Monday, February 29, 2016
Brown Gymnasium – Scott Brown Gymnasium

Animal magnetism

Thursday, May 26, 2016
Avery House – Avery House

The Mentoring Effect: Conference on Mentoring Undergraduate Researchers

Tuesday, April 12, 2016
Center for Student Services 360 (Workshop Space) – Center for Student Services

TA Workshop: Getting the Biggest ‘Bang for Your Buck’ - Teaching strategies for busy TAs

Living—and Giving—the Caltech Dream

Growing up in Tehran, Iran, Mory Gharib (PhD '83) attended large, crowded schools. He was the kid who always raised his hand in class and asked tough questions. He craved one-on-one time with his teachers, which seldom came to pass.

So when the young Gharib read a newspaper article about a school in California with a three-to-one student-faculty ratio, it seemed almost unimaginable. Over the years, though, that school—Caltech—remained in his thoughts.

Years later, Gharib finally made it to Caltech as a graduate student. Since that time, he has built a distinguished career as a  researcher, mentor, inventor, entrepreneur, leader, and benefactor. And he has continued to search for the answers to tough questions.

"I couldn't have done this anywhere else," he says, referring to his career. "Caltech took care of me, and I have to take care of it."

In appreciation for the opportunities Caltech afforded him, Gharib—who currently serves as the Hans W. Liepmann Professor of Aeronautics and Bioinspired Engineering, director of Caltech's Graduate Aerospace Laboratories, and vice provost—has created an endowed fellowship fund to support new generations of Caltech graduate students.

Read the full story on the Caltech Giving website.

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Monday, March 28, 2016 to Friday, April 15, 2016
Center for Student Services 360 (Workshop Space) – Center for Student Services

Spring TA Training -- 2016

An Up-Close View of Bacterial "Motors"

Bacteria are the most abundant form of life on Earth, and they are capable of living in diverse habitats ranging from the surface of rocks to the insides of our intestines. Over millennia, these adaptable little organisms have evolved a variety of specialized mechanisms to move themselves through their particular environments. In two recent Caltech studies, researchers used a state-of-the-art imaging technique to capture, for the first time, three-dimensional views of this tiny complicated machinery in bacteria.

"Bacteria are widely considered to be 'simple' cells; however, this assumption is a reflection of our limitations, not theirs," says Grant Jensen, a professor of biophysics and biology at Caltech and an investigator with the Howard Hughes Medical Institute (HHMI). "In the past, we simply didn't have technology that could reveal the full glory of the nanomachines—huge complexes comprising many copies of a dozen or more unique proteins—that carry out sophisticated functions."

Jensen and his colleagues used a technique called electron cryotomography to study the complexity of these cell motility nanomachines. The technique allows them to capture 3-D images of intact cells at macromolecular resolution—specifically, with a resolution that ranges from 2 to 5 nanometers (for comparison, a whole cell can be several thousand nanometers in diameter). First, the cells are instantaneously frozen so that water molecules do not have time to rearrange to form ice crystals; this locks the cells in place without damaging their structure. Then, using a transmission electron microscope, the researchers image the cells from different angles, producing a series of 2-D images that—like a computed tomography, or CT, scan—can be digitally reconstructed into a 3-D picture of the cell's structures. Jensen's laboratory is one of only a few in the entire world that can do this type of imaging.

In a paper published in the March 11 issue of the journal Science, the Caltech team used this technique to analyze the cell motility machinery that involves a structure called the type IVa pilus machine (T4PM). This mechanism allows a bacterium to move through its environment in much the same way that Spider-Man travels between skyscrapers; the T4PM assembles a long fiber (the pilus) that attaches to a surface like a grappling hook and subsequently retracts, thus pulling the cell forward.

