The Simons Foundation 2008 Annual Report

Annual Report 2008

The figures on the cover are projections into the plane of n-dimensional hypercubes (aka n-cubes), as n var-ies from zero to eight – eight to coincide with the year of the annual report, 2008. The projections are orthog-onal projections chosen in such a way that the convex hull of the n-cube projection is a regular 2n-gon in the plane, called the Petrie polygon of the projection. Since the n-cube is a face of the (n+1)-cube, the projections are linked in a natural way: the vertices that make up each projection's convex hull can be seen in the pro-jection of the next higher-dimensional cube. Thus, the red polygon highlighted in each figure is the image of the Petrie polygon of the next lower-dimensional cube, helping the viewer to grasp the relationships between the n-cubes.

President’s Message

Math & Science

SFARI

Financials

Simons Staff

Simons Grants

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Contents

In today’s complex, deeply specialized, and vast world of research possibilities, how does the Simons Foundation envision having an impact? We see our potential to advance research through grantmaking that encourages collaborations, makes con-nections, and builds bridges. We seek to fund studies that will heighten interchanges between institutions, across fields, and among scientists to facilitate the exchange of new ideas. A few examples of grants made this fiscal year will illustrate our funding strategies and goals.

Modern theoretical physics and the geometric aspects of mathematics have had increasingly fruitful interactions in the past 30 years, illuminating and advancing both fields. We have every reason to expect that this approach will continue to be produc-tive. To this end, the Simons Foundation is funding the Simons Center for Geometry and Physics in order to bring together mathematicians and physicists investigating the fundamental shape and structure of the universe.

The application of quantitative methods to biology has been progressively more productive over the past several decades. The use of statistical methods and large-scale data analyses, for example, is in the process of revolutionizing modern genet-ics. The applications of both math and physics have been critical to neurobiology. Bringing together mathematicians and biologists, the Simons Foundation supports a Biology Colloquium at the Mathematical Sciences Research Institute (MSRI), a systems biology program at the Institute for Advanced Study (IAS), and a newly established biology program at the Institut des Hautes Études Scientifiques (IHÉS). Through these interdisciplinary programs, the foundation hopes to stimulate col-laborations that will further advance research in the life sciences.

Letter from the President“Collaboration can lead to new ways of looking at old problems; partnerships can lead to a synthesis of ideas; teamwork can help us build something greater than ourselves.”

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Connecting investigators and facilitating their joint efforts to build a repository of blood samples and a collection of psychological assessment data is the goal of the Simons Simplex Collection (SSC). This project, involving over 100 people work-ing in research teams at 13 outstanding institutions, is compiling a large sample of genotypic and phenotypic information to be made available for research worldwide. By coming together to assure a uniform standard of excellence, it is hoped that scientists will further our understanding of the fundamental roots of autism.

These grants are important representatives of our key strategy of building bridges. Collaboration can lead to new ways of looking at old problems; partner-ships can lead to a synthesis of ideas; teamwork can help us build something greater than ourselves. By working together we anticipate exciting developments in the years ahead.

The Foundation is pleased to support many excellent projects. I hope you will enjoy reading about our work.

Sincerely,

Marilyn SimonsPresidentSimons Foundation

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Progress through Math and Science

Simons Foundation Annual Report 2008 { Math & Science }4

The Flower of Maths What is a mathematician? Not a scientistNot an artistBut caught between the twoIn a world of structures and truthsCreating the seeds But proving the flowersAnd vaguely hoping That their scent will save the world

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– Wendy Lowen

6 Simons Foundation Annual Report 2008 { Math & Science }

From the work of Archimedes on the center of mass to that of Einstein on the shape of the universe, there has been crucial interdependence between theoretical phys-ics and the geometric side of mathematics. Recent devel-opments in cosmology, string theory and quantum field theory, together with important progress in topology and differential geometry, have caused these fields to become increasingly intertwined, as developments on each side stimulate and inform developments on the other.

At the Simons Center for Geometry and Physics at Stony Brook University, researchers will explore these interactions, hopefully deepening their understanding of each field in its own right and continuing to unravel their remarkable relationship to each other. The building housing the center is scheduled to open in 2010.

“Mathematicians often develop their mathematical con-cepts based on internal consistency, elegance and appropriate generality, independent of these physical connections,” said Dennis Sullivan, professor of mathe-matics at Stony Brook, National Medal of Science recipi-ent, and trustee of the new center. “Physical models

present mathematicians with a remarkable opportu-nity to develop new mathematics. Environments that encourage younger generations of mathematicians to become aware of this physical intuition and these poten-tial worlds of mathematics are welcome and timely.”

The Simons Center will give mathematicians and physicists the opportunity to work in an environment and architecture designed to enhance collaboration. In addition to providing an attractive facility, the gift will be used to recruit and retain permanent faculty, provide enhanced training and support for graduate students, attract visiting scholars and post-docs – up to 30 at a time – and sponsor workshops and conferences. John Morgan, known for his contributions to topology and geometry, and formerly chair of the Mathematics Department at Columbia University, will be the center’s first director. Among the permanent faculty members of the center will be internationally renowned string theorist Michael R. Douglas. Dr. Douglas was instrumental in the development of the first solvable models of string theory and its relations to particle physics and mathematics.

Simons Center for Geometry and Physics

“The Simons Center will give mathematicians and physicists the opportunity to work in an environment and architecture designed to enhance collaboration.”

Left: Rendering of the new Simons Center for Geometry and Physics.

Right: Dr. Morgan, a mathematician known for his contributions to topology and geometry, is the Simons Center's first director.

www.scgp.stonybrook.edu

– Jim Simons

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Why is it important to have a center for both geom-etry and physics under the same roof?

