From Stanford University (US) : “Stanford researchers develop tool to drastically speed up the study of enzymes”

Stanford University Name

From Stanford University (US)

July 22, 2021
Ker Than

A new tool that enables thousands of tiny experiments to run simultaneously on a single polymer chip will let scientists study enzymes faster and more comprehensively than ever before.

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HT-MEK – short for High-Throughput Microfluidic Enzyme Kinetics – combines microfluidics and cell-free protein synthesis technologies to dramatically speed up the study of enzymes. Credit: Daniel Mokhtari.

For much of human history, animals and plants were perceived to follow a different set of rules than rest of the universe. In the 18th and 19th centuries, this culminated in a belief that living organisms were infused by a non-physical energy or “life force” that allowed them to perform remarkable transformations that couldn’t be explained by conventional chemistry or physics alone.

Scientists now understand that these transformations are powered by enzymes – protein molecules comprised of chains of amino acids that act to speed up, or catalyze, the conversion of one kind of molecule (substrates) into another (products). In so doing, they enable reactions such as digestion and fermentation – and all of the chemical events that happen in every one of our cells – that, left alone, would happen extraordinarily slowly.

“A chemical reaction that would take longer than the lifetime of the universe to happen on its own can occur in seconds with the aid of enzymes,” said Polly Fordyce, an assistant professor of bioengineering and of genetics at Stanford University.

While much is now known about enzymes, including their structures and the chemical groups they use to facilitate reactions, the details surrounding how their forms connect to their functions, and how they pull off their biochemical wizardry with such extraordinary speed and specificity are still not well understood.

A new technique, developed by Fordyce and her colleagues at Stanford and detailed this week in the journal Science, could help change that. Dubbed HT-MEK — short for High-Throughput Microfluidic Enzyme Kinetics — the technique can compress years of work into just a few weeks by enabling thousands of enzyme experiments to be performed simultaneously. “Limits in our ability to do enough experiments have prevented us from truly dissecting and understanding enzymes,” said study co-leader Dan Herschlag, a professor of biochemistry at Stanford’s School of Medicine.

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Closeup image of the HT-MEK device shows the individual nanoliter-sized chambers where enzyme experiments are performed. Credit: Daniel Mokhtari.

By allowing scientists to deeply probe beyond the small “active site” of an enzyme where substrate binding occurs, HT-MEK could reveal clues about how even the most distant parts of enzymes work together to achieve their remarkable reactivity.

“It’s like we’re now taking a flashlight and instead of just shining it on the active site we’re shining it over the entire enzyme,” Fordyce said. “When we did this, we saw a lot of things we didn’t expect.”

Enzymatic tricks

HT-MEK is designed to replace a laborious process for purifying enzymes that has traditionally involved engineering bacteria to produce a particular enzyme, growing them in large beakers, bursting open the microbes and then isolating the enzyme of interest from all the other unwanted cellular components. To piece together how an enzyme works, scientists introduce intentional mistakes into its DNA blueprint and then analyze how these mutations affect catalysis.

This process is expensive and time consuming, however, so like an audience raptly focused on the hands of a magician during a conjuring trick, researchers have mostly limited their scientific investigations to the active sites of enzymes. “We know a lot about the part of the enzyme where the chemistry occurs because people have made mutations there to see what happens. But that’s taken decades,” Fordyce said.

But as any connoisseur of magic tricks knows, the key to a successful illusion can lie not just in the actions of the magician’s fingers, but might also involve the deft positioning of an arm or the torso, a misdirecting patter or discrete actions happening offstage, invisible to the audience. HT-MEK allows scientists to easily shift their gaze to parts of the enzyme beyond the active site and to explore how, for example, changing the shape of an enzyme’s surface might affect the workings of its interior.

“We ultimately would like to do enzymatic tricks ourselves,” Fordyce said. “But the first step is figuring out how it’s done before we can teach ourselves to do it.”

Enzyme experiments on a chip

The technology behind HT-MEK was developed and refined over six years through a partnership between the labs of Fordyce and Herschlag. “This is an amazing case of engineering and enzymology coming together to — we hope — revolutionize a field,” Herschlag said. “This project went beyond your typical collaboration — it was a group of people working jointly to solve a very difficult problem — and continues with the methodologies in place to try to answer difficult questions.”

