Biology Reference
In-Depth Information
of the life cycle.
9
When observed under time-lapse photography, the aggregation process is
not a simple movement of individual cells radially towards one central point. Instead, cells
form connected, pulsing streams that spiral in towards the centre (
Figure 25.3
c).
When the internal cell biology of the chemotaxis system of the amoebae (described in
Chapter 9) had been identified, it raised the question of whether the complex spiralling
streams emerge from the interaction of many cells running their basic chemotaxis-and-relay
system or whether some extra mechanism was required to explain it. Computer models
that include a pacemaker cell, the cAMP chemotaxis-and-relay system but no other signalling
systems do predict the formation of streams and, if cell density is high enough, of spirals.
10
It
would have been logically very difficult to prove that no additional signalling systems were
necessary for the formation of spiral streams by wet-lab research alone. Modelling, either in
a computer as was actually done or, in principle, by building the cAMP chemotaxis-and-relay
system into other cells in a synthetic biology approach (Chapter 27), provides a clear test of the
hypothesis that this system alone is sufficient for the high-level behaviour to emerge.
Exploratory Modelling
One form of exploratory modelling is testing the implications of hypothetical mechanisms
(rather than their feasibility), and exploring the effects of altering parameters of the simula-
tion. A recent example of this approach
11
is provided by a computer simulation of pancreatic
cells in a three-dimensional space that is provided with other 'tissues', such as the notochord
and aorta, which are a source of diffusible signalling molecules (FGF2 and activin from the
notochord, FGF10 and BMP4 from the aorta), the production of these molecules being
different at different times. The cells are modelled to have responses to different concentra-
tions of these molecules; these responses include differentiation and proliferation. Running
the model with different production of soluble factors generates a range of results, some
reminiscent of a real pancreas and others of different types of aberrant morphology. Changes
in location of the notochord or aorta can also be modelled, and these produce aberrant
morphologies too. Some of these have been verified against in vivo knockouts, suggesting
that the model works. Having such a model allows researchers to explore the effects of
altering other parameters
12
and, in particular, to make subtle changes to identify which mol-
ecules are real regulators of morphogenesis and which are simply necessary
13
(the difference
between necessity and regulation will be discussed further in Chapter 28).
The great value of this type of exploratory modelling is that it can produce surprising,
counter-intuitive results that can be tested back at the bench. An example of this type of study
is provided in Chapter 26, which describes a model of cell colony spreading with or without
contact inhibition of locomotion. The model shows that efficient invasive growth of a colony
depends on inhibition of locomotion
d
quite the opposite of what most people would intui-
tively guess and quite the opposite of what a generation of cancer researchers assumed.
The other form of exploratory modelling is the use of a computer as a cheap sandpit in
which to explore many possible ways of 'wiring' regulatory systems and morphogenetic
effectors to see which arrangements produce interesting morphogenetic behaviour. Depend-
ing on context, 'interesting' could mean representative of a real morphogenetic event in
a naturally evolved organism or it could mean representative of a desired event in a tissue
engineering project. It could even mean a morphogenetic event that seems never actually
