By Ellen Kuwana
Neuroscience for Kids Staff Writer
October 7, 2004
Dr. Richard Axel
Image courtesy of Howard Hughes Medical
Institute |
Dr. Linda Buck
Image courtesy of Fred Hutchinson Cancer Research
Center |
Usually when the phone rings in the wee hours of the morning, it's bad
news. Not so when the Nobel Prize Committee in Sweden makes their
congratulatory phone calls. Researchers Richard
Axel, MD, a professor at Columbia University (New York, NY) and Linda
Buck, PhD, a professor at the Fred Hutchinson Cancer Research Center
(Seattle, WA) each received a wake-up call on October 4, 2004. Their
groundbreaking research about the genes involved in the sense of smell
-- and how that information is transmitted to and translated in the brain
-- is being honored with the 2004 Nobel Prize in
Physiology or Medicine. The prestigious award, the highest honor a
scientist can receive, comes with a $1.3 million check that will be split
between Dr. Axel and Dr. Buck.
Axel and Buck tackled an area of research in which little was known
previously: how the sense of smell, or olfaction, works. The
numbers generated from their work speak for themselves. There are more
than 1,000 different genes involved in the sense of smell; this, then, is
the largest gene family known in the human genome. This represents 3% of
the human genome, demonstrating how vital our sense of smell is to our
survival; we need to detect food and discern if it's still edible (not
rotten or poisonous), for example. Most animals use smell to find food,
avoid predators and interpret their environment.
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The two researchers share a common past: Dr. Buck did her
post-doctoral
work in Dr. Axel's lab in the early 1990s. Both researchers are Howard
Hughes Medical Institute investigators, an honor that recognizes their
innovative research with financial support.
The long path to becoming a research neuroscientist:
- K-12 education
- College degree (4 years)
- Graduate school/research for Ph.D. (anywhere from 3-7 years) or
medical school for an M.D. (4 years)
- Post-doctoral work (1-6 years in an established scientist's lab; some
researchers complete one or more "postdocs."
- Job hunt
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The sense of smell results from a complex interplay between the nose and a
part of the brain near the front called the olfactory bulbs. Within the
skin (epithelium) inside the nose - are you sitting down? - are up to
12 million olfactory receptor neurons; each neuron sends
a single dendrite to the epithelium. The dendrite houses 5-20 hair-like
projections, called cilia, that contact the mucus. The cilia contain the
odorant receptors. The other part of the neuron sends a single axon through the bony plate above the nasal cavity to the
olfactory bulb.
Once an odor is detected, an electrical signal travels along the neuron
straight to the olfactory bulb in the brain. From the olfactory bulb,
which is like the switchboard for smell information in the brain, the
information is routed to other parts of the brain, including limbic areas. The sense of smell, therefore, is
linked strongly to memories and emotion. By using chemicals in the lab to
trace the pathways involved in smell, the researchers have been able to
map how certain smells trigger the olfactory receptors, and how the
information is conveyed by neuronal signals to the olfactory bulb and on
to other parts of the brain.
Drs.
Buck and Axel tackled a two-part question about smell:
- How do
mammals detect so many different chemicals as having smell?
- How does
the brain translate information (about smell) into perceptions?
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Buck chose a novel approach to solve the mystery of how the nose-brain
system recognizes the thousands of odor molecules (called "odorants")
floating around us in the world. The question was: Did many very specific
receptors detect the odorants, or only a few receptors, working overtime?
The approach was: Search for the genes encoding receptors found only in
the nose, instead of searching for the receptors themselves. Buck's former
mentor, Axel, called this approach "an extremely clever twist."
The research to solve this receptor mystery borrowed clues from other
studies on receptors.
Clue one: Many receptor
proteins have a similar structure: they
cross the cell membrane seven times, creating a zig-zag shape that
resembles a snake.
Clue two: These proteins often
interact with
another type of protein, G-proteins, to transmit signals to the inside of
the cell.
Clue three: These proteins
often share stretches of DNA in common.
These clues helped Buck to design probes (think of a fishing hook shaped
for a certain fish) to identify these sequences in rodent DNA. The better
you
know what you are fishing for, the better you can design the "hook" to
catch it.
By carefully designing the "hook," or probe, Buck saved years of work.
Once genes had been identified in rodent DNA, a similar approach was used
to fish out the genes in collections of DNA from other species such as
humans, mice, dogs, catfish and salamander.
Buck is expanding her research on odorant receptors to other types
of receptors, such as those involved in bitter tastes, sweet tastes and
pheromones. Pheromones
are chemicals produced by animals to signal to others in their species.
The first pheromone, identified in the 1950s, was an attractant signal for
silkworm moth mating. Research on insects, though, is much easier than on
humans, and the topic of human pheromones is controversial. Don't invest
in that pheromone-enhanced perfume yet. The jury is still out on whether
you can improve your attractiveness by exuding certain chemical signals.
Animals have a vomeronasal organ (VNO) that responds to pheromones, but no
such organ has been pinpointed in humans. Axel has noted that if humans
have one, it's most likely disrupted by plastic surgery in those who have
nose jobs.
Image courtesy of the Nobel
Foundation
| A former student's (Ewen Callaway) recollection on
Linda Buck's
approach to scientific questions: "In my discussion with
her, I was struck by her openness to different solutions to basic problems
in neurobiology. She was willing to embrace a theory different from her
own as long as it was based on careful research and good science. She was
also extremely creative. I had read the literature pretty thoroughly
before I met with her, and still she opened my eyes to a number of ideas
about the molecular biology of smell that had not been explored by other
scientists."
Officials at Columbia University, where Axel has spent his entire research
career, responded to the news of the Nobel Prize with praise for Axel:
"...his research solves the puzzle of how we translate sensations
around
us into knowledge that is key for our survival..."
--Columbia University President Lee Bollinger
"(Their) experiments represent the highest form of creativity,
scientific
discipline and scholarship."
--David Hirsch, executive vice president for research
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Did You Know?
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- Perfume makers claim that they can identify as many as 5,000
different
types of odorants. (Kandel, et al., Principles of Neural Science, 4th Ed.,
page 625).
- Mice have approximately 1,000 odorant receptors encoded by an
estimated 1,500 genes. Humans have around 350 odorant receptors. ( "Mechanisms
Underlying Perception and Aging" from the HHMI)
- Bloodhounds have approximately 4 billion olfactory receptor cells;
humans have approximately 12 million of these cells. (Shier, D., Butler,
J. and Lewis, R. Hole's Human Anatomy & Physiology, Boston: McGraw Hill,
2004.)
- Dr. Linda Buck is the 11th woman to receive a Nobel Prize in sciences
in the 103 years the prizes have been awarded.
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