In this issue: 2013 Donor Honor Roll

Where cures begin.

Salk Institute 01| 14				January 2014
Inside Salk

William R. Brody, M.D., Ph.D.
President
Marsha A. Chandler, Ph.D.
Executive Vice President
Rebecca Newman
Vice President,
External Relations
Anna-Marie Rooney
Chief Communications Officer
Christopher Emery
Director of Scientific Communications
and Media Relations
Sarah Lifton
Copy Editor
Rhiannon Bruni
Kelly Chi
Scott Edwards
Renee Twombly
Sarah Williams
Diane Wilson
Contributing Writers

1030

One on one with…Jan Karlseder

Next generation: Kevin Curran

3 EXECUTIVE MESSAGED I S C O V E RY R O U N D U P

23 Salk scientists add new bond to protein toolbox

L E A D S T O RY

4 The science of healthy aging

24 Unique epigenomic code identified during humanbrain development		

INSTITUTE NEWS25 Insulin plays a role in mediating worms’ perceptions

10 One on one with…Jan Karlsederand behaviors

26 High-resolution mapping technique uncovers

14 Symphony at Salk
15 Salk celebrates Irwin Jacobs’s 80 birthdaythSalk earns third consecutive Charity Navigator
four-star rating

16 Inaugural wellness event ushers in the New Year:
The Art & Science of Cuisine

17 Salk Science and Music series
18 A history of the Salk
Salk hosts the second annual 5K Walk for Salk
and Explore Salk open house

Liz Hincks
Web Editor

19 Innovative research earns Salk scientist EUREKA award

Joe Belcovson
Photographer

Promising new research earns Salk scientist Career
Development Award

Mike Sullivan
Videography

Salk scientist receives grant for breast cancer research

Kat Kearney
Media Relations Manager
Máximo Escobedo
Senior Designer
studio L.
Graphic Design

20 Legacy Campaign accelerates: Salk supporters
encouraged to join

21 Salk Institute Board of Trustees elects three visionary
business leaders

22 Tatyana Sharpee receives NSF CAREER award
Salk scientist receives CIRM award

Visit the Salk Institute at www.salk.edu

underlying circuit architecture of the brain

27 Potent mechanism helps viruses shut down body’s
defense system against infection

28 Scientists help explain visual system’s remarkableability to recognize complex objects

29 Drug blocks light sensors in eye that may trigger
migraine attacks
N E X T G E N E R AT I O N

30 Fear Factor! Kevin Curran puts fear under the
microscope and challenges notions of what itmeans to be afraid
PHILANTHROPY NEWS33 2013 Donor Honor Roll
65 Salk science leads to discoveries
66 Women & Science events entertain and inspire
67 Back to Basics: Spicing up Alzheimer’s
drug discovery

68 Salkexcellerators
70 Pedal the Cause San Diego
71 Insider’s View

InsideSalk is printed on recycled paper.
CALENDAR

InsideSalk is published by the Salk Institutefor Biological Studies. We welcome yourinput. Please send comments tocommunications@salk.edu or contact
the communications department
at 858.453.4100 x1226.

Back CoverDear Friends,“OLD AGE,” THE ACTOR AND ENTERTAINER MAURICE CHEVALIER IS
reported to have said, “isn’t so bad when you consider the alternative.”
And Chevalier, who continued performing until two years before his
death at 83, presumably knew a thing or two about aging with grace andgood health.
But millions of people stricken with the diseases of old age—
Alzheimer’s, Parkinson’s, cancer, cardiovascular disease and more—are
not as lucky. For them, growing older can be fraught with physical andcognitive difficulties that undermine their quality of life. Earlier this year,
a government report projected that 13.8 million Americans will develop
Alzheimer’s disease by 2050, with the associated costs of care reaching$1.1 trillion. And those are the figures for just one condition! Clearly
it’s critical for society that we develop new interventions for age-relateddiseases that allow people to remain healthy and vigorous foras long as possible.
This issue of Inside Salk celebrates Salk research into healthy aging.
We are fortunate to have many scientists at the Institute who areinvestigating the basic mechanisms behind aging, making importantdiscoveries that are advancing our understanding of growing older. As
you probably know, healthy aging is one of the four scientific initiatives
underlying the Campaign for Salk, and I think it’s safe to say that it’s one
in which everyone has a stake. I hope you’ll enjoy reading about the workof Martin Hetzer, Juan Carlos Izpisua Belmonte and Jan Karlseder in our
cover story and gain a new appreciation for what the campaign means for
cutting-edge Salk research.
In fact, it’s been a remarkable several months at the Institute, withmany of our researchers publishing significant papers in major journals.
We are thrilled to report on some of the highlights in the following

William R. Brody

pages. Satchin Panda, for instance, has discovered a new molecule with
implications for migraines. Ed Callaway has produced novel insights
into how specific brain regions interconnect, and Sreekanth Chalasani
has discovered a previously unknown flexibility in neural circuitry andits influence on behaviors in model organisms. Also in neuroscience,
Joseph Ecker and Terrence Sejnowski have helped elucidate how
information in the genomes of cells in the brain is controlled from fetal
development to adulthood, and Tatyana Sharpee and John Reynolds
have demonstrated the complexities of decoding images made ofboth simple and intricate elements. In cell biology, John Young andGreg Lemke have discovered a new mechanism that may prove effectiveat clearing viruses from cells, and Lei Wang has developed a new tool
for protein engineering.
Your friendship and especially your support have been instrumental
in these breakthroughs, and as you peruse the magazine, I hope you’ll
think about what the findings of our scientists may ultimately mean toall of us and how you have helped bring them about. On behalf ofeveryone at the Institute, thank you for being such an important partof the Salk community.

William R. Brody, M.D., Ph.D.
President, Salk Institute
Irwin M. Jacobs Presidential Chair

Also in this issue: 2013 Donor Honor Roll

Where cures begin.

Salk Institute 01| 14

ON THE COVER
A lot changes in our bodies from infancy to our golden years, and science is just now beginning to decipher
what it means to age at the molecular level. The goal is to increase our “healthspan,” the amount of time
during our lives that we remain healthy and active.
Inside Salk February 2011www.salk.edu

www.salk.edu
Inside Salk 1 | 14 Executive
Message53

4

Lead Story Inside Salk 1 | 14

www.salk.edu

Ernest Juller was active and healthy well into his ninth decade. Salk scientists are exploring why some people have such a long ‘healthspan.’

THE SCIENCE OF

HEALTHY

AGING
What was Ernest Juller’s secret? In his 97 years, Juller was rarely sick, hardly saw a doctor and, until the very
end of his life, remained healthy, active and a gardener of particular persistence. Was it his daily glass of whitewine? Was it his regular leisurely walks in the Austrian forest? Or maybe his exceptional vitality stemmed fromthe same tenacity that kept him, year after year, attempting to grow an alpine forest in lowland Austria.
“He lived in a region situated at a much lower
altitude than Alpine plants typically grow,”recalls Juller’s grandson, Jan Karlseder, aprofessor at the Salk Institute. “He was nevercompletely successful with his Alpine garden,
but that didn’t deter him. He was a botany
professor, and he loved mountain plants. It’s
impossible to say exactly what kept him healthy
and active for so long—maybe it was good genes.
If so, I hope he passed them on.”For most of us, explaining the mystery ofpeople like Juller, who live remarkably longand healthy lives, is a matter of making casual
observations. We catalog aspects like diet,exercise, sleep and other salubrious elementsof a person’s life as we attempt to identify theirformula for success. For Karlseder and otherscientists at Salk, however, deciphering thesecrets of healthy aging is a full-time occupation. Equipped with cutting-edge scientific tools,
such as high-resolution imaging, whole-genome
sequencing and bioinformatics, they are exploring how our bodies age at the molecular level.
Line by line, they are filling in the blueprint forthe biological mechanisms that maintain ourcells and organs, repair damage from injuries
and fend off diseases as we get older.
The science of aging has never been more
important. Currently, about 40 million Americans
are over 65, and by 2030 those numbers are
expected to grow to more than 72 million. As
the proportion of older people rises, so too does
the incidence of age-associated disease, with its
attendant personal, social and economic costs.
Largely as a result of this trend, healthcare
spending is expected to increase by 25 percent
by 2030, and Medicare spending will grow from$555 billion in 2011 to $903 billion in 2020.
It is against this backdrop that the Salk Institute has launched its Healthy Aging Initiative
as part of the Campaign for Salk, the Institute’s
first-ever major fundraising campaign. Throughsupport for research on aging, the initiative seeks
to explain why aging is the number-one risk
factor for conditions such as neurodegeneration,
cancer, diabetes and cardiovascular disease.
But Salk scientists aren’t just asking why aging
often leads to illness. The initiative is also a

crucial step in developing therapies that target
the causes—not just the symptoms—of suchdiseases and disabilities.
“Every person’s medical history stems froma mix of genes, lifestyle and environment, butwhat we want to find are the common factors—atthe molecular, cellular and organismal levels—that allow some people to remain robust late into

From left: Salk scientists Makoto Hayashi, Anthony Cesare
and Jan Karlsederwww.salk.edu

Inside Salk 1 | 14 Lead Story5

life,” says Karlseder, the holder of Salk’s Donald
and Darlene Shiley Chair. “If we understandthese mechanisms, these programs that run
our cells and organs, we can use them to help
increase the human ‘healthspan,’ the length oftime people stay healthy during their lifetimes.”
Karlseder’s research centers around
telomeres—complexes that cap the ends ofchromosomes, the structures that contain our
DNA. Telomeres help protect and repair ourcells, and they play a central role in cellular
aging by shortening every time a cell divides,
a molecular method of marking time. When
telomeres become too short, they signal thecell to stop dividing and self-destruct, making
way for new cells.
Telomeres are also involved in DNA repair,a process by which cells fix damage done fromnormal physiological wear and tear and environmental factors such as UV light. Because tumors
attack the body by bypassing these safeguards,
scientists are also actively studying telomeres’
involvement in cancer.
Recent discoveries by Karlseder’s team
explain how telomeres serve as sentries,
keeping cells operating in an orderly fashionand protecting our bodies from cells containing damaged DNA. In one study, they showedthat telomeres begin to degrade rapidly when acell takes too long to divide—a sign of genetic
damage. This sends a warning signal that tells
the cell to shape up or ship out: repair its DNA
or self-destruct. It is a crucial check on cellular
growth that prevents cells with damaged DNA
from propagating. In another experiment, the scientists found that telomeres act as anchors thatorganize chromosomes as a cell divides. Under amicroscope, they observed that telomeres moveto the outer edge of a cell’s nucleus after thechromosomes are duplicated during cell division.

