Screening Cells for a Cure

A powerful partnership leads to advances in islet-cell transplants to treat diabetes

Living with type 1 diabetes today is typically manageable thanks to advancements in medical technology. However, some patients still confront severe complications, from extreme hypoglycemia that can lead to diabetic coma to long-term effects, such as blindness, nerve damage, and kidney failure. In some cases, type 1 diabetes can be life-threatening, and in all cases, it is currently incurable.

But there is hope, fostered by a collaboration between Caltech and its neighbor in Duarte, City of Hope. Established in 2008 with a $6 million gift from an anonymous donor, the Caltech-City of Hope Biomedical Research Initiative provides seed grants to accelerate the development of basic scientific research and its translation into applications ranging from new pharmaceuticals to medical devices to treatment methods. The partnership was formalized—and further strengthened—in 2014, when the two institutions signed a memorandum of understanding, encouraging researchers to collaborate and share resources.

Leadership from Caltech and City of Hope and members of the public celebrated the partnership at a special event on May 13. More than 70 attendees gathered in Caltech's Beckman Institute Auditorium to learn about progress in fighting diabetes.

"The benefits of the deepening relationship between our two institutions emerged clearly in the evening's events," says Caltech President Thomas F. Rosenbaum, holder of the Sonja and William Davidow Presidential Chair and professor of physics. "Our increasing set of research interactions is making great strides in translating fundamental science to advance human health."

To date, the initiative has funded 28 endeavors led by teams of Caltech and City of Hope investigators—early-stage research projects that might not have moved forward if they had had to rely on traditional funding sources.

"The more we work together, the more we enable discovery," says City of Hope president and CEO Robert Stone. "Saving lives today and tomorrow—that's what this collaboration is about."

One encouraging development for people facing uncontrolled type 1 diabetes comes in the form of a simple surgery. The procedure takes healthy, functioning pancreatic islets—clusters of cells that contain insulin-producing beta cells—from an organ donor and transplants them into a patient's liver. Doctors at City of Hope have already performed the surgery on a limited number of patients and have seen promising results.

While islet transplantation eventually may lead to a cure for diabetes, challenges remain in making it practical. Once islets have been donated, for example, how can they be isolated and kept functional? How do researchers distinguish good islets from bad without wasting the good ones during testing?

Through the Caltech-City of Hope Biomedical Research Initiative, researchers and clinicians are working hand-in-hand to answer these important questions.

At the event, researchers told the story and explained the science behind their project. Fouad Kandeel, chair and professor in the Department of Clinical Diabetes, Endocrinology, and Metabolism at City of Hope, and his colleague, Kevin Ferreri, associate research professor in the Division of Developmental and Translational Diabetes and Endocrine Research, have been working on islet cell transplantation as a treatment for their patients with type 1 diabetes. Yet existing methods of selecting islets took too much time, involved too much labor, and used up too many islets.

That is where the Caltech partners came in. Yu-Chong Tai, the Anna L. Rosen Professor of Electrical Engineering and Mechanical Engineering, and Hyuck Choo, assistant professor of electrical engineering and medical engineering, invented a novel device that can screen individual islets. The microfluidic platform accurately determines the health of an islet sample by applying glucose and measuring the sample's reaction. In less than a year, the team has designed a proof-of-concept platform.

Once the device is perfected, Choo believes the team will be able to easily scale it up and even use its technology to help overcome other clinical challenges.

"This is the perfect opportunity for medical engineering at Caltech," says Choo. "We want to create technology-based solutions to large-scale societal health issues, like diabetes."

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Spotlight on Graduate Research

It is no secret that Caltech's graduate students have unparalleled research opportunities. Working closely with faculty advisers and colleagues in diverse fields across campus, their contributions are essential to the Institute's advances in science, engineering, and technology. For nearly two decades, the Everhart Lecture Series has provided a venue to highlight graduate student research at Caltech.

The annual series, named after Caltech president emeritus Tom Everhart, provides three carefully selected graduate students with an opportunity to present their work to an Institute-wide audience. The series was established with the goal of "encouraging interdisciplinary interaction and helping faculty and graduate students across campus to share ideas about recent research developments, problems and controversies, and to recognize the exemplary presentation and research abilities of Caltech's graduate students."

"Having the ability to demonstrate your work to the broader community—those outside of your own scientific area—is extremely important, and too often graduate students have very little experience with this," says graduate student Constantine Sideris, the 2014–15 chair of the Everhart Lecture Series committee, an interdisciplinary committee of graduate students that selects the three graduate student lecturers from a pool of more than a dozen applicants each fall.