HT-MEK combines two existing technologies to rapidly speed up enzyme analysis. The first is microfluidics, which involves molding polymer chips to create microscopic channels for the precise manipulation of fluids. “Microfluidics shrinks the physical space to do these fluidic experiments in the same way that integrated circuits reduced the real estate needed for computing,” Fordyce said. “In enzymology, we are still doing things in these giant liter-sized flasks. Everything is a huge volume and we can’t do many things at once.”

The second is cell-free protein synthesis, a technology that takes only those crucial pieces of biological machinery required for protein production and combines them into a soupy extract that can be used to create enzymes synthetically, without requiring living cells to serve as incubators.

“We’ve automated it so that we can use printers to deposit microscopic spots of synthetic DNA coding for the enzyme that we want onto a slide and then align nanoliter-sized chambers filled with the protein starter mix over the spots,” Fordyce explained.

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The scientists used HT-MEK to study how mutations to different parts of a well-studied enzyme called PafA affected its catalytic ability. Credit: Daniel Mokhtari.

Because each tiny chamber contains only a thousandth of a millionth of a liter of material the scientists can engineer thousands of variants of an enzyme in a single device and study them in parallel. By tweaking the DNA instructions in each chamber, they can modify the chains of amino acid molecules that comprise the enzyme. In this way, it’s possible to systematically study how different modifications to an enzyme affects its folding, catalytic ability and ability to bind small molecules and other proteins.

When the team applied their technique to a well-studied enzyme called PafA, they found that mutations well beyond the active site affected its ability to catalyze chemical reactions — indeed, most of the amino acids, or “residues,” making up the enzyme had effects.

The scientists also discovered that a surprising number of mutations caused PafA to misfold into an alternate state that was unable to perform catalysis. “Biochemists have known for decades that misfolding can occur but it’s been extremely difficult to identify these cases and even more difficult to quantitatively estimate the amount of this misfolded stuff,” said study co-first author Craig Markin, a research scientist with joint appointments in the Fordyce and Herschlag labs.

“This is one enzyme out of thousands and thousands,” Herschlag emphasized. “We expect there to be more discoveries and more surprises.”

Accelerating advances

If widely adopted HT-MEK could not only improve our basic understanding of enzyme function but also catalyze advances in medicine and industry, the researchers say. “A lot of the industrial chemicals we use now are bad for the environment and are not sustainable. But enzymes work most effectively in the most environmentally benign substance we have — water,” said study co-first author Daniel Mokhtari, a Stanford graduate student in the Herschlag and Fordyce labs.


Movie shows fluorescence buildup denoting catalytic reactions in a portion of the HT-MEK device over time. Credit: Craig Markin and Daniel Mokhtari.

HT-MEK could also accelerate an approach to drug development called allosteric targeting which aims to increase drug specificity by targeting beyond an enzyme’s active site. Enzymes are popular pharmaceutical targets because of the key role they play in biological processes. But some are considered “undruggable” because they belong to families of related enzymes that share the same or very similar active sites, and targeting them can lead to side effects. The idea behind allosteric targeting is to create drugs that can bind to parts of enzymes that tend to be more differentiated, like their surfaces, but still control particular aspects of catalysis. “With PafA, we saw functional connectivity between the surface and the active site, so that gives us hope that other enzymes will have similar targets,” Markin said. “If we can identify where allosteric targets are, then we’ll be able to start on the harder job of actually designing drugs for them.”

The sheer amount of data that HT-MEK is expected to generate will also be a boon to computational approaches and machine learning algorithms, like the Google-funded AlphaFold project designed to deduce an enzyme’s complicated 3D shape from its amino acid sequence alone. “If machine learning is to have any chance of accurately predicting enzyme function, it will need the kind of data HT-MEK can provide to train on,” Mokhtari said.

Much further down the road, HT-MEK may even allow scientists to reverse-engineer enzymes and design bespoke varieties of their own. “Plastics are a great example,” Fordyce said. “We would love to create enzymes that can degrade plastics into nontoxic and harmless pieces. If it were really true that the only part of an enzyme that matters is its active site, then we’d be able to do that and more already. Many people have tried and failed, and it’s thought that one reason why we can’t is because the rest of the enzyme is important for getting the active site in just the right shape and to wiggle in just the right way.”