“Our cells aren’t simply bags containing an
unorganized mix of chemicals, but rather arecomplex three-dimensional machines, in which
the gears and wires are made up of molecules,”Karlseder says. “What we found suggests that
telomeres don’t just protect our cells; they help
orchestrate this molecular machinery in the
nucleus, which is the cell’s control center.”
In fact, Karlseder believes that telomeres
may play a central role in controlling how ourcellular programming—the genetic “software”
that runs our cells—changes as we get older.
The code that runs these programs is storedin our DNA sequences and in a collection of
extra-genetic chemical markers known as theepigenome, which can turn genes on and off,
thereby guiding cellular function. Integrated into
the chromosomes that house and organize thesecodes, telomeres are well placed to influence
how cells behave.
“The more we learn about telomeres,”
Karlseder says, “the more they appear to affectgene expression profiles and how the genome
morphs over time. By understanding thesemechanisms and learning how to influence them,
we may be able to intercede in the genomic andepigenomic programming that changes withaging. The idea would be to bolster the cellular
programs that protect and renew our bodies andstifle those that lead to premature aging.”
The research of Martin Hetzer, another Salk
professor studying the cellular roots of aging,
focuses on another important component of acell’s nucleus: the molecular gates, known as
nuclear pores, that allow the genetic control
center inside the nucleus to communicate withthe cellular machinery outside the nucleus, inthe region known as the cytoplasm. These poresalso protect the valuable genetic material fromtoxins found in the cytoplasm.

Hetzer’s team found that nuclear pores ofneurons contain certain proteins—which theydubbed extremely long-lived proteins (ELLPs)—
that have a remarkably long lifespan. Whilemost proteins last a total of two days or less, theresearchers identified ELLPs in the rat brain thatwere as old as the organism. This was the firsttime scientists had discovered an intracellularcomponent made up of molecules of this age,and their results suggested that the proteinslasted an entire lifetime without being replaced.
The longevity of ELLPs may help explainin part why brain function often declines as
people age. Previous studies by Hetzer’s group
showed that the nuclear pores weaken over time,allowing proteins to leak from the cytoplasm into
the inner sanctum of the nucleus. For instance,in older cells a protein called tubulin, whichshould be found only in the cytoplasm, gums up
the nucleus with long filaments. Associated withseveral neurodegenerative diseases, including
Parkinson’s, the filaments are found in the substantia nigra of many Parkinson’s patients, thepart of the brain that is involved in dopamine
production and that is affected by the condition.

Above: Martin Hetzer, professor, Molecular and Cell Biology Laboratory
and Emily M. Hatch, research associate
Opposite page, left to right: Martin Hetzer, Juan Carlos Izpisua
Belmonte, and Jan Karlseder

6

Lead Story Inside Salk 1 | 14

www.salk.edu

www.salk.edu

Inside Salk 1 | 14 Lead Story7

“We are curious why someelderly people seem relatively
unaffected by aging whileothers suffer from Parkinson’s,
Alzheimer’s and other”neurodegenerative disorders.
– MARTIN HETZER

8Lead Story Inside Salk 1 | 14

www.salk.edu

“What we think is happening is that ELLPs
deteriorate over the years and aren’t replaced,
which leads to dysfunction and vulnerability,”says Hetzer, who holds the Jesse and Caryl
Philips Foundation Chair. “It’s as if you regularly
take your car in for routine maintenance, but
one critical component was never replaced or
repaired. Eventually, that part will stop working,and that will have a cascade of effects, causing
the whole engine to go haywire.”
The deterioration of proteins may extend
beyond malfunctioning nuclear pores. Unlike
cells of the skin or other high-turnover areas of
the body, most of our neurons stay with us ourwhole lives. Other important components ofneurons may contain ELLPs and thus may besimilarly prone to wear and tear. In addition to
being embedded in the membrane surrounding
the nucleus, ELLPs are found on the plasma
membrane, the outermost surface of the cell.
They are also part of the chromatin, the bundles
of DNA and proteins found inside the nucleus,
which help to organize and control the functionof a cell’s genetic operations. In each case,
ELLPs serve a vital role in coordinating the
dizzying array of cellular activity that keeps ournervous system healthy.
“The reason we keep neurons so long is thatit’s important to have consistency; otherwise
we wouldn’t be able to learn and remember orto respond quickly to our environment,” Hetzer
says. “If we had to replace neurons all the time,
it would constantly interfere with our ability tofunction in the world. But stability comes at a
cost: it tests the durability of those neurons.
We know that genetic activity changes withage, and we think that results in part fromdeterioration of nuclear pores and other longlived cellular components.”
Like Karlseder, Hetzer is curious why someelderly people seem relatively unaffected bywww.salk.edu

aging, while others suffer from, Parkinson’s,
Alzheimer’s and other neurodegenerative
disorders. Through fully understanding how
certain people maintain normal function
and ward off disease, his team hopes to identify
and possibly bolster genetic and epigenetic
mechanisms that protect us as we age.
Other Salk scientists, such as Juan Carlos
Izpisua Belmonte, holder of the Roger Guillemin
Chair, are looking to our most immature cells
to explain what it means to get old. Izpisua
Belmonte’s lab studies how stem cells differentiate and give rise to over 200 cell types that
constitute the human body. This research not
only helps explain how our bodies maintain andheal themselves, but also offers the possibilityof using stem cells in regenerative medicine.
In one study, Izpisua Belmonte’s team
generated induced pluripotent stem cells(iPSCs) from skin cells obtained from patientswith Hutchinson-Gilford progeria syndrome,a condition which causes them to age eight to
ten times faster than the rest of us. The Salk
scientists then differentiated the stem cells into
smooth muscle cells displaying the telltale signsof vascular aging. In addition to providing insight
into Hutchinson-Gilford progeria, the study
offered a new method for studying age-relateddisease in the laboratory at an accelerated pace.
More recently, Izpisua Belmonte’s groupused iPSCs to generate neurons that exhibitedcharacteristics of Parkinson’s disease due tomutant genes inserted into the cells’ DNA.
This allowed them to study the molecularunderpinnings of the disorder in the laboratory,
overcoming the difficulty of obtaining humanneurons for experiments. His lab is also using
iPSCs to study Werner syndrome, a prematureaging condition that more closely resembles
normal aging, compared to Hutchinson-Gilford
progeria. Using these laboratory models, he andhis team are studying the links between genetic
instability, aberrant epigenetic signatures andcellular aging. Like Karlseder and Hetzer, Izpisua
Belmonte emphasizes that studying the normal
process of aging is crucial to understanding how
things can go wrong.
“Pluripotent stem cells give rise to all thetissues and organs in our bodies, and stem cells
continue to repair and replace old cells throughout our lives,” he says. “If we know precisely
how this happens—the exact molecular mechanisms—we might be able to boost this capacity
for self-healing.”
Karlseder offers Ernst Juller as an example
of what could become the norm if the science
unravels the mysteries of healthy aging. “Obviously, advances in science and medicine haveplayed a large role in helping us live longer,”says Karlseder. “Now we need to focus on
keeping us healthy longer. My aspiration is tostay as healthy as my grandfather as I get older,and I think the science we’re doing now can help
make that happen.”

From left: Emmanuel Nivet and Juan Carlos Izpisua Belmonte.
Seated: Ignacio Sancho Martinez
Inside Salk 1 | 14 Lead Story

9

One on one with…

Jan Karlseder
10

Lead Story Inside Salk 1 | 14

www.salk.edu

JAN KARLSEDER, HOLDER OF SALK’S DONALD AND DARLENE SHILEY CHAIR, STUDIES THE
complex relationship between aging and telomeres, the protective ends of chromosomes, as wellas such aging-related diseases as cancer.
A professor in Salk’s Molecular and Cell Biology Laboratory, Karlseder, along with his team, hasdiscovered that the relationship between telomeres and cancer extends much further than previously
believed. Their research has explained the process by which a class of anti-cancer drugs known as
mitotic inhibitors kills cells: exposure to mitotic inhibitors causes telomeres to lose their protectivefunction, and the cells respond with stress signals that eventually lead to the death of cancer cells.
Karlseder believes that continued research into the telomeres’ functions within cells will lead to an
ability to influence the aging process and, as a result, to the restriction of cancer cell growth.
A recent discussion with Karlseder reveals how, in the lab as well as his personal life, he pursues “thebigger picture” by addressing the smallest details.

Your grandfather was a scientist in Austria. Did that
influence your decision to go into science?
Yes, definitely. He was a botanist who studied alpine plants.
He used to take me and my brother into the forest and tell
us about all the plants. It instilled in us a curiosity about
the natural world, and both my brother and I still love theoutdoors. It also gave us a do-it-yourself mentality. My brother, who still lives in Austria, is a serious mushroom hunterand brews his own schnapps. The schnapps varieties are
actually really good.

www.salk.edu

Your grandfather lived a long, healthy life andstayed active until the very end. Why do some people
get so lucky?
These things are very circumstantial. Good genes, probably. He didn’t exercise rigorously, but he stayed active
walking and gardening. One thing about my grandfather
was that stress was unknown to him. He had the attitude
that if something couldn’t get done today, it could wait until
tomorrow. Nearly every day, he drank a glass of the local
white wine, for which that area of Austria is famous. But
really, it’s impossible to know.

Inside Salk 1 | 14 Institute News

11

Cactus garden at Karlseder’s house in Ramona, California.

But your research is helping us to understand aging?
We’re learning a lot about how our cells and organs age. Telomeres control
a lot more than just the number of times a cell divides. They play a rolein arranging chromosomes in a certain order so that they can talk to eachother. It’s very well-controlled, certainly not random, so there must be amechanism behind this process. If we can identify this mechanism, then I
think we’ll be able to address the often coordinated onset of age-associateddiseases. I have terrific people working in my lab, and we’ve shown thatthe deeper we dig, the more we realize how these very localized processes
affect the entire cell and therefore the organ and after that the organism.
There’s always a bigger picture.

