Special Delivery

From the exploration of other planets to the meanderings of single cells through our bloodstream and into our tissues, Caltech and JPL researchers are thinking about transportation in unexpected ways. They're using transformative delivery methods to land on Mars, collect data in hard-to-reach locales, and shepherd drugs to the brain.

For example, chemical engineer Mark Davis is building on his experience with nanomaterials to create a nanoparticle delivery vehicle that would encapsulate chemotherapeutics and carry them to where they are supposed to go in the body. These nanoparticles should stay in the blood until they reach a tumor and then release their payload, thus allowing the drugs to destroy solid tumors while sparing healthy tissue.

Lance Christensen, a senior atmospheric scientist at JPL, invents tunable laser spectrometers that basically sniff the atmosphere for trace measurements of gases. Such spectrometers can be carried on drones to measure the abundance of atmospheric gases such as methane, water vapor, and carbon dioxide.

And then there's geochemist Ken Farley, the project scientist for Mars 2020, the new rover mission. He is helping define the science goals for the Mars 2020 mission and determining how to pack an assembly of all-new scientific instruments onto an existing rover. And he has to do all this in time to meet the "very hard" launch date of 2020—when Mars and Earth are closest in orbit to each other.

The overall focus for all of these researchers is to better be able to ask big questions about the origins of life, to monitor the earth's emissions and overall health, and even to treat some of the most devastating diseases we encounter. For more about their efforts, read Special Delivery on E&S+.

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Jack Roberts's Online Success

At 98 years of age, John D. "Jack" Roberts, Caltech Institute professor of chemistry, emeritus, recently became a best-selling online author.

On June 8, Roberts turned 98; just a few days later, his textbook, Basic Principles of Organic Chemistry, surpassed 500,000 file downloads. He wrote the first edition with his protégé Marjorie C. Caserio in 1964. The second edition, created in 1977, is now available online for free at the Caltech Library, where it has been doing brisk business: since December 2012, when accurate records of the book's popularity began being maintained, more than 502,000 copies have been downloaded.

Roberts, a proponent of open access to scholarly material, has worked with the Caltech Library for the last decade to make five of his previously published textbooks freely available.

"Since being included in CaltechAUTHORS in September 2011, Basic Principles of Organic Chemistry has accounted for more than 10 percent of all file downloads," says George Porter, Caltech's engineering librarian. "This is more than twice the download activity of CaltechAUTHORS' second most highly used resource."

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2016 Distinguished Alumna: Ellen D. Williams (PhD ’82, Chemistry)

The 2016 Distinguished Alumni Awards were presented on Saturday, May 21, during the 79th annual Seminar Day. Each week, the Caltech Alumni Association will share a story about a recipient.

In early March of this year, Ellen Williams stood before an audience of more than 2,000 researchers, entrepreneurs, and policymakers gathered in Washington, D.C., to discuss the future of energy. 

"We are living in a time as dynamic as when Thomas Edison and his contemporaries experimented with electricity," she declared as master of ceremonies for the Energy Innovation Summit, a conference that included as speakers luminaries such as former Vice President Al Gore and U.S. Secretary of Energy Ernest Moniz. "Drawing upon the science and engineering developments of recent decades, and supported by stunning advances in computational capability, today's innovators are pushing the boundaries of what is possible with energy."

Williams should know. As the director for the Advanced Research Project Agency–Energy (ARPA-E), which hosted the summit, she heads an organization that has invested more than $1.3 billion in hundreds of energy-related projects. Her position at the forefront of energy research is the culmination of a long career at the intersection of cutting-edge science, industry, and public policy.

Read the full story on the Caltech Alumni Association website

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Williams received the award for her sustained record of innovation and achievement in the area of structural-surface physics.
Wednesday, August 24, 2016
Center for Student Services 360 (Workshop Space) – Center for Student Services

CTLO's Summer Short Course for Faculty: (Re)Designing Your Class

Wednesday, September 21, 2016

SAVE THE DATE - 4th Annual Caltech Teaching Conference -- Details Coming Soon!

Wednesday, July 13, 2016
Noyes 147 (J. Holmes Sturdivant Lecture Hall) – Arthur Amos Noyes Laboratory of Chemical Physics

Teaching Statement Workshop

Gupta Receives Library Friends' Thesis Prize

Senior Ayush Gupta has been named as the winner of this year's Library Friends' Senior Thesis Prize. The Thesis Prize, established in 2010, is intended to encourage undergraduates to complete a formal work of scholarship as a capstone project for their undergraduate career and to recognize sophisticated in-depth use of library and archival research. For their achievement, recipients of the $1,200 prize are listed in the commencement program. This year's prizes were announced and awarded at a reception at Alumni House on Tuesday, June 1, with students, alumni, Friends of the Caltech Libraries, library staff, and faculty present.