Around the world there are many centers for geometry and centers for physics. Sometimes, like for example at the Institute for Advanced Study, they exist side by side in the same place, but even when they exist in the same place there is usually little organized interac-tion between the groups. What we are attempting to do here is to create an environment in which geom-eters and physicists can exchange ideas in a way that enriches both disciplines. The recent interaction has its origin in conversations between Jim Simons and C.N. Yang, here at Stony Brook in the 1960s, concerning the latest developments in physics, gauge theories, and the corresponding mathematical context. But as physics of gauge theories developed and string theory came along, the developments in physics outstripped the available geometry. While these developments give hints about the nature of the geometry that would be needed, what is needed is far too vast, new and different to be devel-oped full-blown out of the hints so far provided by phys-ics. What the nature of this geometry is and how it will be useful in physics are fundamental mysteries in both subjects. Progress toward their resolution will surely have major impacts, some indication of which we can already see. Studying these mysteries – from the math-ematical perspective, the physical perspective and the joint perspective – is the focus of the Simons Center for Geometry and Physics.

How will the center create an atmosphere where sci-entists from both disciplines can collaborate?

We hope to create the collaborative atmosphere in sev-eral ways. First of all, the building will have much open, common space with blackboards, chairs and tables to facilitate spontaneous, scientific conversations. As we search for permanent members, post-docs and visitors, we will put real emphasis on a desire for collaboration across the math-physics divide. On the programmatic

level, we will be running workshops where the topics will be of interest to both geometers and physicists.

What are some areas of research interest that the center will focus on?

There are many topics that I could list, but I will list the topics of this year’s workshops. The titles of the three workshops planned for the spring are ‘Derived Geometry’, ‘Kahler Geometry and Extemal Metrics’, and ‘String Field Theory’. As the first two names indi-cate, these topics fit squarely in the area of geometry, but there is a modern twist in the topic inspired by physics, and in particular by string theory, which is one of the most active areas in theoretic high-energy physics. In the study of string theory, the appropriate geometry is not the classical geometry of Gauss and Riemann alluded to before, but rather a more abstract form of geometry ‘derived’ from these classical forms. Ideas from string theory have led to new insights into and new questions about these derived geometries and their relation to classical geometry. These insights have already produced a revolution in how we think about ‘classical geometry’, and there promises to be much more to come. This geometric revolution is providing new impetus for progress in physics. The topic of the last workshop this year is one that belongs more purely to physics: the study of modern string theory.

For interviews with John Morgan and Dennis Sullivan visit www.simonsfoundation.org.

Interview with John Morgan Director of the Simons Center for Geometry and Physics

“What we are attempting to do here is to create an environment in which geometers and physicists can exchange ideas in a way that enriches both disciplines.”

Zach Korzyk’s biggest challenge teaching math at a New York City public school is keeping his students motivated.

“Some students don't like that I won't let them be pas-sive in class and do poorly,” said Korzyk. “I make them take notes and answer questions. The upper-level students are grateful for challenging problems and engaging conversations.”

Korzyk, 24, has been teaching math since 2007 as a fellow in the Math for America (MƒA) program. He’s one of about 200 teachers MƒA has recruited to help address a critical shortage of qualified math teachers. Nearly 40 percent of all public high-school math teach-ers do not have a degree in math or a related field, according to one study.

As an undergraduate at Boston College, Korzyk majored in theatre arts and computer science, with a minor in mathematics. He wanted to teach math but wasn’t sure how he could get a job without a degree in teaching. Then, he spotted an advertisement for

MƒA. After joining the program, MƒA sent him to Bard College for a master’s degree in teaching with a con-centration in secondary mathematics.

Korzyk is about halfway through his five-year commit-ment to MƒA, and while it’s a tough job, he said he loves his work.

“I really enjoy coming up with interesting activities that pleasantly surprise my students,” Korzyk said. “I like to encourage them and see them grow mathematically.”

MƒA was launched in 2004 to address the deficit in math education. To date, the program has recruited, trained and retained more than 200 skilled mathemati-cians to work as teachers in New York City’s public schools.

Building on this success, MƒA is expanding to other cities around the country. The nonprofit has created a national office while starting new programs in San Diego, Los Angeles and Washington, DC.

Math for AmericaThe program has recruited, trained and retained more than 200 skilled mathematicians to work as teachers.


“The ultimate goal of MƒA programs is to convince people that our approach to recruit and retain outstanding teachers works and our underlying principles can dramatically improve mathematics education across the country.”

To further its expansion, MƒA seeks partnerships with state governments, educational institutions and foun-dations. Leading the expansion is MƒA’s new presi-dent, John Ewing, the former head of the American Mathematical Society.

“The ultimate goal of MƒA programs is to convince peo-ple that our approach to recruit and retain outstanding teachers works and our underlying principles can dra-matically improve mathematics education across the country,” Ewing said.

For gifted mathematicians who are new to teaching, MƒA offers its five-year fellowship. Following a rigor-ous selection process, fellows spend a year earning a master’s degree in mathematics education with a partner college or university. Fellows then teach for four years in New York City’s public schools. The fellowship includes a full tuition scholarship with a stipend of $100,000 over five years to supplement their teacher’s salary. The program includes mentoring, leadership opportunities and professional development services.

Exceptional high-school math teachers currently work-ing in public schools are recruited into the four-year Master Teacher program. Teachers receive annual stipends and participate in professional development and leadership opportunities.

For Korzyk, the experience of teaching with MƒA and being part of a corps of other math-savvy individuals has taught him lessons that he applies every day on the job.