Herschlag hopes that adoption of HT-MEK among scientists will be swift. “If you’re an enzymologist trying to learn about a new enzyme and you have the opportunity to look at 5 or 10 mutations over six months or 100 or 1,000 mutants of your enzyme over the same period, which would you choose?” he said. “This is a tool that has the potential to supplant traditional methods for an entire community.”

See the full article here .


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Stanford University (US)

Leland and Jane Stanford founded the University to “promote the public welfare by exercising an influence on behalf of humanity and civilization.” Stanford opened its doors in 1891, and more than a century later, it remains dedicated to finding solutions to the great challenges of the day and to preparing our students for leadership in today’s complex world. Stanford, is an American private research university located in Stanford, California on an 8,180-acre (3,310 ha) campus near Palo Alto. Since 1952, more than 54 Stanford faculty, staff, and alumni have won the Nobel Prize, including 19 current faculty members.

Stanford University, officially Leland Stanford Junior University, is a private research university located in Stanford, California. Stanford was founded in 1885 by Leland and Jane Stanford in memory of their only child, Leland Stanford Jr., who had died of typhoid fever at age 15 the previous year. Stanford is consistently ranked as among the most prestigious and top universities in the world by major education publications. It is also one of the top fundraising institutions in the country, becoming the first school to raise more than a billion dollars in a year.

Leland Stanford was a U.S. senator and former governor of California who made his fortune as a railroad tycoon. The school admitted its first students on October 1, 1891, as a coeducational and non-denominational institution. Stanford University struggled financially after the death of Leland Stanford in 1893 and again after much of the campus was damaged by the 1906 San Francisco earthquake. Following World War II, provost Frederick Terman supported faculty and graduates’ entrepreneurialism to build self-sufficient local industry in what would later be known as Silicon Valley.

The university is organized around seven schools: three schools consisting of 40 academic departments at the undergraduate level as well as four professional schools that focus on graduate programs in law, medicine, education, and business. All schools are on the same campus. Students compete in 36 varsity sports, and the university is one of two private institutions in the Division I FBS Pac-12 Conference. It has gained 126 NCAA team championships, and Stanford has won the NACDA Directors’ Cup for 24 consecutive years, beginning in 1994–1995. In addition, Stanford students and alumni have won 270 Olympic medals including 139 gold medals.

As of October 2020, 84 Nobel laureates, 28 Turing Award laureates, and eight Fields Medalists have been affiliated with Stanford as students, alumni, faculty, or staff. In addition, Stanford is particularly noted for its entrepreneurship and is one of the most successful universities in attracting funding for start-ups. Stanford alumni have founded numerous companies, which combined produce more than $2.7 trillion in annual revenue, roughly equivalent to the 7th largest economy in the world (as of 2020). Stanford is the alma mater of one president of the United States (Herbert Hoover), 74 living billionaires, and 17 astronauts. It is also one of the leading producers of Fulbright Scholars, Marshall Scholars, Rhodes Scholars, and members of the United States Congress.

Stanford University was founded in 1885 by Leland and Jane Stanford, dedicated to Leland Stanford Jr, their only child. The institution opened in 1891 on Stanford’s previous Palo Alto farm.

Jane and Leland Stanford modeled their university after the great eastern universities, most specifically Cornell University. Stanford opened being called the “Cornell of the West” in 1891 due to faculty being former Cornell affiliates (either professors, alumni, or both) including its first president, David Starr Jordan, and second president, John Casper Branner. Both Cornell and Stanford were among the first to have higher education be accessible, nonsectarian, and open to women as well as to men. Cornell is credited as one of the first American universities to adopt this radical departure from traditional education, and Stanford became an early adopter as well.

Despite being impacted by earthquakes in both 1906 and 1989, the campus was rebuilt each time. In 1919, The Hoover Institution on War, Revolution and Peace was started by Herbert Hoover to preserve artifacts related to World War I. The Stanford Medical Center, completed in 1959, is a teaching hospital with over 800 beds. The DOE’s SLAC National Accelerator Laboratory(US)(originally named the Stanford Linear Accelerator Center), established in 1962, performs research in particle physics.