Gupta's thesis was titled "Noncovalent Immobilization of Electrocatalysts on Carbon Electrodes via a Pyrenyl Ligand" and he completed the work under the supervision of his advisor, Harry Gray, the Arnold O. Beckman Professor of Chemistry and Founding Director of the Beckman Institute. Gray remarked that Gupta "has developed into an independent investigator, cleverly and adeptly using library resources."

"I began my research in Harry Gray's group during the spring of 2013 and I quickly became interested in looking into catalysis for the production of solar fuels," Gupta says. "My first project expanded into what I have been working on for the past three years, focusing on attaching molecular catalysts to graphitic electrodes. Attaching catalysts to electrode surfaces is one route to easily assemble devices that can convert renewable energy, like solar, into chemical fuels."

"Writing a thesis that encompasses all of my research at Caltech was a daunting task," he says. "Luckily, I was able to combine many of the smaller reports I had completed as a part of the SURF program and then further elaborate on those topics in my thesis. Another challenge was finding ways to blend in all the various parts of my research into a cohesive narrative, but I was able to get a lot of help both from my advisor Harry Gray and my supervisor James Blakemore."

Gupta will be attending the University of Chicago in the fall to begin work on a PhD in chemistry.

Caltech faculty nominate seniors whose theses they deem to be deserving of the prize. Nominated students then supply a research narrative that explains their research methodology, detailing not only the sources they used but the way they obtained access to them.

Other finalists for the prize were Kurtis Carsch, nominated by Professor Theodor Agapie for his thesis in chemistry; Harinee Maiyuran, nominated by Professor Steven Quartz for her thesis in history and philosophy of science; and Monica Li, nominated by Professor Beverly McKeon for her thesis in aerospace.

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Gupta Receives Library Friends' Thesis Prize
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The winner of this year's Library Friends' Senior Thesis Prize was announced on June 1.

Newly Named Pew Scholar to Image Gut Bacteria with Sound Waves

Caltech's Mikhail Shapiro, assistant professor of chemical engineering, has been selected as a 2016 Pew scholar by the Pew Scholars Program in the Biomedical Sciences. As a Pew Scholar, Shapiro will receive $240,000 over the next four years in support of his research program to image the location and activities of microbes in the body using ultrasound.

Our guts, or intestines, are alive with colonies of bacteria. Some species are good for us but others are bad and can lead to medical conditions, such as food poisoning and irritable bowel disease. Observing these bacteria in action is difficult because they are hidden deep inside the body. Typically, researchers culture the microbes outside the body to learn more about them, but this does not reveal where the bacteria are in the gut, or how they interact.

Shapiro plans to solve this problem with bacteria genetically engineered to be visible to ultrasound. The same ultrasound imaging techniques used by doctors to take pictures of a developing baby could be used to visualize communities of bacteria in the gut.

"Imaging techniques that rely on photons, such as fluorescence or luminescence, don't penetrate very deeply into the body," says Shapiro. "We are developing proteins that cells can make that will allow them to interact with sound waves and magnetic fields, which can penetrate more deeply."

The key to the approach is a unique class of proteins normally employed by certain photosynthetic, single-celled organisms to control how much they float, a trait needed to regulate access to light and other nutrients. The proteins form gas-filled structures that, Shapiro's team discovered, can scatter sound waves in a manner that makes them detectable by ultrasound. The researchers plan to genetically engineer bacteria to produce the proteins, then image them in mice.

The technique could ultimately lead to better ways to diagnose conditions such as irritable bowel disease.

Shapiro came to Caltech from UC Berkeley in 2014. Before that, he was a postdoctoral fellow at the University of Chicago, and earned his PhD from the Massachusetts Institute of Technology.

The Pew Scholars Program in the Biomedical Sciences, according to their website, "provides funding to young investigators of outstanding promise in science relevant to the advancement of human health. The program makes grants to selected academic institutions to support the independent research of outstanding individuals who are in their first few years of their appointment at the assistant professor level."

In addition to engineering bacteria, Shapiro's lab works on other methods to image and control cells deep in our body—such as tumor cells, immune cells, and neurons—with ultrasound and magnetic resonance.

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The Next Big Thing

To get a glimpse into the future, what better place is there to look than the minds of those about to become Caltech's newest alumni? After all, our 2016 graduates have been at the forefront of research in vastly different fields for the past few years. Their unique perspectives have informed their ideas of the future, and their work will reach far beyond the confines of a lab.