“I’ve learned to maintain high but clear expectations for my students,” he said. “I am getting better at explaining assignments in different ways so my students at every learning level know what to do.”

www.mathforamerica.org

– John Ewing

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Heart attacks, known to doctors as myocardial infarc-tions, are a leading cause of death around the world.

At the Institut des Hautes Études Scientifiques (IHÉS), a research team led by Mikhail Gromov is seeking to use mathematics to better understand the cause of heart attacks.

The Simons Foundation supports Gromov’s investiga-tion of the heart as part of its 11-year record of contri-butions to IHÉS. Half of a recent contribution from the Simons Foundation will fund the Institute’s activities at the interface of biology and mathematics.

The investigation into the electrophysiological geometry of the heart by Gromov continues the Institute’s tradi-tion of fundamental research in the sciences. Gromov’s team hopes that the knowledge they will gain through their investigation will help in discovering ways to prevent heart attacks.The objective is to identify a metric that governs the propagation of electromagnetic waves in the heart. The metric may prove useful in characterizing normal and abnormal heart functions.

IHÉS is one of the world’s premiere research institutions. Located in Bures-sur-Yvette, France, IHÉS is dedicated to fostering fundamental advances in mathematics, physics and other related theory-based disciplines.

Founded in 1958, IHÉS has a small number of perma-nent professors, appointed for life, and invites about 200 visitors a year for varying terms averaging three months. It also has a small number of long-term visi-tors. Research is not contracted or directed: it is left to each individual researcher to pursue their own goals. Permanent professors are only required to be in resi-dence six months a year.

www.ihes.fr

Institut des Hautes Études ScientifiquesGromov’s team hopes that the knowledge they will gain through their investigation could help in discovering ways to prevent heart attacks.

Left: Mikhail Gromov.

Right: Dennis Sullivan and Mikhail Gromov.


Top: Image of an electrocardiogram.

Left: Maxim Kontsevich.

Right: Alain Connes.

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Michael Atiyah is sometimes described as one of the greatest living mathematicians. He was the corecipient, along with Isadore Singer, of the Abel Prize, an award that is compared to the Nobel Prize. The prize was awarded for their development of the Atiyah-Singer Index Theorem that is used to count the number of independent solutions of many important differential equations.

In honor of Atiyah’s achievements, the Simons Foundation has established the Michael Atiyah Chair in Mathematical Sciences at the American University of Beirut (AUB).

The gift will be used to attract top researchers and professors to the university. AUB’s Faculty of Arts and Sciences Dean Khalil Bitar noted that the endowment would bring new possibilities to the study of mathemat-ics at the university.

“The recent surge in the use of mathematical tech-niques via computer simulations in fields that tradition-ally have not made use of mathematical analysis and/or

mathematical modeling will be greatly enhanced with leadership in this chair in the mathematical sciences,” Bitar said.

Atiyah has spoken passionately about the importance of mathematics. During a speech at AUB, he described mathematics as “an essential component of our world. In all the sciences, physical, biological or social, math-ematics is increasingly important, and in recent years the business and financial community has also woken up to this fact.” When he was awarded an honorary doctorate from AUB in 2004, Atiyah described himself as “a firm believer in the fundamental and central role that mathematics plays in our modern technological society, where it underpins everything from science and engineering to finance and economics.”

The Simons Foundation hopes that the gift will help the university excel in both academic research and out-standing pedagogy.

“For many years AUB has been a beacon of scholarship and tolerance in an embattled part of the world,” said

American University of Beirut“In the broad light of day mathematicians check their equations and their proofs, leaving no stone unturned in their search for rigour. But, at night, under the full moon, they dream, they float among the stars...”

Jim Simons. “We are pleased to think that our contribu-tion will help and strengthen the university in continuing to fulfill this important mission.”

www.aub.edu.lb

College Hall, the main building at the American University of Beirut.


Of the hundred of types of cancers that can afflict the human body, brain cancer poses some of the toughest treatment challenges. Getting drugs into the brain can be difficult because a barrier physically shields the brain from chemicals circulating in the body. Medications that do enter the brain may cause serious side effects.

Memorial Sloan-Kettering Cancer Center’s new Brain Tumor Center (BTC) is working to overcome these obstacles using recently revealed insights into the molecular and cellular properties of tumors. Scientists are trying to create therapies that target cancer cells and the abnormal signaling pathways needed to main-tain them.

The Simons Foundation supports this important work by underwriting preclinical studies of new therapies for the type of tumors called gliomas to confirm that they produce their desired effect in animal models. There currently exists no drug pipeline developed specifically for gliomas, and such preclinical work is an essential step in the design of new therapies for use in humans.

The BTC is undertaking both basic scientific investiga-tions into brain tumors and translational research in which potential new targets and therapies make the transition from animal experiments to humans.

One major goal at BTC is to find chemicals that can be used in glioma treatment. In a gleaming room in Memorial Sloan-Kettering’s new research tower on Manhattan’s Upper East Side, the arms of a robotic laboratory click and whirr. Machines are testing 250,000 compounds to see if they might be useful in killing tumor cells. The screening machines have found several compounds that enhance the ability of radiation

to kill cancer cells, specifically block cell proliferation, inhibit development of specific stem cells and prevent cancer cell survival.

“These machines can screen compounds thousands of times faster than we could in the past,” said Hakim Djaballah, the director of the high-throughput screening core facility.

BTC director Dr. Eric Holland has developed a prom-ising new system for glioma modeling. Holland’s col-league, neurosurgeon Philip Gutin, and Shahin Rafii, a hematologist at Weill Cornell Medical College, are seeking to treat tumors by cutting off their blood supply. The team is studying the use of blood supply-produc-ing cells derived from bone marrow.

