
becomes different
. This
necessitat
es

the integration of experimental
,

quantitative data on a
systems
-
wide level to obtain information about the state, dynamics an
d variability of living cells,

3



organs, organisms and populations.

The goal is to
standardise
these approaches and integrate
them into predictive models.

This
also relates
to the understanding and promotion of health and
the retardation of ageing, as well a
s to diagnosis (e.g. through novel biomarking strategies) and
therapies (e.g. using new network targeting drugs).

Whilst
the latter is directly relevant to red
biotechnology, the same issues apply to nutrition and white biotechnology (e.g. engineering
fung
i to produce more and better antibiotics
),
to green biotechology (e.g. engineering plants
towards the production of food in more efficient and carbon dioxide neutral ways), as well as to
the fields of bio
-
energy (e.g. better ways to produce bioethanol from

plant waste) and ecology
(e.g. reducing the escape of NO and N
2
O from waste treatment plants, or methane from cattle).

1.5

How

will Systems Biology help
?

Mathematical modelling and analysis can contribute, but both require meticulous and
quantitative experime
ntation to provide precise and useful data.

Because so many experimental
conditions and approaches are possible, model driven experimental design and control can
make

important

experiments much more
effective and
meaningful.

Ultimately, the ability to carr
y
out experiments steered in real time by modelling, and
vice versa
,
will

greatly empower S
ystems
B
iology and
achieve, in
many
areas
of its
application, far
great
er

impact on health and
the
economy.


The
capacity
to
achieve the
objectives

outlined above,

a
re
,

in principle
,

available in Europe

-

but
the infrastructure is fragmented.

For

any Systems Biology problem to be addressed, numerous
state
-
of the
-
art methodologies need to be implemented and integrated with new methodologies
and
standardisation
procedur
es

(which have to be developed)
.

T
hese methodologies are
currently
available
,

or under development
,

in individual centres or laboratories in
various
European countries.

An
important role of ISBE will be
to identify, structure
and support of large
-
scale res
earch projects

on, for example,
multifactorial diseases, bioenergy

and
bio
-
manufacturing
.

Such projects
are currently beyond the capability of single European Institutions.

In parallel, the ISBE will provide support to individual laboratories and small
e
r m
edium size
consortia that have succeeded in national or European grant applications

1.6

H
ow much

will it cost
?

The

creation

of the new infrastructure will involve
significant

cost, both in terms of installing
connections between existing centres and funding n
ew and
required
activities

in

existing
centres.

However, such a development

will ultimately
result in
considerable
savings. Since

the
ISBE will connect all
the
expertise and facilities

in Europe
, there will be a

large

reduction in
duplication

and
existing
facilities
will

be used to
their
full capacity.



2

A distributed research
infrastructure, ISBE
, is needed urgently for Biology

Systems Biology requires the implementation of a
large
range
of approaches, both
computational and experimental.

What is u
nique
ab
out
modern
Systems Biology
is that all
of
the
approaches are required simultaneously and interactively.

The challenge is how to

integrate the

required
facilities and
expertise
?

An initial answer to this problem has been to create c
entres
which,

at least, h
ave some of the requirements.

Experience

in the US and Europe

has shown
that the most innovative interdisciplinary science is best carried out in settings where
: (a)


4



experimental and computational/theoretical/engineering investigators interact on a daily b
asis
;
(b) where they
build and share open lab
oratories
, resources

and
technology cores
; and (c)
where

the next generation of
Systems Biology
scientists

are educated in the same location
.
However, the evidence is
that in practice systems biologists in
such
centres collaborate more
with groups in other centres than with groups in their own centre.

This is because any specific
Systems B
iology problem requires many
different areas of expertise
-

and

often
this

cannot be
found

at the
right level

within a single
institution
.

It is very difficult to predict w
hich sub
-
disciplines
will be needed two years from now.

Hence,

building topic
-
oriented Institutes
generally
proves to
be

only

a partial solution for most
S
ystems
B
iology
problems
.


The

aim of ISBE
therefore
is
to develop distributed
,

highly interconnected infrastructure using
standardised
methodologies that will support well coordinated
,

multidisciplinary
,

integrated
research in the
fields of
biomedicine
and
biotechnology.

We

are
proposing an arrangement of
Euro
pean
Centres
that will
operate like a systems
infrastructure
-

having
emergent properties and
robustness that will surpass
the simple summation of the
individual
parts (ie a
synergistic relationship).