With that in mind, in the Summer 2016 issue of E&S magazine, we talked to a handful of undergraduate and graduate students prior to commencement to find out what they think will be the next big thing in science and engineering and how their plans after graduation reflect those ideas.

 

I believe that the future of science, technology, engineering, and mathematics (STEM) will place a greater emphasis on implementation and impact of research. While rapid economic growth and globalization have introduced numerous difficult challenges, society has acquired powerful new tools and technology to develop and implement solutions for these issues.

I will be working as a management consultant after graduating to expose myself to business and strategy. That way, I can perhaps one day help new discoveries and ideas produce a tangible impact on people's lives."

Aditya Bhagavathi
BS in Computer Science

 

I believe the future of planetary and space exploration will follow two paths—one, the search for life beyond Earth within the solar system, and two, the characterization of exoplanets.

For the solar system, the initial survey of its major worlds was just completed with the New Horizons flyby of Pluto, and therefore a new focus will likely emerge. That initial survey has revealed several worlds to be potentially habitable, including Mars, Europa, and Enceladus, with the former two already targets for future missions. These new missions will not only reveal more about these worlds but also force us to reevaluate what life is, how it arises, and how it endures.

For exoplanets, the diversity of worlds is immense. From giant planets that orbit their host stars in less than a day to habitable planets with permanent daysides and nightsides, exoplanets offer a tremendous opportunity to understand the planets in our own solar system. With the rapid development of technologies, instruments, and observing techniques, the flood of data regarding exoplanets will only continue. I plan to be among the scientists who will analyze this data and combine their results with theoretical models to investigate what these distant worlds are like. By doing this, we will be exploring our place in the universe and whether we are alone within it."

Peter Gao
PhD in Planetary Science

 

When asked what he would do with his degree in philosophy during a routine dentist appointment, David Silbersweig, MD at Brigham and Women's Hospital and Academic Dean at Harvard Medical School, responded with a single word that spoke volumes: 'Think.' Simply put, I too want to think.

I want to learn how to think at a complex level such that my ability to think and subsequently solve problems allows me to change lives. The history and philosophy of science degree at Caltech has given me exactly this. According to Silbersweig, 'If you can get through a one-sentence paragraph of Kant, holding all of its ideas and clauses in juxtaposition in your mind, you can think through most anything.' In my first History and Philosophy of Science class, I read Kant. I also find immense happiness in working with and helping other individuals, a sense of euphoria matched by little else in life. I learned this lesson through tutoring students and coaching younger athletes. And finally, as a collegiate athlete myself, I have undergone multiple orthopedic surgeries that ignited an interest in the musculoskeletal system and its ability to suffer injury yet recover remarkably. Together, these three aspects of life are central to my vision of the future. Becoming an orthopedic surgeon is the perfect combination—the career that will give me these components and a lot more.

One of the major developments in medicine will be 3-D printing, primarily in order to provide individuals with replacement bones and organs. Combining new progress in computer science will facilitate immense progress in 3-D printing, which also aligns well with the use of robotics in surgery. As an athlete who has torn my ACL and had bone spurs in the past year, I'm excited to be a part of this field in the future and hopefully help other athletes succeed in pursuing their passions."

Harinee Maiyuran
BS in History and Philosophy of Science

 

My personal hunch, and perhaps a somewhat common one, is that all disciplines—and not just STEM ones—are moving toward being increasingly data driven, a phenomenon rooted in freer dissemination and greater influx of research data. Correspondingly, computers and programming drive data processing in all disciplines; a common joke is that every scientist is automatically a software engineer. Statistical and machine learning techniques that are designed to tackle vast quantities of data are increasingly common in academic papers and will probably continue to climb in popularity.

I am planning to go into computational astrophysics research because I believe that the recent influx of data from new detectors will drive a huge surge of research questions to be investigated. And as a physics/computerscience double major, I'm uniquely equipped to analyze big data and extract scientific meaning from it."

Yubo Su
BS in Physics and Computer Science

 

Many aspects about future climate are unclear, such as how cloudiness, precipitation, and extreme events will change under global warming. But recent progress in observational and computational technology has provided great potential for clarifying these uncertainties. I plan to continue my research and utilize new data and models to develop theoretical understanding of these problems. I hope that such new insight will be helpful for assessing climate change impacts and designing effective adaptation and mitigation strategies."

Zhihong Tan
PhD in Environmental Science and Engineering

 

The future of science and engineering depends on closing the huge gap between the general public and scientists and engineers. I think this stems from a good deal of ignorance about what it is we do and hope to achieve, which leads to misconceptions about our work and community, and the separation between 'us' and 'them.' But if we're trying to understand and solve problems that affect everyone, shouldn't everyone be more involved?