Land

Most of Stanford is on an 8,180-acre (12.8 sq mi; 33.1 km^2) campus, one of the largest in the United States. It is located on the San Francisco Peninsula, in the northwest part of the Santa Clara Valley (Silicon Valley) approximately 37 miles (60 km) southeast of San Francisco and approximately 20 miles (30 km) northwest of San Jose. In 2008, 60% of this land remained undeveloped.

Stanford’s main campus includes a census-designated place within unincorporated Santa Clara County, although some of the university land (such as the Stanford Shopping Center and the Stanford Research Park) is within the city limits of Palo Alto. The campus also includes much land in unincorporated San Mateo County (including the SLAC National Accelerator Laboratory and the Jasper Ridge Biological Preserve), as well as in the city limits of Menlo Park (Stanford Hills neighborhood), Woodside, and Portola Valley.

Non-central campus

Stanford currently operates in various locations outside of its central campus.

On the founding grant:

Jasper Ridge Biological Preserve is a 1,200-acre (490 ha) natural reserve south of the central campus owned by the university and used by wildlife biologists for research.
SLAC National Accelerator Laboratory is a facility west of the central campus operated by the university for the Department of Energy. It contains the longest linear particle accelerator in the world, 2 miles (3.2 km) on 426 acres (172 ha) of land.
Golf course and a seasonal lake: The university also has its own golf course and a seasonal lake (Lake Lagunita, actually an irrigation reservoir), both home to the vulnerable California tiger salamander. As of 2012 Lake Lagunita was often dry and the university had no plans to artificially fill it.

Off the founding grant:

Hopkins Marine Station, in Pacific Grove, California, is a marine biology research center owned by the university since 1892.
Study abroad locations: unlike typical study abroad programs, Stanford itself operates in several locations around the world; thus, each location has Stanford faculty-in-residence and staff in addition to students, creating a “mini-Stanford”.

Redwood City campus for many of the university’s administrative offices located in Redwood City, California, a few miles north of the main campus. In 2005, the university purchased a small, 35-acre (14 ha) campus in Midpoint Technology Park intended for staff offices; development was delayed by The Great Recession. In 2015 the university announced a development plan and the Redwood City campus opened in March 2019.

The Bass Center in Washington, DC provides a base, including housing, for the Stanford in Washington program for undergraduates. It includes a small art gallery open to the public.

China: Stanford Center at Peking University, housed in the Lee Jung Sen Building, is a small center for researchers and students in collaboration with Beijing University [北京大学](CN) (Kavli Institute for Astronomy and Astrophysics at Peking University(CN) (KIAA-PKU).

Administration and organization

Stanford is a private, non-profit university that is administered as a corporate trust governed by a privately appointed board of trustees with a maximum membership of 38. Trustees serve five-year terms (not more than two consecutive terms) and meet five times annually.[83] A new trustee is chosen by the current trustees by ballot. The Stanford trustees also oversee the Stanford Research Park, the Stanford Shopping Center, the Cantor Center for Visual Arts, Stanford University Medical Center, and many associated medical facilities (including the Lucile Packard Children’s Hospital).

The board appoints a president to serve as the chief executive officer of the university, to prescribe the duties of professors and course of study, to manage financial and business affairs, and to appoint nine vice presidents. The provost is the chief academic and budget officer, to whom the deans of each of the seven schools report. Persis Drell became the 13th provost in February 2017.

As of 2018, the university was organized into seven academic schools. The schools of Humanities and Sciences (27 departments), Engineering (nine departments), and Earth, Energy & Environmental Sciences (four departments) have both graduate and undergraduate programs while the Schools of Law, Medicine, Education and Business have graduate programs only. The powers and authority of the faculty are vested in the Academic Council, which is made up of tenure and non-tenure line faculty, research faculty, senior fellows in some policy centers and institutes, the president of the university, and some other academic administrators, but most matters are handled by the Faculty Senate, made up of 55 elected representatives of the faculty.

The Associated Students of Stanford University (ASSU) is the student government for Stanford and all registered students are members. Its elected leadership consists of the Undergraduate Senate elected by the undergraduate students, the Graduate Student Council elected by the graduate students, and the President and Vice President elected as a ticket by the entire student body.

Stanford is the beneficiary of a special clause in the California Constitution, which explicitly exempts Stanford property from taxation so long as the property is used for educational purposes.