By
its nature
,

the infrastructure
will assimilate most
of the
existing Systems Biology
activities and facilities,
without altering their
institutional structures.

The infrastructure will also assimilate
expertise
from
other fields.

In
addition, it will
also facilitate
pan
-
European training and education
(inclu
ding cross
-
disciplinary
approaches)
for current and future scientists.

The proposed dynamic
overall infrastructure,
comprising

sub
-
infrastructures
,

will
function

in such

a way that all
of the
expertise required for
any new
Systems Biology
challenge can be
assembled
dynamically.


3

The dynamic
infrastructure
of European Systems Biology

Modern
S
ystems
B
iology projects are not confined to single
institutions
, each
covering
all
of the
research.

Rather,
such projects
need to
connect research groups in various
in
stit
utions
with
specific
expertise and/or
facilities

in order for them
to work

synergistically.

Building on the
experience gained by European research consortia in systems biology, the integrated European
infrastructure will exploit and institutionalise ex
isting synergies and create new opportunities for
efficient research coordination and collaboration. The ISBE will make available cutting
-
edge
technology in experimental and computational systems analysis to the wider community of
European life scientists.

Its backbone will be formed by ~50 centres that specialise in particular

5



experimental and/or computational technologies. These centres will collaborate with a wide
range of scientists on specific projects, train researchers, and act as hubs for further te
chnology
development. A particular challenge in modern biology is the integration of approaches from the
quantitative sciences of physics, mathematics and engineering. The ISBE centres will have a
catalytic role in this process by providing a unique enviro
nment where scientists from all these
disciplines meet, work together and educate each other.

The
European

aircraft
industry
is an example of such working.
The components

of a plane are
built in various factories in different, sometimes remote,
locations a
nd

then brought together in
other factories for assembly.

The infrastructure required for the new
Systems Biology
(see the
figure)
is envisaged as being

similar
in certain aspects:
(i) some of the connected
centres
(
factories’
)

would be small and others la
rger
;

(ii) some connections would lead to
the creation of

research groups
across

centres, (iii) depending on the
type of plane
, different combinations of
factories are involved

-

similarly, different groups would be involved in problems associated with
bio
logical function, cell, tissue, or organisms type;’
(iv) some connections
will be
directed to
repositories of data or models
,

rather than research facilities
;
(v) centres and repositories are
likely to be
hubs connected by ‘superhighways’ carrying
data,
in
formation and
other forms of
scientific
interaction
.

The
Systems Biology
infrastructure
would

host intensive and reciprocal
interactions through its
information
highways

-

for example,
enabling a researcher in one centre
to steer an experiment in another c
entre through a web
-
based computer interface

(this would be
in addition to classical cross
-
laboratory visits
by the scientists involved in the project)
.

The ISBE infrastructure will put the

jigsaw

puzzle of European Systems Biology together.

It will
compri
se

three components
:
(i)
institutions/centres
,

i.e. research facilities at which research
expertise and experimental and
modelling

facilities
exist
,

(ii) repositories of data and models,
and (iii)

broadband connections between components (i) and (ii)
.

The

I
SBE
is envisaged
as an
infrastructure

where

combinations of institutions/
centres will

focus on a different biological
problem
s

by carrying out discovery
-
directed and hypothesis
-
driven research.
These consortia
will focus
on distinct conceptual aspects of b
iology

-

such as model organisms, model cell
populations, diseases, biotechnology, ecology etc. In addition, the development and application
of new technologies will be the main task of a number of the ISBE
partners.

The
combined
expertise and facilities o
f the
ISBE will serve the European Research Area by functioning as
the
entity

for addressing important scientific problems, by disseminating technologies and by
providing open access to data and software. Although ISBE
institutions/centres
will have
comple
mentary activities, each will typically support the following:

de novo

data generation, data
extraction from all pre
-
existing sources, data management and curation, data analysis, model
extraction from literature,
de novo

model generation and validation, v
isuali
s
ation and mode
l
ling,
dynamic interaction of models and data, model driven experimental design, and training.

4

Focus

The
issue
of how narrowly to focus
is so pervasive that it could involve
such a
broad

range of

science

as to

become unmanageable.

Alte
rnately, to

focus on a single disease or
biotechnological challenge would
loose

the advantage
of
much of the expertise that is important
for
Systems Biology
(e.g. quantitative
Metabolomics
, stochastic modelling).