Away from your lab, you spend a lot of free timeworking on Land Cruisers. What is the attraction?
The attraction came about after moving to San Diego. I fell in love with thesouthwestern desert and the Mexican desert, and I wanted to explore theseareas. I met some others who shared that interest, and the general agreement was that if you don’t want to break down out there you must have a
Toyota Land Cruiser. If you look at the wildest continents of the world, such
as Africa and Australia, you don’t see too many Jeeps; you do see a lot ofLand Cruisers. They are very durable trucks. So I bought a Land Cruiser andI drove it to Mexico. And of course it broke down. That was because it was
old and I didn’t know what I was buying. That’s when I decided that if I was

12

Institute News Inside Salk 1 | 14

going to do this, I needed to know a whole lot more about these vehicles.
I met a good guy, a sort of hobby mechanic, and we became friends andstarted working on them together, rebuilding engines, taking transmissions
apart and such.

How many Land Cruisers have you built?
Just for my use, at least six. I have one right now that’s a diesel. Diesels
have become our specialty. They get much better gas mileage, which isimportant when you’re traveling through the remote areas of the desert.
And the diesel engines are usually more reliable, too. But they’re difficult
to get. They were never sold in the U.S. You could get them in Canada fora while but not now. I just put an Australian diesel engine in my 1996
Land Cruiser. Over the past 11 years, I think I’ve logged about 100,000
miles in Baja.

What was your most harrowing moment?
I took a trip with my brother and a friend. We were going to try a new routefrom the Pacific Ocean to the Sea of Cortez, and it was through some reallyhigh mountains. We had two vehicles, and at one point we overlooked a
big rock, and the Toyota Tundra got hung up. That ripped out the rear axle
and tore the driveshaft in two. So, there we were in the middle of absolute
nowhere, high in the mountains, and we didn’t know what we were goingto do. We thought about piling all of our stuff into the one vehicle and justdriving away, leaving the Tundra. But then we took some time to put up

www.salk.edu

Karlseder and friend Mike Hein work on one of their overlanding vehicles.

some shade—it was scorchingly hot—and think about the problem, and we
decided, “Hey, we can fix this.” We had a few tools with us, but somesockets were missing, so I ended up driving to Loreto, which was six hours
away. When I got back, we lifted up the rear of the truck and tried to push
the axle into place, but it was too heavy. So we put the truck in front wheel
drive and drove backward, doing our best to center the truck over the axle.
Then we managed to rig up something to bolt it into place. It was on thattrip that we discovered the most important tool of all: a really big hammer.
We used that to fix the driveshaft. It was a little unbalanced when we weredone but it got us back to San Diego without a hiccup. You know, you canwork yourself out of a lot of problems if you have at least a remote idea ofwhat you’re doing.

What keeps you going back to Baja California?
It is absolutely beautiful there, completely deserted. You have a 1,200-mile
stretch of land that no one has spoiled. In many places there is not a single
person around, and there probably hasn’t been a single person around in amonth. It’s incredibly peaceful. You can sit on a beach and just think. No
email, no cell phones. You know that no one’s going to bother you. It’svery relaxing.

Do you think about science when you’re there?
All the time. You get a distance, you know. And sometimes you actually getsome very good ideas just sitting on the beach.
www.salk.edu

Karlseder estimates that he’s logged more than
100,000 miles of driving during his rugged expeditions
to Baja.
Inside Salk 1 | 14 Institute News

13

SYMPHONY at SALKAn enchanting way to support science and education
HIGH ABOVE THE PACIFIC OCEAN, UNDER A CANOPY OF STARS,
the Institute’s famed courtyard was transformed into a spectacular concert venue on August 24, for the 18th annual Symphony
at Salk. Award-winning singer and actress Katharine McPhee, thefeatured guest artist, performed a diverse set of songs ranging fromclassic Cole Porter to R&B soul and pop music, accompanied by the
San Diego Symphony under the baton of returning guest conductor
Thomas Wilkins.
Katharine McPhee and Maestro Thomas Wilkins

14

Institute News Inside Salk 1 | 14

Before the concert, guests were treated to a gourmet dinner, created
for the event by celebrated chef Jeffrey Strauss, owner of the criticallyacclaimed Pamplemousse Grille.
The unforgettable evening raised nearly $900,000 for the Institute’s
scientific research and educational outreach program.

Katharine McPhee

www.salk.edu

Salk celebrates Irwin Jacobs’s 80th birthday
ON THE EVENING OF OCTOBER 14, SOME
140 people gathered in the Salk courtyard
to celebrate the 80th birthday of board
chairman Irwin M. Jacobs and recognize his
many accomplishments. Those attending
included personal friends of Jacobs and his
wife, Joan, as well as Salk faculty, donors,
trustees and local business leaders.
The celebration capped a daylong
symposium in Jacobs’s honor, titled“Unraveling Biological Complexity:
Transforming Research through Innovation,
Leadership and Philanthropy.” Some of theInstitute’s most distinguished researchers
spoke about discoveries from their labs,
including Joseph Ecker, Inder Verma,Fred Gage, Joanne Chory, Ronald Evans,
Thomas Albright, Juan Carlos Izpisua

Belmonte and Terrence Sejnowski. The
symposium concluded with a keynote lecture
by MIT professor Robert Langer, one of theworld’s leading researchers in biotechnology.
At the evening’s cocktail reception, Verma,
serving as master of ceremonies, welcomed
the guests and introduced a video highlighting
the tremendous impact Jacobs has had
during his lifetime, both during his careerat Qualcomm, Inc., which he cofounded,and through his numerous philanthropic
activities. Salk president William R. Brody
led the crowd in a toast to Jacobs; thenformer vice president Al Gore spoke about
Jacobs’s rise to success.
Executive vice president Marsha Chandler
introduced the musical performers for theevening: Geoffrey Keezer, a jazz pianist andtwo-time Grammy nominee who had recently
recorded an album at the Jacobs home, andJesse Palter, a vocalist and composer who
performed a number of songs, ending withthe classic “Hey, Big Spender.” At this point
Jacobs was led onto the stage and presented with a birthday cake and a gift speciallychosen by Salk faculty—an early edition ofCharles Darwin’s On the Origin of Species.
After Jacobs thanked his friends andfamily for sharing the special day with him,
Verma concluded the evening by reading apoem he’d composed for the occasion. It
was a heartwarming tribute to a man who
has done so much for the community andfor the Salk Institute.

Salk earns third consecutive
Charity Navigator four-star rating
FOR THE THIRD STRAIGHT YEAR, CHARITY NAVIGATOR, THE
nation’s largest evaluator of nonprofit business and financial operations,has awarded Salk a four-star rating for “sound fiscal management.”
This top designation was determined after a team of professional
analysts examined tens of thousands of nonprofit financial documents.
“We are proud to announce that the Salk Institute for BiologicalStudies has earned our four-star rating for its fiscal health andwww.salk.edu

commitment to accountability and transparency,” said Ken Berger,
president and CEO of Charity Navigator. “Only 11 percent of thecharities we evaluate have received our highest rating three years in arow, indicating that the Salk Institute for Biological Studies executes
its mission in a fiscally responsible way and outperforms most othercharities in America. This ‘exceptional’ designation… demonstrates tothe public [that] it is worthy of their trust.”

Inside Salk 1 | 14 Institute News

15

Inaugural Wellness Event Ushers in the New Year:

The Art and Science of Cuisine

From left: Professor Ron Evans and Chef Nathan Coulon

Notable chef, author and restaurant owner Su-Mei Yu stirs things up with Salk scientist Geoff Wahl.

FUEL FOR BOTH THE MIND AND BODY WILL BE THE THEME IN
January when the Salk Institute introduces The Art & Science ofCuisine, blending the most recent nutritional discoveries with novel
culinary concepts.
Guests at the mixer will have the opportunity to meet some of San
Diego’s most innovative chefs, sample their cooking and learn how to
optimize nutrition in home-cooked meals. Complementing the farewill be up-to-the-minute information from Salk scientists about thelatest research into the links between nutrition and health, and the role
diet may play in disease risk.
San Diego has long been known for its dynamic restaurant scene,
and the city regularly tops lists for active living. Many local chefs
have made it a priority to serve the freshest, most healthful fare—foodthat not only pleases the palate but nourishes the body. Deborah Szekely,
the honorary chair of the event, cofounded the renowned spas The
Golden Door and Rancho La Puerta and at 91 embodies the power ofmindful eating. Szekel has written three cookbooks and recently launched
Wellness Warrior, a nonprofit organization to champion health issues.
Featured chefs at the event will include:

Joy Houston—a certified Raw Food Nutrition Educator who helps people
incorporate more fresh foods into their everyday diet. She has beenfeatured on TV and in magazines for various aspects of healthy eating,raw food, superfoods and juicing.
Denise Roa—chef at Rancho La Puerta, who fuses the culinary and cultural
heritages of her own life with the healthful “spa cuisine” dining pioneeredby Rancho La Puerta. The resort has never focused on caloric deprivation,
but instead celebrates the seasons of its own farm and organic produce
suppliers with a cuisine that is colorful, zesty, and satisfying—the kindof food that fuels a life of vigorous activity.
Su-Mei Yu—owner of the popular Thai restaurant Saffron. Yu serves only
the freshest seasonal ingredients “to offer food for the body, mind andsoul.” Host of the TV show Savor San Diego, she is a passionate
advocate for the local food community.
The Art and Science of Cuisine will take place at the Institute on
Wednesday, January 22, 2014. For more information, visit www.salk.edu/
cuisine or contact cuisine@salk.edu or call 858-453-4100 ext. 1846.

Nathan Coulon—executive chef at True Food Kitchen, who takes popular
trends in cuisine and pairs them with healthy living. His menu features
seasonal recipes that emphasize locally grown organic ingredients.
Isabel Cruz—owner of three restaurants in San Diego and two in Oregon
and known for her innovative blending of Latin and Asian cuisines. Her
recipes produce meals that are not only delicious but are good for you.

16

Institute News Inside Salk 1 | 14

www.salk.edu

Awarding-winning pianist Sean Chen played to a sold-out audience at the inaugural Salk Science and Music Series concert held at
the Institute on October 6.

