The 2017 Nobel Prize in Physiology or Medicine was awarded to
Dr. Jeffrey Hall, Dr. Michael Young, and Dr. Michael Rosbash for their discovery of
the molecular mechanisms controlling circadian rhythms!
Because I'm not on the Nobel Prize selection committee, I can't
tell you why they picked this discovery over a number of other deserving discoveries
but I can tell you what these researchers did to win their prize and why it is
definitely worth the Nobel!
Every morning you wake up and go throughout your day.
You eat, you work, you get sleepy, and
you go to bed only to wake up the next day and do it all over again!
And you aren't alone in this behavior.
Every animal and plant you've ever seen does the exact same thing!
Every living creature on this planet is on a 24-hour cycle of activity and rest called the circadian rhythm.
What's amazing is that we do this even in complete darkness.
So how do we know when it's day and when it's night without the Sun?
Our three Nobel Prize winners had the same question, and
to answer it they used a very simple and unassuming insect...
the fruit fly.
These scientists worked on a gene called period that influenced the
circadian rhythm of the fruit fly. One mutation shifted the cycle from the
normal 24 hours to a shorter 19, and another one to a longer 29.
A final mutation removed all rhythm from the fly causing it to wake and rest at seemingly
random times. But what was this gene doing?
Was it making a protein that controls the timing?
And if so what was that protein doing?
and where was this protein in the fly?
or even in individual cells of the fly?
and finally how did it change the circadian rhythm?
In 1988, a few of those questions were answered.
A new paper came out that revealed that the period protein is in the nucleus of
cells scattered throughout the body of the fly and that period was found more
during the night with very little around during the day.
This was the first hint that period was cycling in the same way that day and night do!
From this protein cycling discovery, they came up with the idea that perhaps
the period protein turned off its own gene.
One of the easiest ways to turn on and off a gene is
to have the protein that gene makes also be the switch master.
The researchers thought that the period protein turned off its own production, which
would lead to a cycle of period amounts.
It's kind of like when your car shuts down because it overheated.
Once it cools down you can start it up again, but
when the engine gets too hot it'll shut off.
Over the next six years, period was heavily studied to find evidence for this feedback loop
And in 1994, another player showed up that helped
confirm the feedback loop was real! Another gene called Timeless.
The timeless protein worked with period to move into the
nucleus of cells and stop more period from being made.
Timeless is kind of like an employee with security clearance taking
in an expert. Without timeless, period can't get into the nucleus.
But period and timeless aren't enough to explain the whole cycle.
The final piece of the puzzle came in 1998 with
another gene called doubletime. The doubletime protein reduces
the stability of period outside of the nucleus which leads to a delay in the cycling.
So the whole setup goes something like this:
The period gene starts making the period protein.
The doubletime protein limits the stability of period so it doesn't build up too quickly.
Timeless shows up and starts teaming up with period to
move into the nucleus, and period shuts down its own production.
But once the amount of period in the cell gets too low...
The whole process starts up again!
A calm, cool, and collected 24 hour cycle.
After the discovery of doubletime, the molecular basis of the
circadian rhythm was well in hand.
Scientists are still working out other rhythm details and how
the circadian rhythm affects the rest of your body, but
thanks to Dr. Hall, Dr. Rosbash, and Dr. Young the
molecular basis was no longer a mystery.
But to really understand part of what made their work so special,
you have to understand the time that they did it in.
DNA was discovered in 1953, but it wasn't
until 1966, 13 years later, that we really understood what all of those
A's, G's, T's, and C's were actually for. They were
coding for the individual amino acids found in proteins.
The 70's brought the first animal gene ever cloned and the
ability to actually sequence DNA. And it wasn't until 1983 that we found a way to
be able to make more DNA really quickly using polymerase chain reaction or PCR for short.
Molecular biology was progressing but it was still massively
difficult to go from a physical behavior to finding out
exactly which genes were responsible for it.
Let alone for a complicated behavior like circadian rhythms.
The fact the molecular basis of circadian rhythm was found in the
80's and 90's is incredible!
Circadian rhythms control so much of our health that we can
feel them get out of wack every time we hop on a plane and change time zones!
The work these Nobel laureates did is beautiful.
It's a great feedback loop that perfectly mimics our days and
nights here on earth. And the fact that they found the molecular basis for this
at a time where molecular biology and
genetic techniques were only just getting their start, only makes the work
that much more impressive!
So congratulations to the 2017 Nobel Prize in Physiology or Medicine winners!
And I only have one final question...
can you cure my jet lag yet?
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out new videos every other Friday.
And a special congratulations to Dr. Michael Young who
won this prize at my home institution of Rockefeller University.
It's always great to see someone so nice win such an honor.
So keep up the great work Mike!
And I'll see you all next time.