A focus on

6



‘multifactorial disease’
would e
liminate

important applications in white and green biotechnology
and ecology.

Therefore, it is proposed that the focus of ISBE
should
be the integration of
components, from molecules to organisms, towards a complete understanding of those living
organisms

-

including the human, within the context of dynamic interactions with the
environment.


5

The different branches of the ISBE:

TAP, i.e. Tools, Activities & People

H
ere
the different

categories of components of the European Infrastructure
which are
necessar
y
to
accelerate
Systems Biology
are described
.

This is done
by naming an issue and then
describing

some examples
identifying

the required expertise and activities.
It should be noted
that this is only tentative
list (a

more
comprehensive
list
will
be
produ
ced

in the preparatory start
-
up phase of ISBE, and
will
remain dynamic thereafter
)
.

5.1

Tools

5.1.1

Connecting to model generation methodologies

Text mining for experimental data to populate families of parameters values.

High capacity
literature mining for existi
ng models; both mathematical and conceptual.

Link with the
Bioinformatics EIS.

Reverse

and forward
modelling
, of various aspects of
Systems Biology
(molecular level, cell level, intercellular level, organisms level, multiscale in terms of space,
multiscale

in terms of time, multiscale in terms of chemistry, multiscale in terms of biological
hierarchy [transcription, translation, metabolism, function]).

Stability analysis, control analysis,
regulation analysis, differential equation
modelling
, Bayesian
model
ling
, Boolean
modelling
,
cellular automata, differential equations solvers, modularization, flux balance analysis, high
-
throughput parallel computing, stochastic
modelling
, etc., etc.

5.1.2

Connecting to experimental design methodologies

Model and parameter iden
tification, mapping of experimental possibilities onto model
s
, statistics,
model comparison, hypothesis formulation, test design, development of new tools, robot scientist
implementation, search for the required experimental facilities in the ISBE network.

5.1.3

Connecting to component
-
data generation methodologies

The d
evelopment

of a major
experimental infrastructure for component
-
data generation: High
throughput genomics and
Transcriptomics

(DNA array systems, highly parallel DNA
spectrometers

and advanced mul
tiplexing technologies). Equipment relevant to Advanced Mass
Spectroscopy and multiplex systems (array based) for analytical and quantitative proteomics and
the identification of protein networks and assemblages,

5.1.4

Connecting to technology development

Syste
ms

Biology
research program
mes

invariably
have been held back by limitations in
methodologies.

Examples include
:

low rates of DNA sequencing
(
initially
)
, lack of reproducibility
of cultivation and sampling, inability to measure the concentrations of protei
ns and metabolites
accurately, inability to identify new metabolites rapidly in biological samples

etc.

New

7



technologies are being developed
. The
ISBE will connect demand with technology development,
creating both a demand pull and a technology push to dri
ve European Systems Biology.

5.1.5

Connecting to physiological expertise

For Systems Biology, not only
is
data generation a key issue, but
,

also
,

the performance of
functional experiments
involving

the organism or cell type of choice, under
standardised
conditi
ons relevant for model testing.

This requires
: (a)

expertise in batch cultures, tissue culture,
fed
-
batch, chemostat, turbidostat, auxostat, retentostat,
in vivo

cultures (e.g.
tumour

cells
injected into mice
), (b)

rapid
and reproducible sampling
, and (c)

the shipment
of samples to the
data collection
centres
(
see
above).

These will require the functional integration of ISBE to
Biobanking, Clinical Research and Translational Research
centres
across Europe.

We envisage
functional interaction with the BBMRI,
ECRIN and EATRI
S ESFRI projects, respectively.

5.1.6

Connecting to data and software management facilities

Methodologies and expertise for high capacity computing infrastructure, for open access storage
and management of large data sets and databases (petabyte l
evel). We
envisage

collaboration
with the ELIXIR ESFRI project.

Maintenance and distribution of core software (tools) in Systems
Biology. Connection to large
-
scale computing facilities. Collaboration with the EU infrastructure
DEISA, and future HPC ESFRI,
should be
considered.

5.1.7

Connecting to data analysis and data management methodologies

The provision of m
ainstream and
specialised

computers to allow high performance computing in
order to
analyse
and
visualise

biological data, to model protein and multi
-

pro
tein assemblies
(nano
-
machines) and to simulate pathways, networks, cells , tissues and organs. Furthermore,
ISBE Institutes will develop and implement GRID computing systems for massive
ly

parallel
processing
,

integration

with
modelling
,

and

m
odel
-
driven d
ata management.