Salk Science and Music Series

Sean Chen

Program combining concert performances and scientific talks ‘Amaze & Inspire’
INSPIRED BY A MAGNIFICENT GIFT OF A CONCERT STEINWAY PIANO
from generous Salk benefactor Conrad Prebys, the Institute has initiatedthe Salk Science and Music series—an ambitious program that melds
both amazing science and inspiring music for the San Diego community.
The six-concert series, which debuted on October 6 to a sold out audience, will run through May of 2014. The program provides a venue tofeature some of the hottest emerging classical and jazz musicians, andalso includes fascinating scientific presentations of the latest discoveriesoccurring in Salk labs by our world-renowned faculty.
Each concert begins at 4 p.m. With a 40-minute musical performance,
followed by a 15-minute scientific talk, and then more music, concluding
at 5:45 p.m. For tickets and information: www.salk.edu/music

2014 FEATURED PERFORMERS
Jan. 26:

Pianist Yoonie Han (Fulbright Concerto Competition
winner) and scientist Ron Evans (Professor and Director,
Gene Expression Laboratory)

Feb. 23:

Vibraphonist Joe Locke with pianist Geoffrey Keezer andscientist Tom Albright (Professor and Director, Vision
Center Laboratory)

March 16: Violinist Sean Lee (Paganini Competition winner) withpianist Karen Joy Davis and scientist Marc Montminy(Professor and Director, Clayton Foundation Laboratories
for Peptide Biology)
May 18:

Pianist Fei Fei Dong (Van Cliburn finalist) and scientist
Clodagh O’Shea (Associate Professor, Molecular and Cell
Biology Laboratory)
For more information, call (858) 453-4100 ext. 2098;
visit salk.edu/music; or email music@salk.edu

President’s Club members receive free admission and premier seating
to all Salk Science & Music Series concerts and are invited to attend
a private reception following each performance hosted by President
William Brody and the featured Salk scientist. Visit www.salk.edu/
presidentsclub or call 858-453-4100 x 1405 to learn more.
Fred ‘Rusty’ Gage presented an intriguing scientific talk at the debut event.
www.salk.edu

Inside Salk 1 | 14 Institute News17

A historyof the Salk

Suzanne Bourgeois“

Jonas Salk should be recognized
for two major achievements:
One is the polio vaccine and theother is the Salk Institute.
– SUZANNE BOURGEOIS”SUZANNE BOURGEOIS, PROFESSOR EMERITUS AND FOUNDING DIRECTOR
of Salk’s Regulatory Biology Laboratory, has written a new book documenting the
dynamic history of the Institute and the key players who played a part in its creation.
Titled Genesis of the Salk Institute: The Epic of Its Founders, Bourgeois retells thestory of how and why, born far apart, the founders of the Salk Institute eventuallygathered in La Jolla in the early 1960s to create an exceptional institution.
“Jonas Salk should be recognized for two major achievements: One is the polio
vaccine and the other is the Salk Institute,” says Bourgeois. The new book is apersonal account of the origins and early years of the Salk, and Bourgeois crafts anengaging study that draws on her involvement with the Institute since its founding
and on related archives, interviews and informal conversations. “I think I’m probably
the only one who has daily records of what happened,” she says.
The volume discusses the people who founded the Institute and built a home
for pioneering research—leading scientists of the time as well as non-scientists ofstature in finance, politics, philanthropy, publishing and the humanities. The events
that brought these individuals together, the historic backdrop in which they worked,
their personalities, their courage and their visions, their clash of egos and theirpersonal vanities are woven together in a rich, engaging narrative about the foundingof one of the world’s premier research institutions. Released last month, the book isavailable through University of California Press and Amazon.

Salk hosts the second annual 5K Walk for Salk and Explore Salk open house
MARK YOUR CALENDARS FOR APRIL 12,2014 to join in Salk’s second annual Step
Into Discovery day. This year the date isespecially significant. On April 12, 1955,
Jonas Salk announced the discovery of
the polio vaccine, forever transforming lives
around the world.
Last year’s inaugural event drew over a
thousand people to the Institute and this year
promises to bring even more supporters eager
to experience the event.
The day will be filled with activities startingwith the 5K Walk for Salk. Participants will start

18

Institute News Inside Salk 1 | 14

at the courtyard and walk through a coastal trek
on Torrey Pines Road that concludes back on the
Salk campus.
The fun doesn’t end at the finish line.
It continues at the Explore Salk open housefeaturing exclusive behind the scenes tours ofscience and research labs. The courtyard will
be filled with informational booths and handson activities for children and adults, including
special presentations by the Salk Education
Outreach Program.
Step into Discovery supports the Salk’s
leading edge research and important education

outreach programs including the Mobile Science
Lab, High School Scholars and High School
Science Day—dynamic programs that bringthe excitement of scientific discovery to
thousands of students and teachers throughout
San Diego County.
For more information please visit:www.salk.edu/stepintodiscovery

www.salk.edu

Innovative research earns Salk scientist EUREKA award

Axel Nimmerjahn

THE NATIONAL INSTITUTES OF HEALTH (NIH)
have selected Axel Nimmerjahn for a highly selective EUREKA (Exceptional Unconventional Research
Enabling Knowledge Acceleration) grant. The EUREKA
awards provide support for innovative, high-riskbiomedical research initiatives with the potential forachieving significant health impact.
An assistant professor in the Waitt Advanced
Biophotonics Center, Nimmerjahn holds the Richard
Allan Barry Developmental Chair. The award, totaling$1.38 million over four years, will support his goal of
better understanding the relationship between spinal
cord physiology and brain activity and behavior. Data
from this research should foster development of
new treatment and rehabilitation strategies for spinal
cord injury, tumors, infections and neurodegenerative

diseases such as amyotrophic lateral sclerosis (ALS)
and spinal muscular dystrophy.
The EUREKA program was conceived specifically to help scientists such as Nimmerjahn test new,innovative ideas or tackle major methodological or
technical challenges. “EUREKA awards reflect the
NIH’s continued commitment to funding transformative
research, even if it carries more than the usual degreeof scientific risk,” says NIH director Francis S. Collins,
M.D., Ph.D. “The grants seek to elicit those ‘eureka
moments’ when scientists make major theoretical or
technical advances.”
Nimmerjahn is only the second Salk scientist to
be honored with this prestigious award. Fred Gage,a professor in the Institute’s Laboratory of Genetics,
was the recipient of a EUREKA grant in 2009.

Promising new research earns Salk scientist
Career Development Award
THE JUVENILE DIABETES RESEARCHFoundation (JDRF) has given Salk scientist
Mark Huising a five-year, $750,000 Career
Development Award for his study on how a novel
network of receptors in human islets receives
and integrates molecular signals. In preclinicalmodels, activation of these receptors has provento actually prevent diabetes.
The goal of Huising’s study, titled “Urocortin
3 Marks Mature Beta Cells and Prevents Diabetes,” is to understand how this protectionis accomplished. “Despite years of research,”
he says, “significant gaps remain in our understanding of the way the islet receives andintegrates signals from a wide variety of sources.
We envision that among these networks of signaling molecules plenty remain that are unknown
and can lead to novel strategies to treat or cure
type 1 diabetes.”

Type 1 diabetes is a chronic condition inwhich the pancreas produces little or no
insulin. Although the condition, which usuallyappears during childhood or adolescence, canbe managed, it requires a daily juggling act.
Food, exercise and insulin must be carefullybalanced with scheduled blood sugar checks
and insulin injections. A diagnosis of diabetes
is also a major risk factor for later complications
such as cardiac failure, kidney problems andlower limb amputations. To date, type 1 diabetes
has no cure, making Huising’s research all themore exciting.
The JDRF is the leading global organization
funding type 1 diabetes research. It currently
sponsors $530 million in scientific research in
17 countries and particularly seeks researchers
who specialize in translational research. The
primary purpose of the Career Development

Mark HuisingAward is to “attract qualified and promisingscientists early in their faculty careers andto give them the opportunity to establish
themselves” in areas pertinent to diabetes
research. Career Development Awards are highly
competitive and awarded to only a handful ofpeople each year.

Salk scientist receives grant for breast cancer research
THE SUSAN G. KOMEN FOR THE CURE
organization has awarded Geoffrey Wahl,
professor in the Salk Institute’s Gene Expression
Laboratory, a $225,000 grant to support his
breast cancer research.
Wahl, a Komen Scholar, has been working to
identify characteristics in triple negative breast
cancer cells. His research seeks to further our
understanding about what makes triple negativecancers so dangerous and resistant to traditional
therapies. He also hopes to discover new andbetter ways of eliminating these types of cancers.

The grant is part of $4.5 million in grants
recently awarded to California research organizations by Susan G. Komen for research thatexamines the role that environmental issues playin the development of breast cancer.
Susan G. Komen for the Cure was founded in1982 and has since invested more than $790
million in breast cancer research, making it thelargest nonprofit, non-government cancer
research-funding organizationin the United States.

Geoffrey Wahl
www.salk.edu

Inside Salk 1 | 14 Institute News

19

Legacy Campaign Accelerates:
Salk Supporters Encouraged to Join

JOE AND DIANA KALMAN SET IN MOTION A PLAN TO HELP

an easy decision now that has a tremendous impact on the future

people they’ll never meet. They worked with Cheryl Dean, seniorof biomedical research. It’s impossible to imagine all the good yourdirector of planned giving at the Salk Institute, to arrange a legacy

money may do to improve future lives.”

gift, directing through their estate documents that funds be

Those who include the Salk in their estate planning are

passed on to the Salk Institute. Thanks to their foresight anddesignated Partners in Research. It’s a fast-expanding group,

generosity, sometime in the future, a child with bone cancer may

with 61 new members having joined since the campaign began.

receive a novel, life-saving treatment or a young postdoctoral

Partners receive invitations to specially planned lectures andresearcher may receive the funding for an ambitious research project.

tours, as well as exclusive receptions and events. And, of course,

Or one of the many bustling laboratories at the Salk may receive

they’re kept abreast of the latest discoveries by Salk’s scientists—

state-of-the-art research equipment, tools crucial to deciphering

a common occurrence.

the cell’s mysteries. “It’s just what we wanted to do,” Diana said,“to support the science of healthy living.”
More and more, thoughtful, visionary individuals such as Joe andWhether it’s a charitable remainder trust, a simple bequest or atransfer of property, (among numerous other possibilities for giving),
the team at the Salk can help you transform a current asset into

Diana Kalman are including the Salk Institute in their estate plans.

a future cure. They encourage you to ask questions. They’re readyIt’s an effortless way to make a difference in the future, to leave ato help. For more information about the Legacy Campaign andlegacy. The world can be a different place—a better place—for yourthe benefits of becoming a Partner in Research, please contact

having been here. Dean says that directing funds to the Salk Institute

Cheryl Dean, Esq. at 858.500.4884 or cdean@salk.edu.

means that “your money performs for you in perpetuity. You can make

“It is part of wisdom to ask not only are we being good citizensof the world today, but are we being good ancestors?”