Research into brain tumors may also be useful in understanding autism. Of the several candidate genes that enhance the risk for autism uncovered so far, three – PTEN, TSC1 and TSC2 – are part of biochemi-cal pathways that suppress the formation of tumors. Disabling these genes in mice produces signs and symptoms that are relevant to autism in humans.

“Putting Memorial Sloan-Kettering’s basic science peo-ple together with neurosurgeons and medical oncolo-gists and radiation oncologists – everyone who treats brain tumors – facilitates the exchange of ideas among investigators with conjoined interests,” said Dr. Holland.

www.mskcc.org

Memorial Sloan-Kettering Cancer CenterScientists are trying to create therapies that target cancer cells and the abnormal signaling pathways needed to maintain them.

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SFARI: Simons Foundation Autism Research Initiative

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“We are not alone in the effort to understand autism. This effort goes to the core of the human condition, so one can expect that real advances will take the combined efforts of a world wide community of scientists of all stripes.”

– Gerald D. Fischbach

An important goal of SFARI is to create tools that scientists can use to enhance our understanding of autism. Last fall, we released the first set of phenotype data and DNA from the SFARI Simplex Collection (SSC). The SSC is a tool of fundamental importance that will facilitate the identification of autism genetic risk factors. Studying alterations in gene structure and function is a crucial first step toward understand-ing underlying molecular mechanisms. This information will, in turn, lead us to new therapeutics and to a better understanding of environmental influences on the devel-oping nervous system.

The SSC aims to establish a repository of genetic samples and phenotypic data from simplex families, where one child is diagnosed with an Autism Spectrum Disorder while both parents and other siblings are unaffected. Our initial goal is to identify de novo copy number variants (chromosomal deletions or duplications) in probands from 2,000 families.

To deal with the massive amounts of phenotypic and genetic data, we have created an interactive database called SFARI Base that will allow sophisticated queries of the data, and hopefully uncover new correlations.

We recently unveiled SFARI Gene, a new online autism gene database that appears on our website at http://gene.sfari.org. SFARI Gene collects information on genes linked to Autism Spectrum Disorders from the published scientific literature. This publicly available database will be expanded by addition of new, interactive modules that incorporate genetic structural alterations as well as biochemical, physiological and anatomic data.

From the SFARI Director“To deal with the massive amounts of phenotypic and genetic data, we have created an interactive database called SFARI Base that will allow sophisticated queries of the data, and hopefully uncover new correlations.”


A critically important “tool” is an interactive community of scholars dedicated to shar-ing information, research reagents, animals, and most important, ideas to enhance autism research. To build this community, we have organized a series of workshops at the Simons Foundation and many discussions with individuals and small groups, and we are looking forward to our first Annual Science Meeting in New Orleans in April 2009. We will expand the number of workshops in the coming year as collabo-rations expand and questions become better defined. Our website will serve as an important resource for Simons Investigators and for all other scientists with interests in related areas.

At the present time, we fund research in three areas: gene discovery, molecular mechanisms, and cognition and behavior. Our hope is to blur the distinctions, tech-nical hurdles and strategic barriers that keep these approaches too far apart. A list of Simons Investigators can be found at http://sfari.org/simons-investigators.

We are not alone in the effort to understand autism. This effort goes to the core of the human condition, so one can expect that real advances will take the combined efforts of a worldwide community of scientists of all stripes. We look forward to building partnerships in the coming years.

Gerald D. FischbachSFARI Director

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From the very beginning of his medical training, John Constantino has coupled rigorous clinical research with teaching social workers, educators and parents about children’s mental health.

In 1999, he helped develop the first scale of traits of people on the autism spectrum that is quick and easy enough for general practitioners and school teachers to use.

Since its commercial release in 2005, the test, the Social Responsiveness Scale (SRS), has been published in seven languages and is set to be available in eight more. Clinicians say it’s one of the most reliable measures of autism, and has a 70% correlation with scores on the ADI-R – the gold standard of autism diagnoses.

The SRS’s 65-item questionnaire focuses on reciprocal social behavior, such as the ability to understand and respond to emotional cues from others, and takes just 15 to 20 minutes to complete.

On the basis of the first sets of SRS data, Constantino found that the three domains of autism – social impair-ment, language impairment and repetitive behav-

iors – are not independent of each other. “It seems that they’re very tightly connected to each other and that some underlying cause may produce symptoms in all three domains of autism at the same time,” he says.

The SRS has also allowed Constantino to quantitatively study the ‘broader autism phenotype’ – milder behav-ioral, neurobiological or anatomical traits in the siblings and parents of children with autism – and to increase the statistical power of traditional linkage studies.

“How is it that some individuals have subtle autistic social impairments that fall below the level of severity seen in fully affected children?” he asks. “Understanding this can provide insight into the confluence of factors that give rise to the full autistic syndrome.”

John Constantino

“ How is it that you can have part of the syndrome, but not all of it?”

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People on the autism spectrum tend to exhibit repeti-tive behaviors – a characteristic that’s also seen in those with obsessive-compulsive disorder (OCD).

Neurobiologist Guoping Feng is searching for the genetic basis of repetitive behaviors by unraveling the mechanisms at work in OCD.

In August 2007, Feng and his colleagues at the Duke University Medical Center published the first well-described mouse model of OCD, a disorder defined by recurrent, unwanted thoughts and aimless rituals. The researchers focused on SAPAP3, a protein that provides scaffolding at the synapse, the junction at which nerve cells communicate. By deleting the gene for SAPAP3, the researchers were able to turn healthy mice into compulsive, round-the-clock groomers that scratched the hair right off their faces.