"This series allows them to hone their presentation and dynamic speaking skills, and also their ability to explain difficult, technical concepts to a diverse audience," Sideris says.

This year's lecturers—Carissa Eisler (chemistry and chemical engineering), Roarke Horstmeyer (electrical engineering), and Peter Rapp (chemistry and chemical engineering)—gave talks on campus earlier this spring, and all three were invited to share their work with members of the Caltech community during the Institute's annual Seminar Day event in May. This year's lectures span a range of topics, from enhancing solar-cell efficiency, to improving microscope imaging, to understanding polymers. (Complete lecture descriptions from the students as well as links to podcasts of the recorded talks on iTunes U can be found below.)

"Research is only getting more interdisciplinary, so effectively communicating your work is an essential skill," says Eisler. "The lecture was really challenging, and I was very nervous, but it was incredibly rewarding, and I'm so glad that I did it."

Eisler and her colleagues noted that participating in the lectures provided valuable learning opportunities—by forcing them to synthesize and explain their work to individuals outside of their respective fields—and helped to build campus awareness for the breadth of research that's being done by graduate students.

"I work with a team of remarkable people, and I hope the lecture communicated that my project is just one among many exciting projects in our lab," Rapp says.  

 

Lecture Descriptions:

Building a Brighter Future: Spectrum-Splitting as a Pathway for 50% Efficiency Solar Cells
By Carissa Eisler
Lab: Harry Atwater, Howard Hughes Professor of Applied Physics and Materials Science and director of the Resnick Sustainability Institute

Although possible, ultra-high solar-cell efficiencies (>50 percent) have not been achieved because of limitations by current fabrication methods. Spectrum-splitting modules, or architectures that employ optical elements to divide the incident spectrum into different color bands, are promising because they can convert each photon more efficiently than traditional methods. This talk discusses our design and prototyping efforts to create such a spectrum-splitting module. We explore the spectrum-splitting optics and geometric optimizations in the context of high-efficiency designs. We show a design that achieves 50 percent efficiency with realistic device losses and geometric constraints. 

Listen to the lecture on iTunesU: https://itunes.apple.com/us/podcast/building-brighter-future-spectrum/id986954281?i=341029550&mt=2

 

Computational Microscopy: Turning Megapixels into Gigapixels
By Roarke Horstmeyer
Lab: Changhuei Yang, Professor of Electrical Engineering, Bioengineering, and Medical Engineering

Optical aberrations limit the size of current microscope images to tens of megapixels. This talk will present a method to boost a microscope's resolving power to one gigapixel using a technique termed Fourier ptychography. No moving parts or precision controls are needed for this resolution enhancement. The only required hardware is a standard microscope, which we outfit with a digital detector and an array of LEDs. An optimization algorithm does the rest of the work. Example applications of our new microscope include full-slide digital pathology imaging, wide-scale surface profile mapping of human blood, and achieving sub-wavelength resolution without needing oil immersion.

Listen to the lecture on iTunesU: https://itunes.apple.com/us/podcast/computational-microscopy-turning/id986954281?i=341030229&mt=2

 

Shaking Hands in a Crowded Room: How Sticky Polymers Travel through Viscoelastic Gels
By Peter Rapp
Lab: David Tirrell, Ross McCollum-William H. Corcoran Professor of Chemistry and Chemical Engineering; Director, Beckman Institute

What if you could give a polymer hands and feet and watch it move? We have developed biological approaches to synthesizing functional materials made from proteins, nature's flagship polymers. These approaches provide a set of tools for answering fundamental questions in polymer physics and for synthesizing dynamic materials that find applications in soft-tissue engineering and regenerative medicine. This talk will explore the dynamics of a model "sticky" polymer: an artificial protein engineered with associative endblocks that self-assembles into viscoelastic hydrogels. Fluorescence relaxation studies have demonstrated that polymer diffusion in these gels is controlled by endblock exchange, a process akin to a molecular handshake. Genetic approaches to modifying the endblock architecture enable tuning of polymer mobility over a wide range.

Listen to the lecture on iTunesU: https://itunes.apple.com/us/podcast/shaking-hands-in-crowded-room/id986954281?i=343195468&mt=2

 

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Amgen and Caltech Establish Partnership in Health Sciences

Caltech and Amgen have joined forces in the pursuit of foundational discoveries in the biological sciences through a multifaceted new partnership spanning research, graduate student training, and shared resources.

"The work we do is built upon the foundation of basic discoveries in biology," says Alexander Kamb (PhD '88), Amgen's senior vice president of Discovery Research. "We look forward to strengthening and extending this foundation through our connection with Caltech."

