Hello, I'm Tom Pollard from Yale University,
Department of Molecular, Cellular and Developmental Biology.
Today I'm going to discuss how complimentary approaches are
used to understand molecular mechanisms of cellular processes.
This strategy is called the reductionist strategy.
It starts off by defining a biological question which can come from
clinical medicine or natural history or observations of cells and other organisms.
Once a good biological question is defined.
Then the next question is finding an inventory of parts,
some molecules that operate the system of interest.
Then there are three major types of research that needs to be done
to understand how these parts are used in the biological process.
One is the structural agenda that involves light and electron microscopy,
X-ray crystallography, nuclear magnetic resonance spectroscopy,
and molecular dynamics simulations.
Secondly, there is a bio-chemical agenda.
This is used to establish interactions among the molecules and to
measure the rate constants and equilibrium constants for the reactions.
This research results in hypothesis yet to be
formulated into mathematical models and tested by computer simulations.
Third part of the agenda deals with cells. One needs
to measure the concentrations of the molecules of interest in cells,
document their dynamics in live cells.
Then what one does is take
one's biochemical ideas from the chemical part of this work and
test whether simulations of
these biochemical hypotheses can reproduce and predict cellular behavior,
both in normal cells and perturbed cells.
Usually at this point, the process fails because the models aren't good enough.
One wants to go back and look to see whether parts are missing,
whether the biochemical measurements are good enough.
Then cycle back to the cells to see whether
the mathematical models can reproduce the behavior in the cells.
So on circles around the right-hand side of this diagram,
getting closer and closer to understanding the underlying mechanism.
This approach requires facile genetic editing in
order to make cells that can be used to test the hypotheses.
So we'll come back to how to edit genes later in the talk.