Endowment and donations

The university’s endowment, managed by the Stanford Management Company, was valued at $27.7 billion as of August 31, 2019. Payouts from the Stanford endowment covered approximately 21.8% of university expenses in the 2019 fiscal year. In the 2018 NACUBO-TIAA survey of colleges and universities in the United States and Canada, only Harvard University(US), the University of Texas System(US), and Yale University(US) had larger endowments than Stanford.

In 2006, President John L. Hennessy launched a five-year campaign called the Stanford Challenge, which reached its $4.3 billion fundraising goal in 2009, two years ahead of time, but continued fundraising for the duration of the campaign. It concluded on December 31, 2011, having raised a total of $6.23 billion and breaking the previous campaign fundraising record of $3.88 billion held by Yale. Specifically, the campaign raised $253.7 million for undergraduate financial aid, as well as $2.33 billion for its initiative in “Seeking Solutions” to global problems, $1.61 billion for “Educating Leaders” by improving K-12 education, and $2.11 billion for “Foundation of Excellence” aimed at providing academic support for Stanford students and faculty. Funds supported 366 new fellowships for graduate students, 139 new endowed chairs for faculty, and 38 new or renovated buildings. The new funding also enabled the construction of a facility for stem cell research; a new campus for the business school; an expansion of the law school; a new Engineering Quad; a new art and art history building; an on-campus concert hall; a new art museum; and a planned expansion of the medical school, among other things. In 2012, the university raised $1.035 billion, becoming the first school to raise more than a billion dollars in a year.

Research centers and institutes

DOE’s SLAC National Accelerator Laboratory(US)
Stanford Research Institute, a center of innovation to support economic development in the region.
Hoover Institution, a conservative American public policy institution and research institution that promotes personal and economic liberty, free enterprise, and limited government.
Hasso Plattner Institute of Design, a multidisciplinary design school in cooperation with the Hasso Plattner Institute of University of Potsdam [Universität Potsdam](DE) that integrates product design, engineering, and business management education).
Martin Luther King Jr. Research and Education Institute, which grew out of and still contains the Martin Luther King Jr. Papers Project.
John S. Knight Fellowship for Professional Journalists
Center for Ocean Solutions
Together with UC Berkeley(US) and UC San Francisco(US), Stanford is part of the Biohub, a new medical science research center founded in 2016 by a $600 million commitment from Facebook CEO and founder Mark Zuckerberg and pediatrician Priscilla Chan.

Discoveries and innovation

Natural sciences

Biological synthesis of deoxyribonucleic acid (DNA) – Arthur Kornberg synthesized DNA material and won the Nobel Prize in Physiology or Medicine 1959 for his work at Stanford.
First Transgenic organism – Stanley Cohen and Herbert Boyer were the first scientists to transplant genes from one living organism to another, a fundamental discovery for genetic engineering. Thousands of products have been developed on the basis of their work, including human growth hormone and hepatitis B vaccine.
Laser – Arthur Leonard Schawlow shared the 1981 Nobel Prize in Physics with Nicolaas Bloembergen and Kai Siegbahn for his work on lasers.
Nuclear magnetic resonance – Felix Bloch developed new methods for nuclear magnetic precision measurements, which are the underlying principles of the MRI.

Computer and applied sciences

ARPANETStanford Research Institute, formerly part of Stanford but on a separate campus, was the site of one of the four original ARPANET nodes.

Internet—Stanford was the site where the original design of the Internet was undertaken. Vint Cerf led a research group to elaborate the design of the Transmission Control Protocol (TCP/IP) that he originally co-created with Robert E. Kahn (Bob Kahn) in 1973 and which formed the basis for the architecture of the Internet.

Frequency modulation synthesis – John Chowning of the Music department invented the FM music synthesis algorithm in 1967, and Stanford later licensed it to Yamaha Corporation.

Google – Google began in January 1996 as a research project by Larry Page and Sergey Brin when they were both PhD students at Stanford. They were working on the Stanford Digital Library Project (SDLP). The SDLP’s goal was “to develop the enabling technologies for a single, integrated and universal digital library” and it was funded through the National Science Foundation, among other federal agencies.

