After 4 years spent at EPFL (Ecole Polytechnique Fédérale de Lausanne) for my PhD thesis in the lab of Félix Naef, I was eager to finally spend some time on …
Day
Night
Day
Night
Day
Night
Nature lives by the rhythm of this alternation between day and night.
The environment changes, as do the activities of life.
One example, for the most simple organisms such as bacteria,
it is crucial to protect their DNA from ultraviolet rays
during the daylight hours.
The nighttime is the safest time for them to replicate.
As you can find all around you,
evolution and speciation has created a multitude of
plants, animals and other organisms.
Certain functions that have appeared during the course of evolution
are useful and are therefore conserved in future generations.
Besides the visible functions,
there are loads of simple molecular mechanisms
that have been conserved during evolution.
One of these examples is the circadian clock.
Indeed, having an internal clock is a very practical way
to enable anticipation of environmental changes.
Practically all living species possess a circadian clock.
As for humans, we can feel the force of this clock
when we travel long distances and must take a certain amount of time
to re-synchronize to our new environment.
In my thesis, I was interested in the mammalian circadian clock.
In particular that of mice.
And to be more precise, I worked on the clock in mouse liver.
Indeed, the clock in the liver is not exactly similar
to that in the heart or in the kidneys.
Look and see a bit more clearly the details of this clock…
In each cell of our body, one find the genetic network
that makes the core of the circadian clock.
A dozen genes interact to form the core of the this clock.
They then provoke the rhythmic expression, during the 24 hour period,
of an ensemble of other genes.
But what does it mean for a gene to be expressed rhythmically?
Genes, located on DNA, code for proteins.
The expression of a gene into a protein is done is two principal steps:
First, the gene is transcribed into a messenger RNA.
Second, this messager RNA is translated into a protein.
These proteins go forth to perform various tasks in cells.
In the context of the circadian clock, the rhythmic expression of genes therefore means that the gene is transformed into a protein at certain moments of the day but not at others.
This process of expression is tightly regulated.
Indeed, each gene must be expressed exactly at the right moment
At this time, the scientific community doesn't know exactly how each gene is regulated in order to be expressed at exactly the right moment.
The moment of maximal expression depends on a number of factors.
In particular, it depends on the rate of production
and on the rate of degradation.
We can now measure with some accuracy the time at which the production of the RNA is maximal.
For example, one can measure the amount of polymerase II found on each gene.
Polymerase II is the molecular machine that transcribes gene.
On the other hand, it is more difficult to measure when the degradation
is maximal because there is no unique mechanism of degradation.
One must therefore use the principle of deduction.
For example, take two genes and measure their rate of synthesis and their rate of accumulation.
The first gene is highly synthesized but accumulates slowly.
This indicates that degradation is significant.
The second gene is weakly synthesized but accumulates quickly.
This indicates that degradation is very slow.
Therefore, without measuring the rate of degradation,
but having an idea of how much is produced and how much accumulates,
one can estimate the rate of degradation.
Thus, during my thesis, I applied this reasoning to the particular case
of genes that are expressed in a rhythmic manner.
I could therefore detect the genes for which degradation
is dynamic and changes during the course of the day.
It turns out that one observes very few genes expressed in a constant manner and then degraded rhythmically.
Generally, if a messenger RNA is rhythmic, this is because the gene is produced rhythmically.
Nevertheless, there are some examples of messager RNA for which production is amplified or adjusted, as a function of time, with the help of degradation.
What are the general conclusions?
Finally, and a good thing, the cell is not wasteful:
it doesn't consistently produce too much in order to
waste energy degrading the extra. Bravo cell!
it doesn't consistently produce too much in order to
waste energy degrading the extra. Bravo cell!
Finally, something I didn't mention until now,
that before me, other researchers in other labs
also worked on the same topic.
And we are not really in agreement…
A large part of this difference comes from the measurement technique.
But also from the method for prediction degradation.
Since I am an engineer and I spent some time learning many equations,
it was pretty logical to apply a bit of this knowledge to questions of biology.
The use of a mathematical model to describe biological phenomenae
played a major role in the conclusions that have been drawn.
But rest assured, if this subject is really important for biology,
other labs are looking to determine the importance of rhythmic degradation
And do you think there will be a Nobel?
I don't know…

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