Although this method of movement is used by many types of bacteria, including several human pathogens, Jensen and his team used electron cryotomography to visualize this cell motility mechanism in intact Myxococcus xanthus—a type of soil bacterium. The researchers found that the structure is made up of several parts, including a pore on the outer membrane of the cell, four interconnected ring structures, and a stemlike structure. By systematically imaging mutants, each of which lacked one of the 10 T4PM core components, and comparing these mutants with normal M. xanthus cells, they mapped the locations of all 10 T4PM core components, providing insights into pilus assembly, structure, and function.

"In this study, we revealed the beautiful complexity of this machine that may be the strongest motor known in nature. The machine lets M. xanthus, a predatory bacterium, move across a field to form a 'wolf pack' with other M. xanthus cells, and hunt together for other bacteria on which to prey," Jensen says.

Another way that bacteria move about their environment is by employing a flagellum—a long whiplike structure that extends outward from the cell. The flagellum is spun by cellular machinery, creating a sort of propeller that motors the bacterium through a substrate. However, cells that must push through the thick mucus of the intestine, for example, need more powerful versions of these motors, compared to cells that only need enough propeller power to travel through a pool of water.

In a second paper, published in the online early edition of the Proceedings of the National Academy of Sciences (PNAS) on March 14, Jensen and his colleagues again used electron cryotomography to study the differences between these heavy-duty and light-duty versions of the bacterial propeller. The 3-D images they captured showed that the varying levels of propeller power among several different species of bacteria can be explained by structural differences in these tiny motors.

In order for the flagellum to act as a propeller, structures in the cell's motor must apply torque—the force needed to cause an object to rotate—to the flagellum. The researchers found that the high-power motors have additional torque-generating protein complexes that are found at a relatively wide radius from the flagellum. This extra distance provides greater leverage to rotate the flagellum, thus generating greater torque. The strength of the cell's motor was directly correlated with the number of these torque-generating complexes in the cell.

"These two studies establish a technique for solving the complete structures of large macromolecular complexes in situ, or inside intact cells," Jensen says. "Other structure determination methods, such as X-ray crystallography, require complexes to be purified out of cells, resulting in loss of components and possible contamination. On the other hand, traditional 2-D imaging alone doesn't let you see where individual protein pieces fit in the complete structure. Our electron cryotomography technique is a good solution because it can be used to look at the whole cell, providing a complete picture of the architecture and location of these structures."

The work involving the type IVa pilus machinery was published in a Science paper titled "Architecture of the type IVa pilus machine." First author Yi-Wei Chang is a research scientist at Caltech; additional coauthors include collaborators from the Max Planck Institute for Terrestrial Microbiology, in Marburg, Germany, and from the University of Utah. The study was funded by the National Institutes of Health (NIH), HHMI, the Max Planck Society, and the Deutsche Forschungsgemeinschaft.

Work involving the flagellum machinery was published in a PNAS paper titled "Diverse high-torque bacterial flagellar motors assemble wider stator rings using a conserved protein scaffold." Additional coauthors include collaborators from Imperial College London; the University of Texas Southwestern Medical Center; and the University of Wisconsin–Madison. The study was supported by funding from the UK's Biotechnology and Biological Sciences Research Council and from HHMI and NIH.

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Quintessentially Caltech

How best to recognize Caltech's own Ahmed Zewail, the Linus Pauling Professor of Chemistry and professor of physics, and director of the Physical Biology Center for Ultrafast Science and Technology, who has served on Caltech's faculty for 40 years? President Thomas F. Rosenbaum had the answer: what he would later call a "quintessentially Caltech conference."

And so, on Friday, February 26, more than 1,000 people gathered to hear exceptional researchers, including 5 Nobel Laureates, from across disciplines consider our future as part of the full-day "Science and Society" conference that honored the career of Zewail, whom Rosenbaum called "a wizard of scientific innovation."