Caltech received its first gift from Amgen in 1981, just one year after the company was formed. Over the past three decades, Amgen has provided support for a variety of educational programs and investigations at Caltech. Today, Amgen has grown to be one of the world's leading independent biotechnology companies, and it has now entered into a collaborative research agreement for joint investigations with Caltech that will leverage the two institutions' strengths in discovery, and translational and clinical science.

Under the terms of the new agreement, Amgen will fund up to five research projects per year for three years. Bridging the divisions of Chemistry and Chemical Engineering, Biology and Biological Engineering, and Engineering and Applied Science, the projects will focus on large- and small-molecule drug discovery, drug-delivery devices, and diagnostic technologies. Amgen will also provide support for Amgen Graduate Student Fellows in Caltech's interdisciplinary Graduate Program in Biochemistry and Molecular Biophysics.

In addition to fellowship and research support, Amgen has chosen Caltech as its first partner to access the Amgen Biology-Enabling Resource, a searchable database comprising more than 1,000 items, including molecules, peptides, antibodies, and engineered cell lines acquired through years of discovery efforts. Amgen will have no claim to ownership of intellectual property to discoveries that may ensue. Over time, Amgen will extend access to other research institutions and, as specific materials are depleted, add others to the catalog.

This comprehensive agreement with Amgen exemplifies Caltech's commitment to building strategic partnerships to optimize the Institute's capabilities and help solve pressing problems for the benefit of the public. This and other such relationships with corporations, government agencies, non-governmental organizations, and other institutions, focus on transferring technology from Caltech's campus to industry.

"Each industry collaboration has a unique scope and focus, but all share a goal of transforming new research findings into applications that will benefit society," explains Caltech Vice Provost, Mory Gharib, the Hans W. Liepmann Professor of Aeronautics and Bioinspired Engineering. "The hope is that the Caltech–Amgen partnership will enable our teams to swiftly convert laboratory discoveries into therapeutics or devices that will improve patients' lives."

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Three Caltech Fulbrights

Caltech seniors Jonathan Liu, Charles Tschirhart, and Caroline Werlang will be engaging in research abroad as Fulbright Scholars this fall. Sponsored by the Department of State's Bureau of Educational and Cultural Affairs, the Fulbright Program was established in 1946 to honor the late Senator J. William Fulbright of Arkansas for his contributions to fostering international understanding.

 

 

Jonathan Liu is an applied physics major from Pleasanton, California, who will be doing research at Ludwig Maximilian University Munich in Germany. He plans to work with a biophysicist studying how DNA moves in a liquid with a thermal gradient, which could shed light on the molecular origins of life. Long strands of DNA should break apart well before they have time to organize themselves into the complicated arrangements needed to be self-reproducing, but previous work in the lab Liu is joining has hinted that deep-sea hydrothermal vents may have allowed long strands to form stable clusters. Liu plans to enroll at UC Berkeley for graduate study in physics at the PhD level on his return; he was awarded one of UC Berkley's Graduate Student Instructorships to support his work.

Charles Tschirhart of Naperville, Illinois, is a double major in applied physics and chemistry. He will be studying condensed matter physics at the University of Nottingham, England, where he plans to develop new ways to "photograph" nanometer-sized (billionth-of-a-meter-sized) objects using atomic force microscopy. He will then proceed to UC Santa Barbara to earn a PhD in experimental condensed matter physics. Charles has won both a Hertz fellowship and National Science Foundation Graduate Research Fellowship; both will support his PhD work at UC Santa Barbara.

Caroline Werlang, a chemical engineering student from Houston, Texas, will go to the Institute of Bioengineering at the École Polytechnique Fédérale de Lausanne in Switzerland to work on kinases, which are proteins that act as molecular "on/off" switches. She will join a lab that is trying to determine how kinases select and bind to their targets in order to initiate or block other biological processes—an important step toward designing a synthetic kinase that could activate a tumor-suppressor protein, for example. After her Fulbright, she will pursue a doctorate in biological engineering at MIT. Caroline's PhD studies will be supported by a National Science Foundation Graduate Fellowship.

The Fulbright Program is the flagship international exchange program sponsored by the U.S. government. Seniors and graduate students who compete in the U.S. Fulbright Student Program can apply to one of the more than 160 countries whose universities are willing to host Fulbright Scholars. For the academic program, which sponsors one academic year of study or research abroad after the bachelor's degree, each applicant must submit a plan of research or study, a personal essay, three academic references, and a transcript that demonstrates a record of outstanding academic work.

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Tuesday, May 26, 2015 to Friday, May 29, 2015
Center for Student Services 360 (Workshop Space) – Center for Student Services

CTLO Presents Ed Talk Week 2015

Ditch Day? It’s Today, Frosh!