5.2

Activities

5.2.1

Real
-
time, cross
-
laboratory

data generation

This

component

should enable cross laboratory experimentation, by short research visits
,

as
well as by web
based
cross
-
lab
oratory

experiment
s
. Equipment relevant to Advanced Mass
Spect
roscopy and multiplex systems (array based) for analytical and quantitative proteomics and
the identification of protein networks and assemblages. Gas Chromatography (GC), Liquid
Chromatography (LG), Capillary electrophoresis (CE) as well as NMR and Fourie
r
-
transform ion
cyclotron resonance mass spectrometry (FT
-
ICR
-
MS) for
Metabolomics

and fluxomics
.
Advanced high throughput imaging systems including microscopy, flow
Cytometry

and
automated cell analysis should also be included, to yield essential function
al data. The
infrastructure should incorporate advanced robotic systems for remotely controlled experimental
stations.

5.2.2

Real
-
time, cross
-
laboratory

modelling

Conversely, this
component
should allow experimental systems biologists to involve
modellers

in
th
eir day
-
to
-
day experimental work, again by short research visits
-

as well
as

through web
-

8



based

cross
-
lab
oratory

modelling

facilities. Workflows must permit to link data
-
resources, of
experimental measurements, models and ontologies,
modelling

tools and si
mulation
environments. Multi
-
scale, multi
-
approach models, such as detailed whole
-
cell models or large
physiological reconstructions, should be developed in a modular fashion



taking advantage of
each
site's particular expertises. Generic models must
be d
erived

in specific instances using
remote data for parameteri
s
ation, paving the way to personali
s
ed model
l
ing.

5.2.3

Real
-
time, cross
-
laboratory model validation

The provision of f
acilities for data and model import work flows, with subsequent model
validation.

In Systems Biology this

is a major issue, as there are usually multiple ways
of
designing

experiments
to
validate models (e.g. by parameter fitting).

These multiple ways should
be documented.

Model validation in
Systems Biology
therefore becomes a
determin
ant

of the
extent
to which a multitude of models for a certain system/issue are validated by a number of
data sets that are in existence
.

(The data sets

may themselves have different qualities.
)

Again
,

cross laboratory activities are proposed
.

On

a day
-
to
-
day basis, a model developer

may call
upon

expert groups in model validation design, as well as
the
experimental group carrying out
the validation

-

all in different European laboratories.

5.2.4

Real
-
time, cross
-
laboratory data integration & curation and model
integration & curation

Many data sets and model
s

will become of great importance to Systems Biology.

Hence
,

they
will
need to be
carefully
curated
and documented
.

This activity will set up ‘Jamborees’ for such
curation (
for
example
to enable
the Jamborees
to come to consensus

regarding
, genome
-
wide
maps of yeast and human metabolism).

5.2.5

Dynamic
standardisation

The
standard
i
sation
of experimentation and mode
l
ling

is

crucial for the rapid development of
Systems Biology.

Standards are

i
ndispensable for data inte
gration
and

have to follow the
evolution of techniques and knowledge. Therefore, standards should be adaptable and
incorporate mechanism
s

by which they
can be

changed.
S
tandards,
(
whether reporting
guidelines, data formats or ontologies, but
,

also
,

standar
d analysis tools
)
,
should

only
be
adopted if
the
software allow
s

easy implementation

(
eg
libSBML, cytoscape, bioconductor).

The
c
ontinuous maintenance of standards and their support at a professional level is needed.

5.3

People

5.3.1

Personnel Training and Educatio
n

Biology and Medicine have been transformed by the advent of Systems Biology.
However
,
industry and academia have great difficult
y

in
identifying
on the one hand
life scientists with
cap
ability
in large scale data collection, model
l
ing and data analysis,
and
on the other
engineers/physical scientists with
an
appreciation for the detail and the importance of
the
complexity of biological function.

Most of the ISBE
institutions/centres
will
have
scientists with
diverse expertise ranging from mathematicians, p
hysicists, engineers and computer scientists to
biologists and medical doctors.

Each will be involved in training and educating scientists in
Systems Biology by providing both the necessary scientific personnel and infrastructures
.