20

Institute News Inside Salk 1 | 14

www.salk.edu

Elizabeth “Liz” Keadle

David F. Hale

Alan D. Gold

Salk Institute Board of Trustees Elects Three Visionary Business Leaders
THE SALK INSTITUTE IS PLEASED TO
announce that Elizabeth Keadle, David F. Haleand Alan D. Gold have been elected to its Boardof Trustees.
“Liz, Alan and David each bring outstanding
records of entrepreneurial success and businessexpertise to Salk,” said Irwin M. Jacobs, Chairman of the Salk Institute Board of Trustees.
“We are greatly pleased to have them join our
Board of Trustees.”
Elizabeth “Liz” Keadle is an alumna of theInstitute and worked in the Peptide Biology
Laboratory with Salk scientist Wylie Vale whilea student at UC San Diego. She started as avolunteer and was hired to work on several
research projects, including Vale’s work withcorticotropin-releasing factor, which his group
discovered in 1981. Her experience at Salk led
to a career in the biotech business; she eventually joined Swedish biotech supply company
Pharmacia AB, where she rose to key technicaland business leadership positions. She also
became involved in the launch of the local
biotech company Invitrogen, which quickly grew
to become the world’s largest biotech researchsupply company and went public in 1999. Years
later, it was renamed Life Technologies andin 2013 was sold to Thermo-Fisher for $13.6
billion. An ardent supporter of Salk science,www.salk.edu

Keadle is a longtime Symphony at Salk sponsor
and created an endowment in support of theVale lab. She recently established the Wylie
Vale Chair as a lasting legacy to honor the latescientist; Paul Sawchenko, professor and headof Salk’s Laboratory of Neuronal Structure andFunction, currently holds the chair.
David F. Hale is chairman and chief executive
officer of Hale BioPharma Ventures, LLC, aprivate company focused on the formation anddevelopment of biotechnology, specialty pharma,
diagnostic, and medical device companies. He
also serves as executive chairman of Biocept,
Inc., a cancer diagnostic company working on
the detection and analysis of circulating tumor
cells. Previously, he was president and chief
executive officer of CancerVax Corporationfrom October 2000 through its merger in May
2006 with Micromet, Inc., where he served aschairman until its acquisition by Amgen Inc.
in 2012. Additionally, Mr. Hale is chairmanof Santarus, Inc., and a founding director andchairman of Conatus Pharmaceuticals, Inc.
He is a co-founder and chairman of numerous
other companies. Mr. Hale currently serves on
the board of directors of BIOCOM, which heco-founded, and the San Diego Economic
Development Corporation. He is a former member of the board of the Biotechnology Industry

Organization (BIO) and the Biotechnology
Institute. He is a co-founder and a director of
CONNECT, acts as chairman of the board oftrustees of Rady Children’s Hospital, and is amember of Rady School of Management Dean’s
Advisory Council.
Alan D. Gold is chairman and chief executive
officer of Biomed Realty, a publicly traded
REIT specializing in acquiring and managing
laboratory properties for lease to the life science
industry. Mr. Gold also served as president of
BioMed’s privately held predecessor, Bernardo
Property Advisors, Inc. He was a co-founderand served as president and as a director of
Alexandria Real Estate Equities, Inc. He wasmanaging partner of GoldStone Real Estate
Finance and Investments, a partnership engaged
in the real estate and mortgage business. He
also served as assistant vice president ofCommercial Real Estate for Northland Financial
Company, a full service commercial property
mortgage banker, and as Real Estate Investment
Officer–Commercial Real Estate for John
Burnham Company, a regional full service realestate company. He currently serves on theCampanile Foundation Board supporting San
Diego State University.

Inside Salk 1 | 14 Institute News

21

Tatyana Sharpee

Tatyana Sharpee receives NSF CAREER award
TATYANA SHARPEE, AN ASSOCIATE PROFESSOR IN THE
Computational Neurobiology Laboratory, has received a CAREER
award from the National Science Foundation (NSF) to fund upcoming
research in her lab. The CAREER award supports faculty who exemplify
the role of teacher-scholars through outstanding research, excellent
education and the integration of education and research within thecontext of the mission of their organizations.
Sharpee will receive $453,000 over the next five years to fund herstudy “Characterizing feature selectivity and invariance in deep neuralarchitectures.” In an effort to help elucidate the principles that makerobust object recognition possible, she will explore how an organism’s
neurons are able to demonstrate both “invariance,” which produces
a similar response to the same object even when observed from different
viewpoints, and “selectivity,” which requires different responses topotentially similar objects. The results of her study will help reveal thecommon principles of sensory processing in the brain and may ultimately
lead to improved designs of artificial recognition systems, including
sensory prostheses.

Salk scientist receives CIRM award
INDER VERMA, PROFESSOR IN THE LABORATORYof Genetics and American Cancer Society Professor of
Molecular Biology, received a $2.3 million grant from the
California Institute for Regenerative Medicine (CIRM) as
part of its Early Translational IV Research awards. The
program is designed to fund research that will help shift
stem cell research from the laboratory to practical use withthe development of new potential drug or patient therapies.
Verma, holder of the Irwin and Joan Jacobs Chair in
Exemplary Life Science, is one of the world’s leading
authorities on the development of viruses for gene therapy
vectors. He uses genetically engineered viruses to insert
new genes into cells that can then be returned to the body,where they produce the essential protein whose absence
causes disease. Verma and Salk colleagues developed
a gene therapy vector, based on a stripped-down version
of HIV that can deliver genes to non-dividing cells, whichconstitute the majority of the cells in our bodies. They haveused this vector successfully to deliver the clotting factor

22

Institute News Inside Salk 1 | 14

gene to laboratory animals and to transfer a therapeuticgene to retinal cells to mice with an inborn deficiency.
Verma’s lab is also studying two genes implicated infamilial breast cancer, BRCA1 and BRCA2, and recently
demonstrated that their action is linked to the cell’s
division cycle and that BRCA1 regulates gene activity.
CIRM was established in November 2004 with thepassage of Proposition 71, the California Stem Cell
Research and Cures Act. The statewide ballot measure,which provided $3 billion in funding for stem cell research
at California universities and research institutions, wasoverwhelmingly approved by voters, and called for theestablishment of an entity to make grants and provide
loans for stem cell research, research facilities,
and other vital research.

Inder Vermawww.salk.edu

Discovery Roundup

From left: Scientists Haiyan Ren, Lei Wang and Zheng Xiang

Salk scientists add new bond to protein engineering toolbox
PROTEINS ARE THE WORKHORSES OF CELLS,
adopting conformations that allow them to set
off chemical reactions, send signals and transport materials. But when scientists are designinga new drug, trying to visualize the processes
inside cells or probe how molecules interact
with each other, they can’t always find a proteinthat will do the job they want. Instead, theyoften engineer their own novel proteins to use inexperiments, either from scratch or by altering
existing molecules.
As reported in Nature Methods, researchers
in the lab of Lei Wang have developed a newtool for protein engineering: a way to add strong,
unbreakable bonds between two points in a
protein or between two proteins.

www.salk.edu

When a protein folds from a loose chainof amino acid building blocks into its active
three-dimensional structure, bonds andchemical interactions naturally form between
different parts of the chain to keep the structureassembled. Most are relatively weak, driven by
the electrochemical charges of different aminoacids. Stronger bonds, called disulfide bridges,
occur between pairs of cysteines, one particularamino acid. But for protein engineers, either
type of bond has had its own deficiencies. So
linking two parts of a protein in a predictableand permanent way has been notoriously hard.
Wang and his team wanted to be able toadd strong, irreversible bonds—called covalentbonds—to proteins to alter their shape, makethem more stable or attach them to one another.
So they began trying to create a new amino acid,different from the 20 that exist naturally.
They created dozens of possible amino acids
and tested each one to see if it bound with justthe right strength. After a series of tests, they
settled on a newly created amino acid called
p-2-fluoroacetyl-phenylalanine, or Fact, thendesigned three proteins using it in theirsequences. Tests of the proteins showed thatthey formed a covalent bond with Fact.
“I think anyone who is working on proteins, oranything related to proteins, could make use ofthis new technology,” says Wang. “It can provide
a novel way to control proteins or design proteinsto study basic biology.”