Using up to 400 samples from the Simons Simplex Collection, a gene bank of children on the autism spec-trum and their families, Feng’s team plans to look for mutations in SAPAP3 and about 20 other genes that encode synaptic proteins.

Feng’s team reported in a January 2009 paper that they had found rare mutations in the SAPAP3 gene in 4.2 percent of people with OCD, compared with 1.1 percent in a control group without OCD.

“Many steps can affect circuitry function, but the syn-apse is definitely one of the key places where some-thing can go wrong,” Feng says.

The synapse is likely to prove equally important in autism, Feng says. SAPAP3 interacts directly with another synaptic protein, SHANK3, mutations in which have been associated with autism.

SAPAP3 and SHANK3 are expressed highly in syn-apses located in the striatum – the deep, central brain region that is known to undergo changes in people with OCD. Some studies have also found abnormally large striatal volumes in people on the autism spectrum.

“We think that compulsive behavior in OCD and autism may have a common circuitry mechanism,” Feng says.

“Our goal now is to look at how the genes [causing] synaptic defects in the striatum are related to autism.”

Guoping Feng

“Our goal now is to look at how the genes [causing] synaptic defects in the striatum are related to autism.”


In August 2001, neurogeneticist Daniel Geschwind and other researchers affiliated with the nonprofit Cure Autism Now created the Autism Genetic Resource Exchange (AGRE), a gene bank of more than 4,500 samples from families in which at least two children have autism.

Since then, using the AGRE samples, Geschwind has led many of the largest high-resolution genome scans intended to pinpoint the chromosomal anomalies in people on the autism spectrum.

At the University of California, Los Angeles, Geschwind’s lab studies brain asymmetry, fronto-temporal dementia and other neurological diseases. But its main focus is the genetics of autism. In particular, Geschwind is seeking genetic similarities among people with autism who share endophenotypes – quantifiable markers of disease – such as sex, language ability and social impairment.

For instance, his team found in January 2008 that a gene thought to be involved in nerve cell communica-tion, contactin-associated protein-like 2 or CNTNAP2, is associated with autism and language deficits in

males. In November 2008, the researchers linked CNTNAP2 to families with specific language impair-ment, another childhood development disorder.

Geschwind, whose first career was strategic business consulting, says “you’d need a crystal ball” to know where the rapidly growing autism field is headed, par-ticularly because it comprises such a diverse spectrum of behavioral and genetic characteristics.

“What we’ve learned most is that autism is far more heterogeneous than any of us expected,” he says.

“But on the other hand, nowhere has there been more progress in genetics in any complex neuropsychiatric disease than in autism.”

Dan Geschwind

“ Nowhere has there been more progress in genetics in any complex disease than in autism.”

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‘Theory of mind’ – the ability to sense what other people want, believe or intend – has fascinated philosophers and psychologists for centuries. But it wasn’t until 2003 that Rebecca Saxe, then a graduate student, identified a precise region in the brain, a part of the temporo-parietal junction, that's active when we try to divine others’ thoughts.

Now an assistant professor at the Massachusetts Institute of Technology’s Department of Brain and Cognitive Sciences, Saxe is using functional magnetic resonance imaging to study social cognition in people on the autism spectrum, who often have trouble grasp-ing what others are thinking.

In one experiment, for instance, Saxe uses a new pro-cedure in which live video displays brain activity during real-time, back-and-forth social interaction – a measure that she predicts will be strikingly different in people with autism.

Saxe plans other autism-related experiments, including brain scans of people on the spectrum making moral judgments, and a comprehensive survey of how spe-cific brain regions develop in babies at risk of develop-ing autism and in healthy controls.

“My gut instinct about the mind – and I don’t know about autism, but I’m trying what I know – is that the answers are not going to be at the level of the biology,” she says. “The answers are going to be at the level of the systems.”

Rebecca Saxe

“ The answers are not going to be at the level of the biology, the answers are going to be at the level of the systems.”

Left: Close-up of a syringe injecting buffer fluid into a sequencer gel. The gel will then be loaded into a sequencer, which will automatically analyze the DNA molecules.

Right: Dr. Michael Wigler, a researcher at Cold Spring Harbor Laboratory.


The Simons Simplex Collection (SSC) aims to collect DNA and phenotypic information from 2,000 ‘simplex’ families, in which one child has autism but siblings and parents are unaffected. The SSC is a collabora-tion of 13 university-affiliated research clinics across the United States and Canada, under the guidance of the University of Michigan Autism & Communication Disorders Center. The clinics follow meticulous phe-notype protocols, and this information is paired with genetic data from the blood samples.

Using different technologies, groups led by Michael Wigler, of Cold Spring Harbor Laboratory, and Matthew State, of Yale University, are analyzing the samples to detect copy number variations – chunks of DNA that are duplicated or deleted.

Here, Dr. Wigler discusses the evolution of the SSC.

How did the idea for the SSC come about? We had preliminary results that de novo (spontaneous or new) copy number variations are present at a higher

rate in kids with autism than in unaffected children, but we only saw this as a significant difference in the so-called ‘simplex’ families, families with only one child on the spectrum. This effect was not significant in families with multiple children on the spectrum (the ‘multiplex’ families). We were discovering new mutations – things that occur spontaneously in the parental germ line. So you wouldn’t expect two kids in the multiplex family to have them. Previous autism collections were devoted to multiplex families. We decided that it would be very use-ful to have a collection devoted to the simplex families.

What's the status of the collection?