Today we celebrate Ditch Day, one of Caltech's oldest traditions. During this annual spring rite—the timing of which is kept secret until the last minute—seniors ditch their classes and vanish from campus. Before they go, however, they leave behind complex, carefully planned out puzzles and challenges—known as "stacks"—designed to occupy the underclassmen and prevent them from wreaking havoc on the seniors' unoccupied rooms.

Follow the action on Caltech's Facebook, Twitter, and Instagram pages as the undergraduates tackle the puzzles left for them to solve around campus. Join the conversation by sharing your favorite Ditch Day memories and using #CaltechDitchDay in your tweets and postings.

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Caltech Students Named Goldwater Scholars

Two Caltech students, Saaket Agrawal and Paul Dieterle, have been awarded Barry M. Goldwater scholarships for the 2015–16 academic year.

The Barry Goldwater Scholarship and Excellence in Education Program was established by Congress in 1986 to award scholarships to college students who intend to pursue research careers in science, mathematics, and engineering.

Saaket Agrawal is a sophomore from El Dorado Hills, California, majoring in chemistry. Under Greg Fu, the Altair Professor of Chemistry, Agrawal works on nickel-catalyzed cross coupling, a powerful method for making carbon-carbon bonds. Specifically, Agrawal conducts mechanistic studies on these reactions, which involves elucidating the pathway through which they occur. After Caltech, he plans to pursue a PhD research program in organometallic chemistry—the combination of organic (carbon-based) and inorganic chemistry—and ultimately hopes teach at the university level.

"Caltech is one of the best places in the world to study chemistry. The faculty were so willing to take me on, even as an undergrad, and treat me like a capable scientist," Agrawal says. "That respect, and the ability to do meaningful work, has motivated me."

Paul Dieterle is a junior from Madison, Wisconsin, majoring in applied physics. He works with Oskar Painter, the John G. Braun Professor of Applied Physics, studying quantum information science.

"The quantum behavior of atoms has been studied for decades. We are researching the way macroscopic objects behave in a quantum mechanical way in order to manipulate them into specific quantum states," Dieterle says. Painter's group is studying how to use macroscopic mechanical objects to transform quantized electrical signals into quantized optical signals as part of the larger field of quantum computing, a potential next generation development in the field.

"The power of quantum computing would be immense," says Dieterle, who would like to attend graduate school to study quantum information science. "We could simulate incredibly complex things, like particles at the edge of a black hole. Participating in this physics revolution is so exciting."

Agrawal and Dieterle bring the number of Caltech Goldwater Scholars to 22 in the last decade.

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Barton Receives Highest Honor from American Institute of Chemists

The Gold Medal of the American Institute of Chemists (AIC) has been awarded to Jacqueline Barton, the Arthur and Marian Hanisch Memorial Professor of Chemistry and chair of the Division of Chemistry and Chemical Engineering. The award is the AIC's highest honor and recognizes "service to the science of chemistry and to the profession of chemist or chemical engineer in the United States."

Barton's research centers on the chemical and physical properties of DNA and their biological implications. Her group examines the chemistry of how electrons are conducted throughout a DNA molecule and how DNA-repairing enzymes can use this electron flow to locate mutations and mistakes in the DNA that could potentially cause cancers and diseases.

Barton received her PhD from Columbia University in 1978. She has been at Caltech as a professor since 1989. The recipient of numerous honors—including the 2010 National Medal of Science, a MacArthur Fellowship, and the National Science Foundation's Waterman Award—Barton also was awarded the 2015 Priestley Medal, the highest honor of the American Chemical Society, for her work on the chemistry of DNA.

 

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Monday, May 18, 2015
Brown Gymnasium – Scott Brown Gymnasium

Jupiter’s Grand Attack

John H. Richards, 1930–2015

John H. ("Jack") Richards, a professor of organic chemistry and biochemistry at Caltech whose research was focused on gaining a molecular understanding of the mechanisms of protein function, passed away on Thursday, April 23, 2015. He was 85 years old.

Richards used altered proteins obtained from the deliberate mutation of DNA—a process called site-directed mutagenesis—in combination with recombinant and cloning techniques, as well as chemically synthesized polypeptides (chains of amino acids) and their derivatives, to study the mechanisms by which proteins act as catalysts to perform the chemical reactions necessary to life. Among the proteins of particular interest to Richards were proteolytic enzymes that break apart other proteins; enzymes called lactamases that endow some microorganisms with antibiotic resistance; and DNA polymerases, the enzymes that build DNA molecules by assembling nucleotides.