Read the full story and view the slideshow

Written by Alex Roth

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Caltech: A Personal Perspective

Ahmed Zewail, Nobel Laureate
Linus Pauling Professor of Chemistry and Professor of Physics, Caltech

Zewail provided an overview of his journey from a young child in Egypt to Caltech Nobel laureate. On the day he won the 1999 Nobel Prize in Physics, he recalled, Caltech president David Baltimore came to Zewail's house, but he refused to open the door. "We thought he was paparazzi," Zewail admitted.

Credit: Chris Sabanpan

The End of Disease?

Roger Kornberg, Nobel Laureate
Mrs. George A. Winzer Professor in Medicine, Stanford, School of Medicine

As advanced as we think we are, Kornberg said, scientists today understand less than 1 percent of human biology. Attracting more young people to the field of medical research is therefore critical. "Young scientists are the most likely to discover something," he said. "And numbers matter."

Credit: Chris Sabanpan

The Future of Medicine

David Baltimore, Nobel Laureate
Caltech President Emeritus
Robert Andrews Millikan Professor of Biology, Caltech

The human body can survive a maximum of roughly 120 years, according to Baltimore. He predicted a future in which scientists work to push that envelope, using gene editing "to liberate us from the process of aging" and "to perfect the human body, whatever that means."

Credit: Chris Sabanpan

The Future of Quantum Physics

H. Jeff Kimble, Member, National Academy of Sciences
William L. Valentine Professor and Professor of Physics, Caltech

Kimble's lecture about the future of quantum physics included predictions about quantum computing, quantum simulation, and quantum metrology. "Science helps hold us together and appreciate our sameness rather than our differences," he said.

 

Credit: Chris Sabanpan

Time, Einstein, and the Coolest Stuff in the Universe

William Phillips, Nobel Laureate
Physicist, National Institute of Standards and Technology
Distinguished University Professor, University of Maryland

In a hands-on demonstration, Phillips put on a pair of lab goggles and dunked a variety of items—a rose, a racquetball, several inflated balloons—into a vat of liquid nitrogen to help demonstrate his overall point: that we can create super-accurate atomic clocks by cooling down atoms to astoundingly low temperatures.

Credit: Chris Sabanpan

Inequality and World Economics

A. Michael Spence, Nobel Laureate
Philip H. Knight Professor and Dean, Emeritus
Stanford University Graduate School of Business

Spence discussed a number of global economic trends—including the decline in middle-class jobs and the rise of job-eliminating technologies—in a lecture that considered the disparities between rich and poor. "I'm a little worried about what's going on in the global economy right now and I tend to be an optimist," he said.

Credit: Chris Sabanpan

The Future of Space Exploration

Charles Elachi, NASA Outstanding Leadership Medal Recipient
Caltech Vice President
Director, Jet Propulsion Laboratory

Elachi said he believes we will establish a space station on Mars and that humans will begin visiting the planet by 2030. But, he noted, "It's important that we take care of our own planet. It's the only thing we have, at least for now."

 

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How best to recognize Caltech's own Ahmed Zewail, the Linus Pauling Professor of Chemistry and professor of physics, and director of the Physical Biology Center for Ultrafast Science and Technology, who has served on Caltech's faculty for 40 years? President Thomas F. Rosenbaum had the answer: what he would later call a "quintessentially Caltech conference."

And so, on Friday, February 26, more than 1,000 people gathered to hear exceptional researchers, including 5 Nobel Laureates, from across disciplines consider our future as part of the full-day "Science and Society" conference that honored the career of Zewail, whom Rosenbaum called "a wizard of scientific innovation."

The speakers lectured on a broad spectrum of topics, ranging from space travel to global economic inequality to what happens when five inflated balloons are stuffed into a vat of liquid nitrogen. Their talks were moderated by Nathan Gardels, editor in chief of The WorldPost, and Peter Dervan, the Bren Professor of Chemistry, who noted while introducing Zewail that they have been close friends ever since their early days starting as assistant professors together at Caltech.

"What an extraordinary day," Rosenbaum said at the conclusion of the event, held in Beckman Auditorium. "It's unusual to find a series of talks at this incredibly high level of excellence—intellectually deep and pedagogically engaging."

