NOBEL PRIZE IN

MEDICINE 2021
AWARDED FOR
DISCOVERY OF
RECEPTORS FOR
TEMPERATURE & TOUCH
HISTORY
• Born in Brighton Beach, Brooklyn, NY.
• An American physiologist and Nobel
Prize laureate known for his work on
molecular mechanisms of pain
sensation and heat.
• Professor at the University of
California, San Francisco.
David Julius
4th November 1955
EDUCATION

Abraham Lincoln High School University of California, Berkeley

Massachusetts Institute of Columbia University

Technology
 AWARDS & ACHIEVEMENTS
Inauguration Perl- UNC Neuroscience prize -2000
Shaw Prize in life science and medicine -2010
2010 Prince of Asturias prize for Technical Scientific
Research.
Dr. Paul Janssen Award -2014
The Canada Gairdner Foundation International Award and
HFSP Nakasone Award- 2017
 AWARDS & ACHIEVEMENTS
2019 Rosenstiel Basic Medical Sciences Award jointly with
Ardem Patapoutian.
2020 breakthrough prize in life sciences.
2020 Kavli Prize in Neuroscience together with Ardem
Patapoutian.
2020 BBVA Foundation Frontiers of Knowledge Award.
RESEARCH CAREER
 Faculty at the University of California,
San Francisco, 1989.
 Julius’s lab cloned and characterized
TRPV1(1997), TRPM8 (CMR1) and
TRPA1.
 Editor of peer reviewed journal “Annual
Review of Physiology” from 2007-2020.
 Contributions to the study of
nociception by discovering toxins that
modulate these channels.
The long road to Nobel Prize

David Julius Ardem Patapoutian

SCIENTIFIC BACKGROUND
 Temperature and pressure activate different types of
nerves in the skin.
 Research Question: Molecular transducers responsible for
detecting and converting heat, cold and touch into nerve
impulses in the sensory nervous system ???
CONTRIBUTION
 David Julius wished to identify the
cellular target of capsaicin.
 Identified cDNA encoding novel ion
channel TRPV1 belonging to family
of transient receptor potential ion
channels.
 Discovery of TRPM8, a related cold-
sensitive receptor.
 Several other TRP-receptors
identified.
FUNDAMENTAL QUESTION
 What is the nature and molecular identity of the
receptors that can sense temperature and touch.
How can those sensors convert stimuli into action
potentials within the somatosensory nerve fibers ?
SENSING THE ENVIRONMENT
 Somatic senses involve peripheral sensory pathways that
detect and convert objective information about physical
properties of various stimuli into electrical signals that are
conveyed to the central nervous system.
 Different stimuli activate different types of sensory neurons.
THE DISCOVERY OF THERMOSENSITIVE
ION CHANNELS FOR THERMAL SENSATION

www.nobelprize.org/prizes/medicine/2021/press-release
• Sensitivity to elevated temperature and
pronounced activation by heat leading to
cellular Ca2+ influx.
• TRPV1 acts as the capsaicin- and
heat-activated ion channel.
• Role as a transducer of noxious heat;
great reporter for pungency.
 www.nobelprize.org/prizes/medicine/2021/press-release

TRPV1 - non-selective cation channel; when activated

by capsaicin, sodium and calcium ions flow through
TRPV1 into the cell to depolarize nociceptive neurons,
leading to action potential firing and finally the
sensation of spiciness.
THE SENSATION OF
NOXIOUS HEAT
 TRPM3 - second sensor for
noxious heat in Trpv1
knockout mice.
 TRPA1- transducer for
pungent chemicals.
 THE SENSATION OF COLD
 Non-noxious cold sensation in
humans and mice starts around
28°C, remarkable precision
detecting changes as small as
0.5°C in skin temperature.
 Menthol elicits sensation of
innocuous coolness in humans.
 Identified TRPM8(cold sensor)
activated by low temperature.
www.nobelprize.org/prizes/medicine/2021/press-release
 HISTORY
• Armenian-American molecular
biologist, neuroscientist, and Nobel
Prize laureate was born in Beirut,
Lebanon.
• Known for his work in characterizing
the PIEZO1, PIEZO2, TRPM8 receptors.
• Neuroscience professor, Howard
Hughes Medical Institute investigator
at Scripps Research in La Jolla,
California. Ardem Patapoutian
2nd October 1967
American University of Beirut University of California, LA
EDUCATION

Caltech University UCSF

 AWARDS & ACHIEVEMENTS
• Position at Genomics Institute of The • Recipient of the Lewis S.
Novartis Research Foundation (2000- Rosenstiel Award (2019; with
2014). Julius)
• Young Investigator Award for • The Kavli Prize in
Neuroscience (2006). Neuroscience (2020; with
• Investigator of the Howard Hughes Julius).
Medical Institute (2014).
• Fellow of the American Association for
the Advancement of Science (2016),
member of the U.S.National Academy of
Sciences (2017).
 RESEARCH CAREER
• Biological receptors for temperature and
touch (nociception), signal transduction of
sensors.
• Discovered channel for sense of touch
PIEZO1 and PIEZO2.
• Significant contributions to the
identification of novel ion channels and
receptors.
• Recent work uses functional genomics
techniques to identify and characterize
mechanosensitive ion channels.
CONTRIBUTION
 Patapoutian identified two mechanically-activated
ion channels, PIEZO1 and PIEZO2, represent novel
class of ion channels functioning as mechanical
sensors.
 Demonstrated that PIEZO2- major mechanical
transducer in somatic nerves required for our
perception of touch and proprioception.
Noble lecture

‘How do you feel? The

molecules that sense touch’
OUR PERCEPTION OF REALITY
IS DEFINED BY OUR SENSES
 Olfaction : chemical
 Taste: chemical
 Vision: photon
 Hearing: mechanical
 Touch/pain : mechanical,
thermal, chemical
OUR SENSE OF TOUCH IS
AMAZING
 Human tactile
discrimination
extends into the
nanoscale;
indentation sense 500
times thinner than a
human hair.
MECHANOSENSORY NEURON
 Neurons responsible for
detecting
mechanosensory stimuli
relevant for touch,
proprioception, pain
which resides mainly in
DRGs.
 TRP ion channels in
thermosensation
 How big is an ion
channel?
MECHANICALLY ACTIVATED
(MA) ION CHANNELS
 Why has it taken
too long to
identify this
elusive
mechanosensory?
 PIEZO
 Very large molecules
 PEIZO1 & PEIZO2
 PIEZO in Plasma Membrane
 Sits in plasma
membrane. Any
tension in membrane
will cause flattening
of PEIZO structures ,
hence activation.
 PEIZO2 robustly
expressed in DRGs.
IS PIEZO REQUIRED FOR
PROPRIOCEPTION?
HOW ABOUT PAIN,
“TACTILE ALLODYNIA”
ROLE OF PIEZO IN
INTEROCEPTION
 Respiration
 Breathing
 Urination
ROLE OF PIEZO1 BEYOND
SENSORY NEUROBIOLOGY
PIEZO1 REGULATES RBC
VOLUME
GOF : Dehydrated RBCs
LOF : Overhydrated
RBCs

Overall hypothesis????

GOF PIEZO1 provides

protection against
malaria infection in
mice.
CONSEQUENCES OF
GOF PIEZO1
PIEZO IN PLANTS
WHAT ARDEM CONCLUDED?
 PEIZO2 - principal mechanosensory for touch,
proprioception, many interoceptive functions.
 PEIZO1 - predominant role in non neuronal cells.
 Studies of human and mouse genetics provide
foothold into unexpected roles of
mechanosensation in physiology and disease.