Inside Salk 1 | 14 Discovery Roundup

23

Discovery Roundup

From left: Marga Behrens, Eran Mukamel, Terry Sejnowski, Joseph Ecker

Unique epigenomic code identified
during human brain development
THE FRONTMOST PART OF THE BRAIN, THE FRONTAL CORTEX, PLAYS
a key role in our ability to think, decide and act. The brain accomplishes
all of this through the interaction of special cells such as neurons and glia.
We know that these cells have distinct functions, but what gives them
their individual identities? The answer lies in how each cell expresses theinformation contained in its DNA.
Changes in the epigenome, including chemical modifications ofDNA, can act as an extra layer of information in the genome and arethought to play a role in learning and memory, as well as age-related
cognitive decline. In a recent study, a team led by Joseph R. Ecker andTerrence J. Sejnowski showed that the landscape of DNA methylation, aparticular type of epigenomic modification, is highly dynamic in brain
cells during the transition from birth to adulthood, helping to understandhow information in the genomes of cells in the brain is controlled fromfetal development to adulthood.
In the study, published in Science, the scientists found that thepatterns of DNA methylation undergo widespread reconfiguration in thefrontal cortex of mouse and human brains during a time of development
when synapses are growing rapidly. They identified the exact sites of
DNA methylation throughout the genome in brains from infants throughadults and found that one form of DNA methylation is present in neurons
and glia from birth. Strikingly, a second form of DNA methylation that is24

Discovery Roundup Inside Salk 1 | 14

A new study by Salk researchers provides the first comprehensive maps of epigenomic changes in the brain
known as “DNA methylation,” a chemical modification of a cell's DNA that can act as an extra layer of
information in the genome. The study provides clues as to how specific genes are regulated in fetal, juvenile
and adult brain cells, and the findings form a critical foundation to explore whether changes in methylation
patterns may be linked to human diseases, including psychiatric disorders.
Image courtesy of Eran Mukamel, The Salk Institute for Biological Studies

almost exclusive to neurons accumulates as the brain matures, becoming
the dominant form of methylation in the genome of human neurons.
These results help explain how the intricate DNA landscape of brain
cells develops during the key stages of childhood. They also provide thefirst comprehensive maps of how DNA methylation patterns change in themouse and human brain during development, forming a critical foundationfor exploring whether changes in methylation patterns may be linked tohuman diseases, including psychiatric disorders.

www.salk.edu

Salk scientists found that insulin plays a role in mediating roundworms’ perceptions and behaviors. This image shows a C. elegans,the species of roundworm the Salk researchers studied.

Top: An odor-sensing neuron (named AWC and shown in green) in
the head of the worm was unexpectedly found to respond to salt
in the environment. Bottom: Higher magnification images of thisneuron before (left) and during (right) salt presentation. The neuron
expresses a calcium indicator that causes the neuron to light up(indicated by the white and warmer colors) when it is active; thesalt exposure significantly lit up this neuron, which revealed thecomplexity of the worm's sensory system.

Salk scientists Sarah Leinwand and Sreekanth Chalasani

Insulin plays a role in mediating worms’ perceptions and behaviors
AS IMAGING TOOLS AND TECHNIQUES HAVE IMPROVED, SCIENTISTS
have been building a detailed map of neural connections in the humanbrain, with the ultimate hope of understanding how the mind works.
But in order to decode perceptions and behaviors, it is also necessary toknow the routes that information takes in the brain. A recent study by
Sreekanth Chalasani, in collaboration with UC San Diego doctoral student
Sarah Leinwand, found a striking example of flexibility in neural circuitry
and its influence on behaviors in worms.
In the study, reported in Nature Neuroscience, Chalasani’s team built
on established research on the roundworm Caenorhabditis elegans that had
identified sensory neurons with distinct roles such as sensing temperature,
pheromones, salt and odors. Imaging worms that expressed geneticallyencoded indicators in their neurons, which caused the cells to light up
when active, they found the worms’ olfactory sensory neuron lit up after
exposure to an attractive but high concentration of salt. This revealed
that more than one type of neuron is involved in processing sensory cues;
previously it had been thought these were sensed only by single neurons.
Chalasani and Leinwand further showed that the olfactory neuron was crucial for the worm’s movement toward salt within a certain

www.salk.edu

concentration range and that a neuropeptide was being released by thesalt-sensing neuron to shape the animal’s behavior. Tracking olfactory
neuron responses to high salt in worms missing specific genes, they foundthat worms lacking the gene for an insulin neuropeptide known as INS-6
did not respond to increases in salt. Restoring this peptide reinstated theanimal’s normal responses to high salt.
It was a big surprise that insulin was the main signaling molecule
recruiting the olfactory neuron into a salt-sensing circuit. Neuropeptides
had been thought to modulate neuronal function over many seconds tomany minutes. But in this instance, it appears that the insulin is acting
in less than a second to transfer information from the salt-sensing neuron
to the neuron that normally responds to odor. Similar neuropeptide
communication may create flexible neural circuits that mediate thebehaviors of other animals and people, so Chalasani and Leinwand plan
to investigate whether other fast neural circuit switches exist in worms,
and if so, what signaling mechanisms they use.

Inside Salk 1 | 14 Discovery Roundup

25

Discovery Roundup

The microscope image shows nerve cells in the mouse brain that have been labeled with a modified rabies virus. These cells send directconnections to striatum, a region of the brain that regulates voluntary movement. The striatum is disrupted in degenerative disorders suchas Parkinson's disease and Huntington's disease.
Photo courtesy of Nicholas Wall.

High-resolution mapping technique uncovers
underlying circuit architecture of the brain
NEUROSCIENTISTS HAVE LONG SOUGHT TO
map individual neuronal connections to see
how they influence specific brain functions, buttraditional techniques have proven unsuccessful.
Using an innovative brain-tracing technique,a team led by Edward Callaway and Gladstone
Institute investigator Anatol Kreitzer has found a
way to untangle these networks. Their findings,
reported in Neuron, offer new insight into how
specific brain regions interconnect, while also
providing clues to what may happen, neuron byneuron, when these connections are disrupted.
The researchers used a sophisticated tracing
technique, pioneered by Callaway and known as
the monosynaptic rabies virus system, to assemble brain-wide maps of neurons that connect
with the basal ganglia, a region of the brain
involved in movement and decision- making.

26

Discovery Roundup Inside Salk 1 | 14

The system uses a modified version of the rabies
virus to “infect” a brain region, which in turntargets neurons connected to it. In their study,
the investigators activated the tracer genetically,
ensuring that it only turned on in specificneurons in the basal ganglia. This hugetechnological advance enabled them to follow
just the networks that connect to particularkinds of cells in the basal ganglia from otherparts of the brain.
Last year, Kreitzer and his team publishedresearch that revealed clues to the relationshipbetween two types of neurons found in the basal
ganglia, which act as opposing forces, with one
initiating movement and the other inhibiting it.
These neurons are also involved in decisionmaking, and dysfunctions in them are associatedwith addictive and depressive behaviors. The

findings provided a link between the physicalneuronal degeneration seen in movement
disorders, such as Parkinson’s disease, andsome of the condition’s behavioral aspects.
But the study left unanswered questions about
how other brain regions influence the functionof these neuron types.
When the monosynaptic rabies virus system
was applied in mouse models, the team could
see specifically how sensory, motor and reward
structures in the brain connected to the two
neuron types. The results will help decode how
this network guides the vast array of distinct
brain functions, as well as how dysfunctions indifferent parts of this network can lead todifferent neurological conditions, eventuallyalso suggesting solutions.

www.salk.edu

From left: John Young, Erin Lew, Greg Lemke, Anna Zagórska, John Naughton

Potent mechanism helps viruses shut down body’s defense systemagainst infection
IN THE IMMUNE SYSTEM, TAM RECEPTORS
are used by cells such as macrophages anddendritic cells to clean up dead cells. They
are also central inhibitors of the body’s innate
immune response to bacteria, viruses andother pathogens.
As reported in Cell Host and Microbe,
researchers in the labs of John A.T. Young andGreg Lemke have discovered that a substancecalled phosphatidylserine (PtdSer), found on
the surface of enveloped viruses (viruses withan outer wrapping of a lipid membrane), binds
to extracellular proteins and activates TAM
receptors on immune cells. In dendritic cells,
a type of immune cell that interacts with T and
B cells to initiate the adaptive immune response,
TAM receptor activation turns off a set of genes

www.salk.edu

called interferons that play a key role in antiviral
defense. The findings suggest a unique way inwhich TAM receptors contribute to the establishment of viral infection by disabling the interferon
response. As a consequence, the interferon-stimulated defense genes are not turned on, rendering the target cell more vulnerable.
This is a previously unknown mechanism
for enveloped viruses, which are very common,
to inhibit the body’s normal antiviral response.
Since PtdSer exposure seems to be a generalfeature of enveloped viruses, the researchers say
many different viruses may use the mechanism
to counteract the antiviral response in cells with
TAM receptors.
Understanding this mechanism will allow researchers to work on developing broad-spectrum

antiviral drugs that prevent viruses from shutting
down the interferon response in cells by blocking
TAM receptor activation. Young and Lemke
tested a small-molecule drug initially developed
for anti-cancer therapy that does just that, andwith other scientists around the country, they
are now testing other small-molecule drugs
that work, in large part, by blocking the virus’s
ability to activate TAM receptors, leaving theinterferon-mediated antiviral response intact insuch viruses as West Nile, dengue, influenza,
Ebola, Marburg and hepatitis B. This is acompletely novel approach, says Young, andif it works, it may prove effective at clearing
enveloped viruses during the acute phase of
infection and perhaps in chronic viral infections
as well.

Inside Salk 1 | 14 Discovery Roundup

27

Discovery Roundup

From left: Scientists John Reynolds, Anirvan Nandy and Tatyana Sharpee

Scientists help explain visual system’s remarkableability to recognize complex objects
HOW CAN A HUMAN EYE FIGURE OUT
twisted and looped letters, like those in thelittle security tests Internet users are often
given on websites? The task is so complex,
no one has been able to write computer codethat translates these distorted letters thesame way that neural networks can. That’s
why the test is used to distinguish a human
response from computer bots that try to steal
sensitive information.
Two studies by Tatyana Sharpee andJohn Reynolds published in Neuron and theProceedings of the National Academy of
Sciences (PNAS), have demonstrated how
complex a visual task decoding the test or any
image made of simple and intricate elements
actually is to the brain. Sharpee and Reynolds
sought to figure out how a part of the visualcortex known as area V4 is able to distinguish

28

Discovery Roundup Inside Salk 1 | 14

between different visual stimuli even as thestimuli move around in space.
“Neurons in the visual system are sensitive
to regions of space—they are like little windows
into the world,” says Reynolds. In the earliest
stages of processing, these windows, known as
receptive fields, are small, with access only to
information within a restricted region of space.
Neurons in V4 have a larger receptive fieldthat can also compute more complex shapes,
such as contours.
Both studies investigated the ability of aneuron to recognize the same stimulus within
its receptive field no matter where it is in space,or where it happens to fall within the receptive
field. The researchers found that neurons that
respond to more complicated shapes need thatcomplicated curve to be in a more restricted
range for them to detect it and understand its

meaning. On the other hand, neurons in V4
tuned to recognize simpler shapes don’t care
where the stimulus they are tuned to is as longas it is within their receptive field.
The results indicate that there is a deeper
mystery to be solved, Reynolds says. “What wehave done is unpack part of the machinery forachieving integration of parts into wholes.”“Neurons in the visualsystem are sensitive toregions of space—they
are like little windows
into the world.
– JOHN REYNOLDS”

www.salk.edu

From left: Scientists Ludovic Mure, Megumi Hirota and Satchin Panda in Salk’s Regulatory Biology Laboratory.