As many of the speakers pointed out, Zewail's list of accomplishments is staggering. He has authored some 600 articles and 16 books and was sole recipient of the 1999 Nobel Prize for his pioneering work in femtochemistry. In the post-Nobel era, he developed a new field dubbed four-dimensional electron microscopy. He has been active in global affairs, serving as the first U.S. Science Envoy to the Middle East and helping establish the Zewail City of Science and Technology in Cairo, which he hopes to turn into "the Caltech of Egypt."

"Ahmed is a very special kind of scientist," said Fiona Harrison, chair of Caltech's Division of Physics, Mathematics and Astronomy, during the conference's introductory remarks. She noted the "incredible breadth of his research" and cited a colleague's observation that "Ahmed is someone who never has average goals."

Jackie Barton, chair of Caltech's Division of Chemistry and Chemical Engineering, praised Caltech for taking a chance on Zewail four decades ago, when he was a young scientist. "He had this vision," she said. "The vision was to watch the dynamics of chemical reactions, to watch reactions happening on a faster and faster time scale, indeed to watch the making and breaking of chemical bonds."

She added: "He has this intuitive sense of the dynamical motions of atoms and molecules, their coherence, or lack thereof, as the case may be. And then he has this extraordinary attention to every detail, so that he's able to meld together theory and experiment and understand that dance, that choreography of atoms and molecules as they carry out a reaction."

To further honor Zewail, Caltech presented him with a rare book of Benjamin Franklin's speeches and scientific research—on lightning rods and the aurora borealis, among other phenomena—that is signed by Rosenbaum and all of Caltech's former presidents. Caltech Provost Ed Stolper noted that it is the only book authored by Franklin that was published during his lifetime.

As Stolper noted in his introductory remarks, the gift is a fitting one for Zewail, who has come to embody the ideal of Caltech, a place "where scientists and engineers are limited only by their imagination." He added Ahmed is one of the few scientists that, like Benjamin Franklin and Linus Pauling, not only excelled in science but has made a broader impact on society through his writings and actions.

Written by Alex Roth

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Rothenberg Wins Feynman Prize

The 2016 Richard P. Feynman Prize for Excellence in Teaching has been awarded to Ellen Rothenberg, the Albert Billings Ruddock Professor of Biology.

Established in 1993, the Feynman Prize annually honors "a professor who demonstrates, in the broadest sense, unusual ability, creativity, and innovation in undergraduate and graduate classroom or laboratory teaching." Rothenberg, who has been at Caltech since joining the faculty as an assistant professor in 1982, was nominated for the prize by her students, who cited qualities such as her passion for teaching and her engagement with students as the reason for their nominations.

Rothenberg investigates the regulatory mechanisms that control blood stem cell differentiation and the development of T lymphocytes—white blood cells that play an important role in immunity. Not surprisingly, when she began at Caltech, her first teaching assignment was Immunology (Bi 114), a course that she continued to teach for 25 years, consistently receiving high ratings from her students in her teaching-quality feedback reports. In 1989, Rothenberg also introduced Caltech's first course on the molecular biology of blood development, Hematopoiesis: A Developmental System (Bi 214)—a course that she still teaches every other year.

Rothenberg recently was instrumental to changes made to the introductory biology courses at Caltech. "I was the chair of the Curriculum Committee, and I noticed that there were issues that arose for both students and faculty with the first two introductory courses," she says. Beginning in 2008, she began redeveloping and teaching these introductory courses, Cell Biology (Bi 9) and then molecular biology (Bi 8). A student's first two terms at Caltech are mandatory pass/fail, "and we discovered that the students are actually really excited to do something hard when it's on a pass/fail basis," she explains.