More

9



European training
c
entres
dedicated to specific aspects of Systems Biology will be developed
and connected by
the
ISBE.

The training infrastructure will connect training facilities
,

such as
universities
,

throughout Europe, including those in areas where there is more trainin
g in theory,
to areas where training focuses on experiment
s
.

Training will be at all levels, from
undergraduate through MSc, PhD and postdoctoral training, to retraining of industrial and
academic staff.

Regular courses
will take place
at universities, but

there will
also
be
summer
schools, rotation projects, and distance e
-
learning will be part of the overall package.

These will
facilitate discipline hopping
,

as well as cross
-
discipline sabbaticals.

An important issue is that part of the training will have

to be done in non
-
traditional ways,
emphasising
collaboration and integration of model
l
ing and experimentation.

This

will create

a

critical training mass in Systems Biology
. The
ISBE will solve the problem that present
-
day
students have

in relation to con
servative curriculums in

the traditional disciplines.

5.3.2

Methodology and iterative calibration on what is needed for Europe

E
xperience with the
(
otherwise highly successful
)
biological sciences has
shown
that
they
have
not been
optimally
tuned to the needs of

European
Society
, nor have they been targeted
at
addressing
current
biological problems, which require Systems approaches.

With the advent of
Systems Biology
,

the situation has
dramatically
improved.

From now on

it should be possible to
prevent
, such lack

of information flow between science and society.

The
ISBE should
,

therefore
,

house units that
analyse
the scientific methodology used (philosophy of science) and address
the information flow between European Systems Biology, policy makers, and the Europea
n
public (Public Health Management, ethics, well
-
tuned information about progress, information
back from public and politicians).

5.3.3

Meetings

ISBE will coordinate Systems Biology conferences targeting development and applications.

5.3.4

Work
-
workshops and jamborees

The
ISBE will
organise
workshops during which experimentalists and model
l
ers

meet

for a
number of days
,

with the assignment of producing a model of a
defined

biological process.

A
regular

s
eries of such work
-
workshops
(
or ‘jamborees’
)

will enable
the
upda
ting of model
s

with
advancing knowledge.

5.3.5

Platforms linking with industry

The
ISBE will install platforms where scientists from its

constituent

institutions
and scientists
from industry and public health institutes
can
meet on a regular basis to discuss

top
ics of mutual
interest
.

This should enable
the
optimal steering of
the
ESBI towards public and industrial utility.

The
se

activities will
also
connect to those
involved in
the Innovative Medicines Initiative (IMI).

5.3.6

Embassies

The
ISBE will have ‘embassies’ t
o help
connection
to the outside world, such a
s

Systems
Biology infrastructures outside Europe.

The
ISBE will actively stimulate the
organisation
of
similar infrastructures in other parts of the world, in part through its S
cientific
A
dvisory
B
oard
.


10



The
ISB
E will foster close links with the other life science ESFRIs (e.g. BBMRI, ELIXIR,
INSTRUCT) and EU networks of excellence such as

BioSim and ENFIN (and successors).

6

Management

The ISBE will be
a

new
phenomenon for
the Life Sciences
because

of its scale and

complexity.

It will require strong management, unprecedented in Biology, and perhaps only comparable to
that of CERN.

The
aim is that the
management structure
will

crystallise
in the set
-
up period of
ISBE.

It is recommended that a strong
,

yet responsive
,

individual

lead the first phase, assisted
by a secretariat and a steering committee
-

representing the components of the infrastructure,
the funding bodies and the public.

The Steering Committee will
organise
calls for and
subsequent evaluations of, propos
als for additions to the infrastructure.

A Scientific Advisory
Board (e.g. such as one consisting of Lee Hood, Hiroaki Kitano, Bernard Pallson, Douglas
Lauffenburger, Sang Yup Lee, chaired by Sydney Brenner
)

will be asked to check on the
excellence of ISBE
.

The
ISBE will be managed at various levels.

These include the level of the
institutions,
but
,

also
,

at the
overarching level.

A CERN model may be used in the beginning, but may need to evolve
to manage
a
structure that is more suitable for Systems Biolog
y.

Early in the preparatory phase
of ISBE, memoranda of understanding between the components
institutions
will be put in place.

Standards
and IP issues will
then
be settled.

7

Timing

It is proposed that ISBE begins as a preliminary
infrastructure
in a prepar
atory phase.

During
these three years it
will grow

into a full blown infrastructure.