Awarded to: Two US based scientists David Julius at the University of California, San Francisco, and Ardem Patapoutian at Scripps Research, La Jolla, California,
Contribution: for discoveries on receptors for temperature & touch (together called as somatosensation)
Experiment of David Julius: Discovery of TRPV1 receptor for temperature and pain
Worked
on how the
chemical compound capsaicin causes the burning sensation we feel when we come
into contact with chili peppers? Is there a single capsaicin receptor?
Experiment
of David Julius Step
by step explanation
1. First created a cDNA
library by activating rodent dorsal root ganglia sensory neurons with capsaicin.
2. Expressed genes mRNA
is isolated and used to prepare cDNA library. These genes were thought to react
to pain, heat, and touch or causing that burning sensation
Hypothesis
Julius and colleagues
hypothesized that the library would include a DNA fragment encoding the protein
capable of reacting to capsaicin.
3. They used capsaicin
insensitive cell line to find out this gene reacting to capsaicin if present.
4. A single gene was
identified that was able to make cells capsaicin sensitive. This is ‘gain of
function experiment’ where the introduced or transfected gene gives the cell
with the ability to respond to capsaicin.
5. Further studies revealed
that the identified gene encoded a novel ion channel protein and this newly
discovered capsaicin receptor was later named TRPV1.
The significance of TRPV1 discovery
On the basis of this
discovery, many additional temperature-sensing receptors were identified
TRPM8, a receptor that
was shown to be activated by cold. Additional ion channels related to TRPV1 and
TRPM8 were identified and found to be activated by a range of different
temperatures.
Many TRPV receptors
were identified responding to changes in temperature.
Experiment of Ardem Patapoutian: Discovered PIEZO2 as a mechanosensitive ion channel for touch and proprioception* (*the sense of our body’s movement and position in space)
Experiment
of Ardem Patapoutian
Step by step explanation
1. First identified a pressure
sensitive cell line called Neuro2A that gave off a measurable electric signal
when individual cells were poked with a micropipette.
2. Identified 72 genes
by expression studies on this cell line after inducing pressure by poking with
a micropipette.
Hypothesis
One of the 72 genes
might be responsible for responding to mechanical stimuli
3. Each gene, from 1 to
72 silenced by RNA interference one at a time and assessed electric signal
generated. He received electric signal from gene 1 to 71 suggesting that that
genes are not involved. This is ‘loss of function’ experiment
4. When silenced the
candidate gene 72, no electric signal was generated suggesting that gene 72 is
responsible for pressure sensitiveness or mechanosensation
Further studies revealed
a new and entirely unknown
mechanosensitive ion channel and was given the name Piezo1, after the Greek
word for pressure (í; píesi). Later a second gene was discovered and named
Piezo2. Sensory neurons were found to express high levels of Piezo2 and further
studies firmly established that Piezo1 and Piezo2 are ion channels that are
directly activated by the exertion of pressure on cell membranes. In further
work, Piezo1 and Piezo2 channels have been shown to regulate additional
important physiological processes including blood pressure, respiration and
urinary bladder control.
Importance of this work
Explained
how heat, cold and mechanical force are sensed and transformed into nervous
impulses that enable us to perceive and adapt to the world around us.