We’ve been getting samples since March 2008, and we’ve only [genotyped] the first 250 families. But the results that we saw previously are holding up. There’s also a strong genomic asymmetry in boys and girls.

Why use two methods to genotype the data?

Why do you have two lungs? In case one of them fails. There’s a little bit more information of one type that

Michael Wigler Q&A“We were discovering new mutations – things that occur spontaneously in the parental germ line.”

Left: Electrophoresis gel.

Right: Fluorescence microscopy of chromosomes.

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“The real goal is to find the genes that are causing autism, so that we can formulate a neurophysiologic hypothesis for why a child is on the spectrum.”

you can get from the Yale method, and a little bit more resolution that you can get from our method. The two platforms search for copy number variations using dif-ferent strategies.

What are your genotyping goals for the end of 2009?

We’d like to identify several hundred loci [the area on a chromosome where a particular gene is located]. Hopefully some of these will be recurrent. That is, they will be independently occurring events that tell us this region is important. The real goal is to find the genes that are causing autism, so that we can formulate a neurophysiologic hypothesis for why a child is on the spectrum. We should be further along in 2009, by at least threefold more families than we have now.

Another goal is to see if there are common polymor-phisms [common genetic variations in the general pop-ulation] that are associated with autism. So far, there’s no evidence that these things exist. They would be very important to find. For instance, why are girls less likely to be on the spectrum? It’s got to be something genetic ultimately. It would be an enormously useful clue if we could see something like that.


How the SSC WorksThe primary goal of the Simons Simplex Collection is to establish a permanent repository of genetic samples from 2,000 families, each of which has one child affected with an autism spectrum disorder (ASD) and parents unaffected with ASD. Each genetic sample will have an associated collection of data that provides a precise characterization of the individual (phenotype). Rigorous phenotyping will maximize the value of the resource for a wide variety of future research into the causes and mechanisms of autism.

Visit http://sfari.org/ssc

Families with one child on the spectrum are recruited into the collection at 13 sites across North America. Site staff members screen each family to ensure they meet study criteria.

Participating family members complete an extensive testing protocol, including questionnaires, behavioral assessment, cognitive testing, physical exam and blood sample collection.

Families recruited

Blood from each family member is sent to the Rutgers University Cell and DNA Repository (RUCDR) for pro-cessing. The RUCDR runs screening tests, whole-blood DNA extraction and cell line creation.

Blood samples sent to central repository

Phenotype data and blood samples collected

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Approved researchers can access phenotype data directly from SFARI Base. Shipments of biological sam-ples are coordinated through the RUCDR.

Data from researchers is submitted to SFARI Base, continuing to add to the richness of the information.

Final phenotype data published in SFARI Base data repository

Researchers request access and submit findings

Data are reviewed and validated by a panel. The review includes diagnoses, behavioral assessment and medi-cal history. Data are made anonymous.

Centralized review of key phenotype data

Financials

Simons Foundation Annual Report 2008 { Financials }26

27

Desintegration d'un kaon positif (meson K+) en vol. © CERN Copyright

This image is taken from one of CERN's bubble chambers and shows the decay of a positive kaon in flight. The decay products of this kaon can be seen spiraling in the magnetic field of the chamber. The invention of bubble chambers in 1952 revolutionized the field of particle physics, allowing real tracks left by particles to be seen and photographed by expanding liquid that has been heated to boiling point.

28 Simons Foundation Annual Report 2008 { Financials }

ASSETS

Cash and Cash Equivalents

Investment Portfolio

Property and Equipment, Net

Prepaid Excise Taxes

Other

Total

LIABILITIES

Grants Payable

Taxes Payable

Deferred Excise Tax Liability

Other

Total

NET ASSETS

UNRESTRICTED NET ASSETS

June 30, 2008

$27,861,666

1,064,269,117

16,094,323

182,146

93,749

1,108,501,001

129,546,444

0

8,659,983

0

138,206,427

$970,294,574

June 30, 2007

$815,022

693,764,890

514,561

0

886,350

695,980,823

76,690,635

2,245,374

7,071,983

265,548

86,273,540

$609,707,283

Balance Sheet

29

REVENUE

Contributions

Investment Income

Total

EXPENSES

Grants Paid

Change in Grants Payable

General and Administrative

Program

Depreciation and Amortization

Federal Excise Taxes

Other

Total

NET INCOME

June 30, 2008

$180,480,577

290,467,232

470,947,809

47,660,532

52,855,809

1,649,880

5,287,127

222,199

2,908,800

0

110,584,347

$360,363,462

Income Statement

June 30, 2007

$70,923,570

182,565,644

253,489,214

32,607,522

47,349,034

817,816

1,102,637

164,939

3,633,092

89,000

85,764,040

$167,725,174

Proportions of Expenses ($’s in Thousands)

30

Marilyn H. Simons, Ph.D. President

Marilyn Hawrys Simons has worked primarily in the nonprofit sector as a volunteer for the past 20 years, focusing on education. She has served as president of the Simons Foundation since 1994. Ms. Simons is currently president of the board of LearningSpring School, a school for children diagnosed with autism spectrum disor-ders, and is a member of the board of trustees of the East Harlem Tutorial Program. Ms. Simons is also a trustee of the Cold Spring Harbor Laboratory. She received a B.A. and a Ph.D. in economics from the State University of New York at Stony Brook.