Klystron tube – invented by the brothers Russell and Sigurd Varian at Stanford. Their prototype was completed and demonstrated successfully on August 30, 1937. Upon publication in 1939, news of the klystron immediately influenced the work of U.S. and UK researchers working on radar equipment.

RISCARPA funded VLSI project of microprocessor design. Stanford and UC Berkeley are most associated with the popularization of this concept. The Stanford MIPS would go on to be commercialized as the successful MIPS architecture, while Berkeley RISC gave its name to the entire concept, commercialized as the SPARC. Another success from this era were IBM’s efforts that eventually led to the IBM POWER instruction set architecture, PowerPC, and Power ISA. As these projects matured, a wide variety of similar designs flourished in the late 1980s and especially the early 1990s, representing a major force in the Unix workstation market as well as embedded processors in laser printers, routers and similar products.
SUN workstation – Andy Bechtolsheim designed the SUN workstation for the Stanford University Network communications project as a personal CAD workstation, which led to Sun Microsystems.

Businesses and entrepreneurship

Stanford is one of the most successful universities in creating companies and licensing its inventions to existing companies; it is often held up as a model for technology transfer. Stanford’s Office of Technology Licensing is responsible for commercializing university research, intellectual property, and university-developed projects.

The university is described as having a strong venture culture in which students are encouraged, and often funded, to launch their own companies.

Companies founded by Stanford alumni generate more than $2.7 trillion in annual revenue, equivalent to the 10th-largest economy in the world.

Some companies closely associated with Stanford and their connections include:

Hewlett-Packard, 1939, co-founders William R. Hewlett (B.S, PhD) and David Packard (M.S).
Silicon Graphics, 1981, co-founders James H. Clark (Associate Professor) and several of his grad students.
Sun Microsystems, 1982, co-founders Vinod Khosla (M.B.A), Andy Bechtolsheim (PhD) and Scott McNealy (M.B.A).
Cisco, 1984, founders Leonard Bosack (M.S) and Sandy Lerner (M.S) who were in charge of Stanford Computer Science and Graduate School of Business computer operations groups respectively when the hardware was developed.[163]
Yahoo!, 1994, co-founders Jerry Yang (B.S, M.S) and David Filo (M.S).
Google, 1998, co-founders Larry Page (M.S) and Sergey Brin (M.S).
LinkedIn, 2002, co-founders Reid Hoffman (B.S), Konstantin Guericke (B.S, M.S), Eric Lee (B.S), and Alan Liu (B.S).
Instagram, 2010, co-founders Kevin Systrom (B.S) and Mike Krieger (B.S).
Snapchat, 2011, co-founders Evan Spiegel and Bobby Murphy (B.S).
Coursera, 2012, co-founders Andrew Ng (Associate Professor) and Daphne Koller (Professor, PhD).

Student body

Stanford enrolled 6,996 undergraduate and 10,253 graduate students as of the 2019–2020 school year. Women comprised 50.4% of undergraduates and 41.5% of graduate students. In the same academic year, the freshman retention rate was 99%.

Stanford awarded 1,819 undergraduate degrees, 2,393 master’s degrees, 770 doctoral degrees, and 3270 professional degrees in the 2018–2019 school year. The four-year graduation rate for the class of 2017 cohort was 72.9%, and the six-year rate was 94.4%. The relatively low four-year graduation rate is a function of the university’s coterminal degree (or “coterm”) program, which allows students to earn a master’s degree as a 1-to-2-year extension of their undergraduate program.

As of 2010, fifteen percent of undergraduates were first-generation students.

Athletics

As of 2016 Stanford had 16 male varsity sports and 20 female varsity sports, 19 club sports and about 27 intramural sports. In 1930, following a unanimous vote by the Executive Committee for the Associated Students, the athletic department adopted the mascot “Indian.” The Indian symbol and name were dropped by President Richard Lyman in 1972, after objections from Native American students and a vote by the student senate. The sports teams are now officially referred to as the “Stanford Cardinal,” referring to the deep red color, not the cardinal bird. Stanford is a member of the Pac-12 Conference in most sports, the Mountain Pacific Sports Federation in several other sports, and the America East Conference in field hockey with the participation in the inter-collegiate NCAA’s Division I FBS.

Its traditional sports rival is the University of California, Berkeley, the neighbor to the north in the East Bay. The winner of the annual “Big Game” between the Cal and Cardinal football teams gains custody of the Stanford Axe.