Richards also worked in collaboration with Harry Gray, the Arnold O. Beckman Professor of Chemistry, and Jay Winkler, member of the Beckman Institute and faculty associate in chemistry, examining how proteins transport the electrons that are the cell's energy currency, including a class of copper-containing proteins called azurins that power certain types of bacteria. As Gray recalls, "Jack, Jay Winkler, and I worked closely together for over 25 years. He was the perfect collaborator, generous with his time. He taught Jay and me and our students the biology we needed to attack problems in biological inorganic chemistry. His work on engineering blue copper proteins opened the way for experiments in the Beckman Institute Laser Resource Center that shed light on the factors that control electron flow in respiration and photosynthesis."

According to colleague Douglas Rees, the Roscoe Gilkey Dickinson Professor of Chemistry at Caltech and an investigator with Howard Hughes Medical Institute, Richards was a "visionary" who helped drive the integration of chemistry and biology at the heart of contemporary biochemistry.

"What most struck me about Jack is he had this real style," Rees recalls. "He wasn't the sort of guy who was just going to crank through and try to wear some problem down. He liked coming up with a really clever, elegant solution to a problem. And early on, at a time when I think a lot of chemists were typically not very interested in biological problems, Jack had this fascination with biology and chemical mechanisms. He appreciated how the future of biology was rooted in chemistry, and he was the leader of the modern era of biochemistry in the chemistry division here."

Richards was born on March 13, 1930, in Berkeley, California, and earned a BA from UC Berkeley in 1951. As a Rhodes Scholar, he traveled to England to attend the University of Oxford, from which he obtained a BSc in 1953. He then returned to UC Berkeley for his graduate studies, earning a PhD in 1955.

After two years as an instructor at Harvard University, Richards came to Caltech in 1957 as an assistant professor. He spent the rest of his career at the Institute, with promotions to associate professor in 1961 and to professor in 1970. He was named a professor of organic chemistry and biochemistry in 1999. Richards was the chair of the faculty from 1991 to 1993. 

"Jack Richards was part of the fabric of Caltech and interdisciplinary science for more than 50 years," says Jacqueline K. Barton, the Arthur and Marian Hanisch Memorial Professor and chair of the Division of Chemistry and Chemical Engineering.

Over his career, Richards also served in a number of corporate and governmental advisory roles, including as a member of the board of the Huntington Medical Research Institute since 1999 and as a member of the Department of Energy's Basic Energy Science Advisory Committee (2001–13).

From 1985 to 2007, Richards was a corporate scientific adviser to the biotechnology company Applied Biosystems, now a part of Life Technologies. Applied Biosystems was the first company to commercially produce an automated DNA sequencing instrument—technology that was pioneered at Caltech by Leroy Hood (BS '60, PhD '68).

Richards also embraced his role as an educator and acted as a mentor to generations of undergraduate and graduate students, as well as to faculty, during his nearly six decades at Caltech. "He really liked being with students and was stimulated by that interaction," Rees recalls. "He was able to teach up to the very end. I think that meant a lot to him."

"Jack was a co-advisor for my thesis work and an incredible mentor. He joyously encouraged and supported risk taking and strongly influenced my entry into the protein engineering field," says Stephen Mayo (PhD '88), Caltech's William K. Bowes Jr. Leadership Chair of the Division of Biology and Biological Engineering and Bren Professor of Biology and Chemistry. "Jack's advice and mentorship didn't stop after I completed my degree. He was a great sounding board for discussing research directions, and he provided incredibly clear career advice that was often delivered with humorous anecdotes that made our sometimes intense discussions easier. I owe Jack a great deal and will miss him as a mentor and colleague but, most importantly, as a friend."

"It's hard to imagine the sort of changes that you would see in this, in any place, over 58 years," Rees adds. "It's a long baseline. But he liked brainstorming about new ideas and technologies. He was a key part of the biochemistry subgroup. If we were grappling with some issue and trying to figure out what the most prudent course of action was, he would often look at it from his unique perspective, and we would say, you know, that's right. He could really unite us. He leaves a hole."

Richards is survived by his second wife, Minnie McMillan, professor of molecular microbiology and immunology and professor of neurology at the University of Southern California's Keck School of Medicine. Richards also leaves behind four daughters from his first marriage (to Marian King), Kathleen Fraga of Grass Valley, California; Jennifer Welton of Belgrade, Montana; Julia Hart of Clayton, California; and Cynthia Clapp of Corvallis, Oregon; and four grandchildren.

He will be buried in Nevada City, California, where his grandfather and favorite uncle lived.

Writer: 
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