James H. Simons, Ph.D. Secretary and Treasurer

James H. Simons, Ph.D., is secretary and treasurer of the Simons Foundation. Dr. Simons is president and founder of Renaissance Technologies. Prior to his finan-cial career, Dr. Simons served as chairman of the Mathematics Department at the State University of New York at Stony Brook, taught mathematics at Massachusetts Institute of Technology and Harvard University, and was a cryptanalyst at the Institute of Defense Analyses in Princeton, N.J. Dr. Simons’ scientific work was in the area of geometry and topology, and his most influential work involved the discovery and application of certain measurements, now called Chern-Simons invariants, which have had wide use, particularly in theoretical physics. Dr. Simons holds a B.S. from the Massachusetts Institute of Technology and a Ph.D. from the University of California, Berkeley, and won the American Mathematical Society’s Veblen Prize for his work in geometry in 1975. He is a former chairman of the Stony Brook Foundation and is currently a trustee of Rockefeller University, Massachusetts Institute of Technology, Brookhaven National Laboratory, the Mathematical Sciences Research Institute and the Institute for Advanced Study.

Mark Silber, J.D., M.B.A. Vice President

Mark Silber, J.D., M.B.A., is vice president and general counsel at Renaissance Technologies, where he has held responsibility for finance, administration and compliance since joining the firm in 1983. Prior to joining Renaissance, he was a Certified Public Accountant with the accounting firm of Seidman & Seidman, now BDO Seidman. Mr. Silber holds a bachelor’s degree from Brooklyn College, a J.D. and L.L.M. in tax law from the New York University School of Law, and an M.B.A. in finance from the New York University Graduate School of Business Administration.

Trustees

Simons Foundation Annual Report 2008 { Simons Staff }

31

Marilyn Simons, Ph.D. President

James H. Simons, Ph.D. Secretary and Treasurer

Maria Adler, M.B.A. Vice President, Finance

Marta Benedetti, Ph.D. Associate Director for Research

Sascha Brodsky, M.S., M.I.A. Director of Communications

Meghan Criswell Administrative Assistant

Gerald D. Fischbach, M.D. Scientific Director

Chris Fleisch, B.S. Programmer/Analyst

Andrea Gallego, B.A. Executive Assistant

Adrienne Greenberg, B.S. Business Manager

Marion Greenup, M.P.H., M.Ed. Vice President, Administration

Stephen Johnson, Ph.D. Informatics Director

Apoorva Mandavilli, M.S., M.A. Executive Editor

Alan Packer, Ph.D. Associate Director for Research (not pictured)

Amy Pasquariello, B.A. Project Manager, SFARI

Lauren Rath, B.A. Grants Associate

John Spiro, Ph.D. Senior Associate Director for Research

Patricia Weisenfeld, M.P.A. Director of Family Giving

Simons Foundation Staff

Connect and Collaborate

Simons Foundation Annual Report 2008 { Simons Grants }32

The Simons Foundation supports outstanding individual researchers and institutions seeking funding for advanced work in the basic sciences and mathematics, with a focus on innovative scientific projects where our involvement will play an essential role. In the course of this support, the foundation is interested in partnering with other entities, or providing matching support where appropriate.

Historically, the Simons Foundation has accepted only solicited grant proposals. All grant decisions are made by the trustees of the foundation and the foundation staff. The foundation does not make awards to individuals, except through their institutions.

Simons Investigators

Ralph Adolphs California Institute of Technology

John M. Allman California Institute of Technology

Mark Bear Massachusetts Institute of Technology

Arthur Beaudet Baylor College of Medicine

Raphael Bernier University of Washington

Joseph Buxbaum Mount Sinai School of Medicine

Brian Chait The Rockefeller University

Aravinda Chakravarti Johns Hopkins University School of Medicine

Andrew Chess Massachusetts General Hospital

John Constantino Washington University

Edwin Cook, Jr. University of Illinois at Chicago

Eric Courchesne University of California, San Diego

Mark Daly Massachusetts General Hospital

Ted M. Dawson Johns Hopkins University School of Medicine

Curtis Deutsch University of Massachusetts Medical School

Michael D. Ehlers Duke University

Guoping Feng Duke University

Gordon J. Fishell New York University School of Medicine

Eric Fombonne McGill University

John Gabrieli Massachusetts Institute of Technology

Daniel Geschwind University of California, Los Angeles

Jay Gingrich Research Foundation for Mental Hygiene, Inc., New York State Psychiatric Institute