Stanford has had at least one NCAA team champion every year since the 1976–77 school year and has earned 126 NCAA national team titles since its establishment, the most among universities, and Stanford has won 522 individual national championships, the most by any university. Stanford has won the award for the top-ranked Division 1 athletic program—the NACDA Directors’ Cup, formerly known as the Sears Cup—annually for the past twenty-four straight years. Stanford athletes have won medals in every Olympic Games since 1912, winning 270 Olympic medals total, 139 of them gold. In the 2008 Summer Olympics, and 2016 Summer Olympics, Stanford won more Olympic medals than any other university in the United States. Stanford athletes won 16 medals at the 2012 Summer Olympics (12 gold, two silver and two bronze), and 27 medals at the 2016 Summer Olympics.

Traditions

The unofficial motto of Stanford, selected by President Jordan, is Die Luft der Freiheit weht. Translated from the German language, this quotation from Ulrich von Hutten means, “The wind of freedom blows.” The motto was controversial during World War I, when anything in German was suspect; at that time the university disavowed that this motto was official.
Hail, Stanford, Hail! is the Stanford Hymn sometimes sung at ceremonies or adapted by the various University singing groups. It was written in 1892 by mechanical engineering professor Albert W. Smith and his wife, Mary Roberts Smith (in 1896 she earned the first Stanford doctorate in Economics and later became associate professor of Sociology), but was not officially adopted until after a performance on campus in March 1902 by the Mormon Tabernacle Choir.
“Uncommon Man/Uncommon Woman”: Stanford does not award honorary degrees, but in 1953 the degree of “Uncommon Man/Uncommon Woman” was created to recognize individuals who give rare and extraordinary service to the University. Technically, this degree is awarded by the Stanford Associates, a voluntary group that is part of the university’s alumni association. As Stanford’s highest honor, it is not conferred at prescribed intervals, but only when appropriate to recognize extraordinary service. Recipients include Herbert Hoover, Bill Hewlett, Dave Packard, Lucile Packard, and John Gardner.
Big Game events: The events in the week leading up to the Big Game vs. UC Berkeley, including Gaieties (a musical written, composed, produced, and performed by the students of Ram’s Head Theatrical Society).
“Viennese Ball”: a formal ball with waltzes that was initially started in the 1970s by students returning from the now-closed Stanford in Vienna overseas program. It is now open to all students.
“Full Moon on the Quad”: An annual event at Main Quad, where students gather to kiss one another starting at midnight. Typically organized by the Junior class cabinet, the festivities include live entertainment, such as music and dance performances.
“Band Run”: An annual festivity at the beginning of the school year, where the band picks up freshmen from dorms across campus while stopping to perform at each location, culminating in a finale performance at Main Quad.
“Mausoleum Party”: An annual Halloween Party at the Stanford Mausoleum, the final resting place of Leland Stanford Jr. and his parents. A 20-year tradition, the “Mausoleum Party” was on hiatus from 2002 to 2005 due to a lack of funding, but was revived in 2006. In 2008, it was hosted in Old Union rather than at the actual Mausoleum, because rain prohibited generators from being rented. In 2009, after fundraising efforts by the Junior Class Presidents and the ASSU Executive, the event was able to return to the Mausoleum despite facing budget cuts earlier in the year.
Former campus traditions include the “Big Game bonfire” on Lake Lagunita (a seasonal lake usually dry in the fall), which was formally ended in 1997 because of the presence of endangered salamanders in the lake bed.

Award laureates and scholars

Stanford’s current community of scholars includes:

19 Nobel Prize laureates (as of October 2020, 85 affiliates in total)
171 members of the National Academy of Sciences
109 members of National Academy of Engineering
76 members of National Academy of Medicine
288 members of the American Academy of Arts and Sciences
19 recipients of the National Medal of Science
1 recipient of the National Medal of Technology
4 recipients of the National Humanities Medal
49 members of American Philosophical Society
56 fellows of the American Physics Society (since 1995)
4 Pulitzer Prize winners
31 MacArthur Fellows
4 Wolf Foundation Prize winners
2 ACL Lifetime Achievement Award winners
14 AAAI fellows
2 Presidential Medal of Freedom winners

Stanford University Seal