Drug blocks light sensors in eye that may trigger migraine attacks
SCIENTISTS HAVE KNOWN FOR NEARLY A CENTURY THAT HUMANS
and animals can sense light even when they can’t see, and more than ten
years ago, Satchidananda Panda’s lab discovered that melanopsin, a
receptor found in neurons connecting the eyes and brain, is responsible
for sensing light independently of normal vision. Since then, researchers
have determined that the receptor is vital for maintaining sleep cycles
and other circadian rhythms in those with healthy vision, constricting
the pupil of the eye in bright light and potentially exacerbating thelight-sensitivity associated with migraines. While melanopsin senses lightfor these non-vision purposes, closely related receptors—rhodopsin andcone opsins—provide vision-forming information to the brain.
In a recent study published in Nature Chemical Biology, Panda reported
that a new molecule that selectively blocks light-sensitive receptors in theeyes could help people with migraines or circadian rhythm imbalances
without affecting normal vision.
Scientists already know of one class of compounds, retinoids, whichinteract with opsins, but they are non-specific and bind to melanopsin,rhodopsin and a handful of other receptors in the body, causing widespreadwww.salk.edu

side effects. Panda wanted something more specific, so for ten years,
his group, in collaboration with scientists at the pharmaceutical company
Lundbeck, has attempted to find chemical compounds that specificallyshut off melanopsin in animals.
In their latest search, Panda and his collaborators turned to Lundbeck’s
library of compounds. A team at Lundbeck tested whether each chemicalfrom the library turned off melanopsin; several appeared to block its function. None looked like retinoids, and the chemicals, dubbed opsinamides,
also showed no interaction with rhodopsin or other opsins. To make surethey were specific to melanopsin and to determine whether they would
have a physiological response in addition to binding to melanopsin, Panda’s group next looked at whether the drugs affected pupillary constriction
in mice. The results showed that the drugs stop melanopsin from signaling
the brain when the eyes are exposed to bright light.
The compounds require further optimization in anticipation ofclinical testing but are extraordinarily useful for research and as leads inthe discovery process.

Inside Salk 1 | 14 Discovery Roundup

29

The nextgeneration:

Fear Factor!
Kevin Curran puts fear
under the microscope andchallenges notions of what
it means to be afraid

30

Next Generation Inside Salk 1 | 14

www.salk.edu

F

OR A MAN WHO STUDIES FEAR FOR A LIVING,
Kevin Curran exhibits little of it in his everyday life.
The moment he leaves his work at Sreekanth Chalasani’s
Molecular Neurobiology Laboratory at the Salk, he’s
likely sailing the open ocean, scuba diving or spearfishing. With a wide grin, the postdoctoral researcher readily admits,“I’m an outdoorsy person.”
Inside the lab, however, Curran throws himself into challenges
of a different kind. “Kevin chose a project that was difficult,”
Chalasani says, “but in a short time has made a ton of progress.
In fact, we are currently writing up the results for what should bea very exciting publication.”
The project that Curran adopted is identifying specific molecular pathways that modulate threat avoidance behavior, using
Caenorhabditis elegans, a nematode, for his subject. Serotoninsignaling is markedly well conserved between C. elegans andHomo sapiens, making it an ideal candidate for focused research.
While previous studies acknowledge the link between serotonin
circuitry and fear/anxiety behavior, less is known about how
serotonin actually modulates neural circuits. This is what Curran
is working diligently to identify.
His research has very real application for humans. While theability to respond appropriately to a potentially harmful situationis critical to an organism’s well-being, the behavior can go awry.
In humans, for example, malfunctions in this neurobiologicalprocess can lead to such debilitating diseases as panic attacks
and post-traumatic stress disorder, conditions becoming evermore prevalent in today’s fast-paced and competitive society. It’s
estimated that the cost of treating anxiety disorders in the U.S.
exceeds $42 billion a year.
“Actual fear has a tangible stimulant: a person sees something
threatening, and the body has an appropriate response, often
characterized as fight or flight,” Curran explains. “Anxiety, on
the other hand, does not have a tangible stimulant, but the bodyreacts in a similarly heightened manner.”
Outward symptoms such as shortness of breath, palpitations
and dizziness often lead to insomnia, fatigue and physiologicalstress across multiple organ systems. “We are seeking to learn
which novel pathways are active in C. elegans during avoidance
behaviors and which chemicals affect those behaviors, with thegoal of duplicating our findings in mammalian species.”
The research so far has produced some very interesting results,
says Chalasani. “In lab experiments we often forget how animals
live in the natural world, the challenges they face and thestrategies they use to survive and reproduce,” he says. “Kevin’s
unique insights have changed the way we approach this project
and are instrumental in us studying some very fundamental
behavior. His project is one of the first to show that worms might
have a rudimentary form of a very complex (likely emotional)
fear-like behavior.”

www.salk.edu

Inside Salk 1 | 14 Next Generation

31

“[Kevin’s] project is
one of the first toshow that worms might
have a rudimentary
form of a very complex(likely emotional)
fear-like behavior.
– SREEKANTH CHALASANI

32

Next Generation Inside Salk 1 | 14”

In May, Curran was the recipient of the
Alumni-Faculty Fellowship, an award that will
enable him to conduct a drug screen to further
identify which molecular pathways modulate
threat avoidance behavior.
Out in the natural world, Curran tests his own
ability to respond appropriately to potentiallyharmful situations again and again, especiallyon the ocean. While completing his Ph.D. at the
University of Washington, he took sailing lessons
and upon completion, bought a 30-foot keel hull
sailboat named Alizé, French for “trade wind.”
As a personal challenge, he set out on a fourmonth journey exploring the Alaskan coastline.
“I didn’t have a job lined up, so whenever I
landed in a port with an Internet café, I’d checkthe job listings,” he says. “Eventually I cameacross one for Dr. Chalasani’s lab. I knew himfrom a presentation he’d given when I was a gradstudent. His talk was awesome! So I applied forthe position. Luckily, Dr. Chalasani remembered
me too and invited me down.”

With the winds having landed him at the
Salk Institute, Curran now lives aboard his
sailboat in the San Diego harbor. “It’s a wholemix of people living on my dock,” he says. “Ilike the fact that they’re from all walks of life;
the unifying thread is that we all love boats.”
After his usual early morning run, it’s off
to the lab, where Curran enjoys a vibrant andproductive working relationship with “Shrek,”
as Chalasani is affectionately known. “He
has an amazing capacity to generate ideas,”
Curran says of his mentor. “His enthusiasm
never wanes.”
When work is finished and the setting
sun is polishing the marina’s gleaming whitehulls, Curran eagerly returns to the ocean. And
while others are stopping at the store to pickup something for dinner, Curran is donning
his wetsuit and diving into his own grocery. “Ispearfish for sheepshead, kelp bass, rockfish,”he says. “In season, I catch California spiny
lobsters with a couple of the other guys here.”
Delivering his trademark grin that knows nofear, he says, “It’s a good life!”

www.salk.edu

Salk Science Leads to Discoveries.

IMPACTING HUMAN HEALTH BEGINS AT THE SALK.

Scientific discovery at the Salk Institute is made possible through annual
contributions from individuals, organizations, corporations and foundations.
Your support will accelerate the pace of breakthroughs in understanding
disease and pave the way to new drug therapies. To learn more, please
visit www.salk.edu/support or call 858.453.4100 x1405.

Get Involved
FRIENDS OF SALK
Unrestricted gifts, in any amount, provide funding where it is most needed and allow our scientists to conduct critical
early-stage research. Contributors up to $2,500 receive Inside Salk magazine and invitations to annual events.
SALKEXCELLERATORSThe Salkexcellerators program is focused on making Salk science accessible to a younger generation of businessprofessionals, entrepreneurs, and volunteers. Donors receive Inside Salk magazine and invitations to private receptions
and lectures with Salk’s renowned scientists. Salkexcellerators meet in La Jolla and New York City, and engagement ranges
from $500 to $5,000.
PRESIDENT’S CLUBPresident’s Club donors fulfill a central role for the Institute and provide the flexibility to respond to Salk’s greatest needs.
Contributors of $2,500 – $25,000 enjoy unique opportunities to interact with our scientists in the lab and receive
Salk publications.
CHAIRMAN’S CIRCLE
Chairman’s Circle visionary donors support the Institute’s mission with unrestricted annual gifts of $25,000 andabove. Their generous support fills a vital need for the Institute by providing the world’s finest minds in science withthe resources to pursue discoveries at the frontier of human knowledge. Donors are invited to exclusive lab tours andspecial events with senior researchers that provide opportunities to discuss specific areas of interest. Donors receive
Salk publications and individual reports on the impact of their gifts.
SPECIAL PROJECTS
If you have a special interest in one of Salk’s areas of research, such as cancer, aging, diabetes, neuroscience, genetics,
vision or plant biology, you may designate your gift to support investigations in that field. You may also elect to support thework of a young scientist with a fellowship or Salk’s education outreach programs. You will be privy to exclusive updates
and invitations.
PARTNERS IN RESEARCH
Salk’s legacy society, Partners in Research, welcomes those who have included Salk in their estate plans. Charitable giftplanning is a powerful way of ensuring your legacy lives on, and it can maximize tax and other financial benefits to you,your family, and the Institute. Partners in Research members receive special communications and are invited to events
throughout the year.

www.salk.edu

Inside Salk 1 | 14 Philanthropy

65

Clodagh O’Shea

Ursula Bellugi

Women & Science events entertain and inspire
THE SALK INSTITUTE’S WOMEN & SCIENCE

Beverly Emerson, holder of the Edwin K. Huntertumor cells before bursting them apart to releaseprogram continues to attract an ever-growing

Chair in the Regulatory Biology Laboratory,

thousands of viral progeny. These progeny thenaudience, and in recent months presented two

described the iconoclastic O’Shea as a crossseek out and destroy distant metastases while

thought-provoking events.