Joseph Gogos Columbia University

Ann Graybiel Massachusetts Institute of Technology

Paul Greengard The Rockefeller University

James F. Gusella Massachusetts General Hospital

Nathaniel Heintz The Rockefeller University

Barbara Hempstead Weill Medical College of Cornell University

Z. Josh Huang Cold Spring Harbor Laboratory

34 Simons Foundation Annual Report 2008 { Simons Grants }

Eric R. Kandel Columbia University

Ami Klin Yale University

Richard Krauzlis Salk Institute for Biological Studies

Abba Krieger University of Pennsylvania

Louis Kunkel Children's Hospital Boston

David Ledbetter Emory University

Arnold J. Levine Institute for Advanced Study

Pat Levitt Vanderbilt University

Dan Littman New York University School of Medicine

Catherine Lord University of Michigan

Christa Lese Martin Emory University

Steven McKnight University of Texas Southwestern Medical Center

Judith Miles University of Missouri

Alea Mills Cold Spring Harbor Laboratory

Anthony Monaco University of Oxford

Daniel Notterman Princeton University

Opal Ousley Emory University

Luis Parada University of Texas Southwestern Medical Center

Karen Parker Stanford University

Paul Patterson California Institute of Technology

Kevin Pelphrey Yale University

Bradley Peterson Columbia University

Judith Piggot University of California, Los Angeles

Joseph Piven University of North Carolina at Chapel Hill

Vijaya Ramesh Massachusetts General Hospital

Louis Reichardt University of California, San Francisco

Bernardo Sabatini Harvard Medical School

Joshua Sanes Harvard University

Rebecca Saxe Massachusetts Institute of Technology

Morgan Sheng Massachusetts Institute of Technology

Maggie Shiffrar Rutgers, The State University of New Jersey

Pawan Sinha Massachusetts Institute of Technology

Hazel Sive Whitehead Institute for Biomedical Research

Matthew State Yale University

Thomas Südhof Stanford University

David Sulzer Columbia University

Mriganka Sur Massachusetts Institute of Technology

James Sutcliffe Vanderbilt University

Susumu Tonegawa Massachusetts Institute of Technology

Li-Huei Tsai Massachusetts Institute of Technology

Richard Tsien Stanford University

Michael Ullman Georgetown University

Christopher Walsh Beth Israel Deaconess Medical Center

Stephen Warren Emory University

Zachary Warren Vanderbilt University

Michael Wigler Cold Spring Harbor Laboratory

Huda Zoghbi Baylor College of Medicine

35

36 Simons Foundation Annual Report 2008 { Simons Grants }

Grants to Institutions

Math and Physical Science

American University of Beirut Beirut, Lebanon

Friends of the Institut des Hautes Études Scientifiques New York, New York

Harvard University Cambridge, Massachusetts

Massachusetts Institute of Technology Cambridge, Massachusetts

Mathematical Sciences Research Institute Berkeley, California

Science Festival Foundation New York, New York

S. S. Chern Foundation for Mathematical Research Beijing, China

Stony Brook University Stony Brook, New York

Tsinghua Education Foundation Beijing, China

University of California, Berkeley Berkeley, California

Math and Science Education

Aquarium of the Pacific Long Beach, California

Fannie & John Hertz Foundation Livermore, California

Math for America New York, New York

New England Aquarium Boston, Massachusetts

Ohio State University Columbus, Ohio

Life Sciences

Beth Israel Deaconess Medical Center Boston, Massachusetts

Cold Spring Harbor Laboratory Cold Spring Harbor, New York

Institute for Advanced Study Princeton, New Jersey

Memorial Sloan-Kettering Cancer Center New York, New York

The Rockefeller University New York, New York

Autism

Baylor College of Medicine Houston, Texas

Beth Israel Deaconess Medical Center Boston, Massachusetts

California Institute of Technology Pasadena, California

Children’s Hospital Boston Boston, Massachusetts

Children’s Hospital Philadelphia Philadelphia, Pennsylvania

Cold Spring Harbor Laboratory Cold Spring Harbor, New York

Columbia University New York, New York

Cornell University New York, New York

Duke University Durham, North Carolina

Emory University Atlanta, Georgia

Georgetown University Washington, District of Columbia

Harvard Medical School Boston, Massachusetts

Johns Hopkins University Baltimore, Maryland

Massachusetts General Hospital Boston, Massachusetts

Massachusetts Institute of Technology Cambridge, Massachusetts

McGill University Montreal, Canada

Mount Sinai School of Medicine New York, New York

New York University School of Medicine New York, New York

37

Princeton University Princeton, New Jersey

Research Foundation for Mental Hygiene, Inc., at New York State Psychiatric Institute New York, New York

Rockefeller University New York, New York

Rutgers, The State University of New Jersey New Brunswick, New Jersey

Salk Institute for Biological Studies La Jolla, California

Stanford University Menlo Park, California

University of California, Los Angeles Los Angeles, California

University of California, San Diego San Diego, California

University of California, San Francisco San Francisco, California

University of Illinois at Chicago Chicago, Illinois

University of Massachusetts Medical School Worcester, Massachusetts

University of Michigan Ann Arbor, Michigan

University of Missouri Columbia, Missouri

University of North Carolina at Chapel Hill Chapel Hill, North Carolina

University of Oxford Oxford, England

University of Pennsylvania Philadelphia, Pennsylvania

University of Texas Southwestern Medical Center Dallas, Texas

University of Washington Seattle, Washington

Vanderbilt University Nashville, Tennessee

Washington University in St. Louis St. Louis, Missouri

Whitehead Institute for Biomedical Research Cambridge, Massachusetts

Yale University New Haven, Connecticut

Dennis W. Choi, M.D., Ph.D. Emory University

Wendy Chung, M.D., Ph.D. Columbia University Medical Center

Thomas M. Jessell, Ph.D. Columbia University

Nancy Kanwisher, Ph.D. Massachusetts Institute of Technology

Richard P. Lifton, M.D., Ph.D. Yale University

Catherine E. Lord, Ph.D. University of Michigan Autism and Communication Disorders Center

J. Anthony Movshon, Ph.D. New York University School of Medicine

Martin Raff, M.D. University College London

SFARI Scientific Advisory Board

38 Simons Foundation Annual Report 2008 { Contact }

For more information on the Simons Foundation and SFARI, please visit our websites:

simonsfoundation.orgsfari.org

The Flower of Maths was quoted on page 5 with permission from “The Unravelers: Mathematical Snapshots,” AK Peters Ltd, 2008.

All photos on the bottom of pages 10 and 11 are courtesy of IHÉS and appear in the book,

“The Unravelers: Mathematical Snapshots,” © Copyright Jean-François Dars, AK Peters Ltd, 2008.

Michael Atiyah was quoted on page 12 with permission from “The Unravelers: Mathematical Snapshots,” AK Peters Ltd, 2008.

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The Simons Foundation 2008 Annual Report

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Transcript of The Simons Foundation 2008 Annual Report