In a letter of nomination, one of Rothenberg's students said that she appreciated the challenge to learn more complicated material in an introductory course. "In her course, Professor Rothenberg emphasizes important concepts about molecular biology; however, she also takes time to explore higher-level concepts with incredible enthusiasm," the student said. "This introduced me to the many complex systems I could learn about while showing me how exciting biological research is. I also sit on the Curriculum Committee, which she leads, and I have seen how she constantly returns to the idea of what will help students learn best and what will train them effectively."

Another student who nominated Rothenberg wrote that "… she showed students that, contrary to what they might have heard, biology was not simply a 'memorization game,' but rather a logic puzzle. By slowly introducing us to different research techniques, she allowed us to see how we could pose and answer questions in biology ourselves."

In addition to challenging her students to learn in a new way, Rothenberg says that these introductory courses also challenged her to teach differently. Because introductory courses have larger class sizes, she says it was inherently more difficult to get to know her students. So, she found ways to connect with her students outside of class time. "She spends a lot of time with her students," one student said in a nomination, "even actively participating in recitation sections with her TAs, an unusual task for professors. She strives to improve her class every year."

Previously, Rothenberg was awarded the Biology Undergraduate Students Advisory Council Award for excellence in teaching four times, the Ferguson Prize for Undergraduate Teaching twice, and the ASCIT Award for Undergraduate Teaching twice. In addition, she has chaired the divisional Curriculum Committee for the past several years, working to rationalize the biology curriculum and to put the best teachers in place for each course. As part of her work on the Curriculum Committee, she interacts closely with the Biology Undergraduate Students Advisory Council.

"Winning this award and being recognized at an institutional level…it means a lot to me. And I'm also really humbled that I'm the first biologist ever to get the Feynman Prize," she says. "I love teaching. The greatest gift you can give someone is to share your understanding with them and to help them develop their own understanding. That incredible connection between the way you appreciate the complexity of the world and the way you can give students the tools to see things that you never saw before—it's really beautiful. And the fact that this institute has a way of valuing that is really wonderful," she adds.

The Feynman Prize has been endowed through the generosity of Caltech Associates Ione and Robert E. Paradise and an anonymous local couple. Some of the most recent winners of the Feynman Prize include Kevin Gilmartin, professor of English; Steven Frautschi, professor of theoretical physics, emeritus; and Paul Asimow, professor of geology and geochemistry.

Nominations for next year's Feynman Prize for Excellence in Teaching will be solicited in the fall. Further information about the prize can be found on the Provost's Office website.

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The 2016 Richard Feynman Prize for Excellence in Teaching has been awarded to Ellen Rothenberg, the Albert Billings Ruddock Professor of Biology.

Learning to Program Cellular Memory

What if we could program living cells to do what we would like them to do in the body? Having such control—a major goal of synthetic biology—could allow for the development of cell-based therapies that might one day replace traditional drugs for diseases such as cancer. In order to reach this long-term goal, however, scientists must first learn to program many of the key things that cells do, such as communicate with one another, change their fate to become a particular cell type, and remember the chemical signals they have encountered.

Now a team of researchers led by Caltech biologists Michael Elowitz, Lacramioara Bintu, and John Yong (PhD '15) have taken an important step toward being able to program that kind of cellular memory using tools that cells have evolved naturally. By combining synthetic biology approaches with time-lapse movies that track the behaviors of individual cells, they determined how four members of a class of proteins known as chromatin regulators establish and control a cell's ability to maintain a particular state of gene expression—to remember it—even once the signal that established that state is gone.

The researchers reported their findings in the February 12 issue of the journal Science.

"We took some of the most important chromatin regulators for a test-drive to understand not just how they are used naturally, but also what special capabilities each one provides," says Elowitz, a professor of biology and bioengineering at Caltech and an investigator with the Howard Hughes Medical Institute (HHMI). "We're playing with them to find out what we can get them to do for us."

