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0:00
This is Frank Doyle.
I'm a faculty member in the
Department of Chemical Engineering
at University of
California Santa Barbara.
And I'll be giving a lecture
on controlled feedback
and cellular responses.
0:12
I want to start by walking
through the origins of this field
of systems biology and showing
you some profound connections
with the field of controls.
If one goes back perhaps
a century and a half ago,
you find the work of Claude Bernard,
who was a French physiologist,
was the first to coin the
term milieu interieur,
which we now understand
as homeostasis.
Walter Cannon was the first to
really introduce that English term,
homeostasis, as the ability
of the body to maintain
normal, coordinated, physiologic
processes despite disturbances
and interruptions to that system.
And the last individual here
to really play into that field
is Norbert Wiener,
who's a giant figure
in the field of control
and communications.
And he coined this expression, or
this term, cybernetics as a way
to envelop all of
communications and control,
whether it's a natural
or a synthetic system.
1:11
Here, I'm showing two
different circuits
that come from the natural world.
On the left is the gene
regulatory map for a sea urchin.
That comes from Eric Davidson's lab.
It's probably the most
complex gene network
that's been put together
for a particular cell type.
And on the right hand side we have
an engineering circuit diagram,
in fact, a rather dated,
antiquated system, a shortwave
radio circuit diagram.
But what's quite common
to both of these diagrams
are the fact that there are
numerous feedback relays.
There's modular architectures.
There's redundancies built in.
And these are common to both
biological networks, as well
as engineered, or
synthetic networks.
And that's why those of us
who live on the engineering
side of dynamics, and
control, and network theory
are bringing new insights and
new opportunities for unraveling
the kind of biological networks
like one sees on the left here.
The properties that we're
looking to understand,
by bringing understanding
from feedback control,
are things like robustness, the
ability of both of these circuits
to maintain high
levels of performance
despite noise, and
perturbations, and uncertainty,
and really, particularly in
biological system, the fact
that we have two types of
noise which are omnipresent.
The first type is
external perturbation.
So if this is a cell,
it might be disturbances
in the surrounding tissue.
If these are molecules
in a cell, it could
be disturbances in the
interior of the cell.
But we also have
intrinsic variability
built into natural
systems, which is the fact
that we have low
numbers, low copy count,
of individual
components in the cell,
so that reactions, or
interactions, between molecules
take place in a
probabilistic manner.
All this together points to the
fact that we have tremendously
variable, tremendously
noisy systems.
And in the circuits on the
left, the biological circuit,
we maintained extraordinary
high levels of performance.
These organisms have
evolved to achieve
these remarkable
levels of performance.
And the price for failure, quite
frankly, in the biological realm,
is death.
So in fact, Mother Nature
has created these paradigms
that we now, as engineers,
are trying to unravel.