between Grace Kelly, bareknuckle boxer John

overcoming all possible resistance.
The 2013 Women & Science outreach events

On July 23, Ursula Bellugi, professor and

Sullivan and risk-taking adventurer Edmund

director of the Laboratory for Cognitive Neuro-

Hillary. O’Shea embodied all three as she

have been generously underwritten by Union

science, gave a talk titled “Williams Syndrome:

spoke passionately of her search for a sophisti-

Bank and by the wealth advisory firm Hoyle-

A Model for Linking Genes, Neural Systems andcated anticancer tool that could target tumors

Cohen. For more information on the Women &Social Phenotypes.” Following an introduction

without causing the bodily harm of current

Science program, contact Betsy Reis, director of

by Catherine Rivier, professor emerita of thecancer treatments. In her talk, titled “Designing

donor relations, at 858.453.4100 x1426 or by

Clayton Foundation Laboratories for Peptide

Viruses that Seek and Destroy Tumor Cells,”

email at breis@salk.edu

Biology, Bellugi explained to a crowd of approxi-

O’Shea explained how she and her lab are using

mately 60 female business and community

the common cold virus, the adenovirus, toleaders how she works with individuals withcreate synthetic viruses that can act like guided

Williams syndrome to further understand themissiles, specifically infecting and replicating inties between neural and cognitive functions.
Those with this rare genetic disorder, though

From left to right: Ursula Bellugi, Ph.D., Diana Vines, Pamela Ombres

developmentally disabled, possess remarkableverbal abilities and facial recognition skills.
Because the genetic deletion is so tiny—of the
20 or so genes missing, just three to six create
the cognitive and social effects typical of
the condition—Bellugi and her colleagues are
beginning to identify the very genes and neuralpathways that help determine language andsocial skills.
Then, on November 6, a crowd of more than
80 gathered to hear Clodagh O’Shea speak
about her work designing synthetic viruses
to combat cancer. During her introduction,

66

Philanthropy Inside Salk 1 | 14

www.salk.edu

Back to Basics: Spicing up Alzheimer’s drug discovery» Webextra: To view the video
wwww.salk.edu/jan14/video1/
Marguerite Prior

SALK SUPPORTERS GATHERED ON OCTOBER 2 FOR THE

grown in laboratory dishes to test new synthetic compounds forlatest Back to Basics lecture. Titled “Spicing up Alzheimer’s Drugeffectiveness at protecting brain cells.

Discovery,” it featured Marguerite Prior, a research associate in the
Cellular Neurobiology Laboratory of David Schubert.
In her talk, Prior described how the cognitive decline thatcharacterizes Alzheimer’s disease results from the progressive lossof nerve cells in areas of the brain and how Schubert’s lab has
developed a novel drug discovery scheme that uses living neurons

Using this strategy, Schubert’s team has identified a potent
compound, J147, that shows strong therapeutic potential for
Alzheimer’s by slowing the disease’s progression and rapidly
improving memory.
The audience was riveted throughout Prior’s presentation,
and an animated question and answer session followed.

Prior discusses her research with a Back to Basics attendee.

www.salk.edu

Inside Salk 1 | 14 Philanthropy

67salk cellkeep up with cutting-edge science

Salkexcellerators are professionals from varied sectors in San Diego and New York City who share a commitment to supporting scientificdiscovery at the Salk Institute. Members receive invitations to social events throughout the year featuring talks by Salk scientists about someof the most critical health-related issues of our time. Through their support, the Salkexcellerators fund an annual fellowship for talented
postdoctoral scholars, like Jonathan Nassi, Ph.D., this year’s fellowship recipient.
Two recent events brought together members for thought-provoking evenings with three of the Institute’s most innovative faculty, who
presented their latest findings.

On October 30, the New York Salkexcellerators gathered at the private Norwood Club in Chelsea for a special evening with Reuben Shaw, an associate
professor in Salk’s Molecular and Cell Biology Laboratory. In his talk, “Cancers Are Addicted to Sugar: Targeting Their Demise with Metabolism Drugs,”
Shaw shared findings from his lab that could lead to new treatments for cancer using existing diabetes drugs.

Reuben Shaw and New York Salkexcellerators Mark Herschberg and Mitzie Perdue

68

Philanthropy Inside Salk 1 | 14

www.salk.edu

Salkexcellerators from left to right: George and Greg Katakalidis, Michael and Devra Doiron, Mary Katakalidis

The San Diego Salkexcellerators gathered at the Institute November 13 to hear Janelle Ayres, an assistant professor in the Nomis Foundation Laboratories
for Immunobiology and Microbial Pathogenesis, and Satchidananda Panda, an associate professor in the Regulatory Biology Laboratory, speak about two
different aspects of diet and health. The evening’s program, “Metabolism and Microbial Balance,” highlighted discoveries that have changed our thinking
about combating disease through eating patterns and stabilizing our immune response with healthy bacteria.
San Diego Salkexcellerators

For more information about joining the Salkexcellerators at events like these year round, contact Megan Shockro at 858-453-4100, ext. 1405,
or visit www.salk.edu/salkexcellerators.
www.salk.edu

Inside Salk 1 | 14 Philanthropy

69

THE SALK INSTITUTE WAS STRONGLY REPRESENTED
in the first annual Pedal the Cause San Diego—a weekend
cycling event that took place October 26 and 27 to benefit
San Diego’s three cancer centers: the Salk, UC San Diego’s
Moores Cancer Center and the Sanford-Burnham Medical
Research Institute. In addition to helping strengthen the bonds
between the cancer centers on the Torrey Pines Mesa, the Salk
Cancer Center team raised more than $18,000 for research.
The Institute is most grateful to everyone who invested incancer discovery by sponsoring Team SCC.

Team Salk Cancer Center, from left: Henry Juguilon, Mara Sherman, Nicholas White, Michael Sullivan, Maryam Ahmadian, John Reynolds, Sam Pfaff, John Young, Geoff Wahl, Tony Hunter, Mathew Lewsey, Kevin Waldrop

70

Philanthropy Inside Salk 1 | 14

www.salk.edu

William R. Brody, M.D., Ph.D.
President, Salk Institute
Irwin M. Jacobs Presidential Chairwww.salk.edu

YEARS AGO, STANFORD PHYSICIAN DR. JAMES FRIES PROPOSED AN IDEA WHICH HAS
been deemed the “compression of illness” hypothesis. According to Fries, the best strategy bothfor healthy living and lowering medical costs is to delay the time of onset of chronic disease: inother words, slow down the appearance and progression of chronic illness.
When Fries proposed this idea, it was highly controversial. Critics of the strategy suggested
that if chronic illness appeared early, longevity would be shortened and overall healthcare costs
would be lower, even though the outcome would be worse for the individual patient. In otherwords, the healthcare costs of dying of a heart attack at age 40 might be lower than living to age
75 with heart failure that occurs at age 65.
Yogi Berra supposedly once said: “In theory there is no difference between theory andpractice. In practice, there is!” In this case, subsequent studies appear to validate Fries’s theory.
Interventions that slow or delay the onset of a chronic illness appear to lead to lower overall
healthcare costs incurred by that patient. Of course, addressing the costs of treating chronic
illness is still an enormous challenge—one that has become a major concern in recent decades.
Unfortunately, chronic illness requires chronic treatment.
Today, formerly acute illnesses, including infection, heart disease and many forms of cancer,
have been transformed by medical science into chronic diseases. According to some estimates,
Medicare patients with five or more chronic illnesses consume 75 percent of the costs of thisimportant federal program. Common logic dictates that bending the cost curve requires morecost-efficient methods of care for arthritis, heart disease, cancer, stroke, depression, dementia,
Parkinson’s disease and other chronic illnesses.
The Salk Institute has a lot to offer in addressing this issue. As the feature article on theCampaign for Salk’s Healthy Aging Initiative in this issue of Inside Salk explains, deciphering
how cells change at the molecular level as we get older will help us bolster our ability to fend
off age-related illnesses. Similarly, our Genomic Medicine Initiative was also designed totackle chronic illnesses that undermine our health as we age. The Helmsley Center for Genomic
Medicine, established by the largest gift in the Institute’s history, has at its core the focus onunderstanding chronic inflammation and the role that our immune system plays in aging and thedevelopment of chronic disease.
Salk scientists believe that there is a common thread to chronic illness and the aging process:chronic, low-grade inflammation. When our body encounters something it considers ‘foreign,’
like a bacterium, it sends signals to the genome of immune cells that participate in fighting theforeign invader. Unfortunately, as Salk scientists are discovering, sometimes what gets turned on
fails to get fully turned off, which can lead to so-called autoimmune diseases, like rheumatoid
arthritis and type I diabetes. In addition, there may be other forms of chronic inflammation thatkeep the immune system activated, albeit at a lower level, and this form of chronic immune
response may play a previously undiscovered role in chronic illness as well as the aging process.
Finding the keys to chronic illness will reduce the burden of healthcare costs and at the sametime help us stay healthy longer. By ‘compressing’ illness, Salk science helps people live theirlives to the fullest.

Inside Salk 1 | 14 Insider’s View

71

NONPROFIT ORG.
U.S. POSTAGE

PA I D

10010 N Torrey Pines Rd
La Jolla, California 92037-1002

PERMIT NO. 611
SAN DIEGO, CA

Telephone: 858.453.4100
Fax: 858.552.8285
www.salk.edu

There are many ways to support Salk. For detailed information on opportunities, please email giving@salk.edu or call 858.550.0472

Salk Calendar
JANUARY
22 The Art and Science of Cuisine
26 Salk Science & Music Series
FEBRUARY
13 Partners in Research Luncheon
23 Salk Science & Music Series
26 San Diego Salkexcellerators
MARCH
16		 Salk Science & Music Series
18 Women & Science Reception
25 Back to Basics
26 San Diego Salkexcellerators
APRIL
12		 Second Annual Step into Discovery

will take place at the Institute on

Wednesday, January 22, 2014.
For more information visit the website at www.salk.edu/cuisine/BE
INSPIRED!

Follow us on:

facebook.com/salkinstitute

The Art and Science of Cuisine

twitter.com/salkinstitute