Rather than relying on a single protein to program all "memories" of gene expression, animal cells use hundreds of different chromatin regulators. These proteins each do basically the same thing—they modify a region of DNA to alter gene expression. That raises the question, why does the cell need all of these different chromatin regulators? Either there is a lot of redundancy built into the system or each regulator actually does something unique. And if the latter is the case, synthetic biologists would like to know how best to use these regulators as tools—how to select the ideal protein to achieve a certain effect or a specific type of cellular memory.

Looking for answers, the researchers turned to an approach that Elowitz calls "build to understand." Rather than starting with a complex process and trying to pick apart its component pieces, the researchers build the targeted biological system in cells from the bottom up, giving themselves a chance to actually watch what happens with each change they introduce.

In this case, that meant sticking different chromatin regulators—four gene-silencing proteins—down onto a specific section of DNA and seeing how each behaved. In order to do that the researchers engineered cells so that adding a small molecule would cause one of the gene-silencing regulators to bind to DNA near a particular gene that codes for a fluorescent protein. By tracking fluorescence in individual cells, the researchers could readily determine whether the regulator had turned off the gene. The researchers could also release the regulator from the DNA and see how long the gene remembered its effect.

Although there are hundreds of chromatin regulators, they can be categorized into about a dozen broader classes. For this study, the researchers tested regulators from four biochemically diverse classes.

"We tried a variety to see if different ones give you different types of behavior," explains Bintu. "It turns out they do."

For a month at a time, the researchers used microscopy or flow cytometry to observe the living cells, using cell-tracking software that they wrote and time-lapse movies to watch individual cells grow and divide. In some cases, after a regulator was released, the cells and their daughter cells remained dark for days and then lit back up, indicating that they remembered the modification transiently. In other cases, the cells never lit back up, indicating more permanent memory.

After modification, the genes were always in one of three states—"awake" and actively making protein, "asleep" and inactive but able to wake up in a matter of days, or "in a coma" and unable to be awakened within 30 days. Within an individual cell, the genes were always either completely on or off.

That led the researchers to the surprising finding that the regulators control not the level or degree of expression of a particular gene in an individual cell, but rather how many cells in a population have that gene on or off.

"You're controlling the probability that something is on or off," says Elowitz. "We think that this is something that's very useful generally in a multicellular organism—that in many cases, the organism may want to tell cells, 'I just want 30 percent of you to differentiate. You don't all need to do it.' This chromatin regulation system seems ready-made for orders like those."

In addition, the researchers found that the type of memory imparted by each of the four chromatin regulators was different. One produced permanent memory, turning off the gene and putting a fraction of cells into a coma for the full 30 days. One yielded short-term memory, with the cells immediately waking up. "The really interesting thing we found is that some of the regulators give this type of hybrid memory where some of the cells awaken while a fraction of the cells remain in a deep coma," says Bintu. "How many are in the coma depends on how long you gave the signal—how long the chromatin regulator stayed attached."

Going forward, the group plans to study additional chromatin regulators in the same manner, developing a better sense of the many ways they are used in the cell and also how they might work in combination. In the longer term they want to put these proteins together with other cellular components and begin programming more complex developmental behavior in synthetic circuits.

"This is a step toward realizing this emerging vision of programmable cell-based therapies," says Elowitz. "But we are also answering more basic research questions. We see these as two sides of the same coin. We're not going to be able to program cells effectively until we understand what capabilities their core pathways provide. "

Additional Caltech authors on the paper, "Dynamics of epigenetic regulation at the single-cell level," include Yaron E. Antebi and Kayla McCue (BS '15). Yasuhiro Kazuki, Narumi Uno, and Mitsuo Oshimura of Tottori University in Japan are also coauthors. The work was supported by the Defense Advanced Research Projects Agency, the Human Frontier Science Program, the Jane Coffin Childs Memorial Fund for Medical Research, the Beckman Institute at Caltech, the Burroughs Wellcome Fund, and HHMI.

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Combining synthetic biology approaches with time-lapse movies, biologists have determined how some proteins shape a cell's ability to remember signals.

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