When I graduate, I'm going to take a year off to try and bridge this gap in my own life. I don't know what I'll do yet, but it will be decidedly nonacademic. I want to travel, work odd jobs, and pursue hobbies I've set aside to finish my education. If I want to help people understand why I do what I do, I need to be certain that I understand first. After only four years surrounded almost exclusively by scientists and engineers, I want to get away a little. That way, when I inevitably return, I'll have a bit more perspective."

Valerie Pietrasz
BS in Mechanical Engineering and Planetary Science

 

Driven by the goal of reducing fossil fuel use and pollution, clean energy research plays and will play a pivotal role in America's energy future. Clean energy research spans disciplines such as biological and environmental sciences, advanced materials, nuclear sciences, and chemistry. Therefore, multidisciplinary efforts are not only necessary but also crucial to develop and deploy real-world solutions for energy security and protecting the environment.

As a graduate student, I have focused on understanding nanoscale energy transport in novel energy-efficient materials. In the future, I plan to further advance and apply my expertise to solve real-world problems in an integrated and multidisciplinary approach. I hope this effort will eventually lead to developing advanced clean energy technologies that could not only ease today's energy crisis but also improve our quality of life."

Chengyun Hua
PhD in Mechanical Engineering

 

I believe that in the next decade, the behavioral and computational subfields of neuroscience will work together seamlessly. I think this change will be primarily fueled by the development of new tools that allow us to measure the activity of large populations of neurons more precisely.

A prominent behavioral method of research, in mice at least, is to activate large structures in the brain and observe the aggregate behavioral effect. However, it is unlikely that all of these neurons are responsible for the same signal, so this approach may be too crude. I think new measurement techniques will enable behavioralists to collect large-scale population activity that computationalists can use in order to find subtle differences of function within these structures. Hopefully this collaboration will lead to generating and validating fundamental theories underlying how the brain works.

Currently, I am in the process of developing a method to measure the activity from over 10,000 neurons simultaneously. I hope to validate this technique before I graduate and then apply it to studying large-scale population activity during various behaviors. My future aim is to work closely with computationalists with the hope of discovering fundamental theories of brain function."

Gregory Stevens
BS in Biology

 

I think the future of planetary science is to discover and characterize more and more extra-solar planets, including their orbital configurations, atmospheres, and habitability. This is a challenging task because it requires a solid understanding of how chemistry and physics work on a planetary scale. Learning more about the planets closest to us paves a way toward the understanding of exoplanets that are far beyond our reach, since we can send missions to them. So after graduation, I will join the team for Juno—the spacecraft that will arrive at Jupiter in summer 2016—at JPL. New discoveries about Jupiter will also tell us more about what other planets beyond our solar system could look like."

Cheng Li
PhD in Planetary Science

 

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The Next Big Thing
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We hear from a handful of graduating students to learn what they think will be the next big thing in science and engineering and how their plans reflect those ideas.

Solving Molecular Structures

Determining the chemical formula of a protein is fairly straightforward, because all proteins are essentially long chains of molecules called amino acids. Each chain, however, folds into a unique three-dimensional shape that helps produce the characteristic properties and function of the protein. These shapes are more difficult to determine (or "solve"); scientists traditionally do so using a technique called X-ray crystallography, in which X-rays are shot through a crystallized sample and scatter off the atoms in a distinctive pattern.

This spring, Caltech students had the opportunity to use the technique to solve protein structures themselves in a new course taught by Professor of Chemistry André Hoelz.

Although the Institute has a long history in the fields of structural biology and X-ray crystallography, the chance to get hands-on experience with the technique is rare at most universities, Caltech included. Indeed, the method is more commonly performed at specialized facilities with high-energy X-ray beam lines, including the Stanford Synchrotron Radiation Laboratory (SSRL). However, in 2007, thanks to a gift from the Gordon and Betty Moore Foundation, Caltech opened the Molecular Observatory—a dedicated, completely automated radiation beam line at SSRL.

"The Molecular Observatory gives us lots of beam time," notes Hoelz. "Recently, I also received a grant from the Innovation in Education Fund from the Provost's Office that was matched by the Division of Chemistry and Chemical Engineering, and this allowed me the opportunity to develop this course and train students in a way not commonly found at universities."

In the new course, "Macromolecular Structure Determination with Modern X-ray Crystallography Methods" (BMB/Ch 230), Hoelz's students have been using the Molecular Observatory and other on-campus crystallization resources to solve the structures of various proteins, in particular, variants of green fluorescent proteins (GFPs)—proteins that exhibit bright green fluorescence under certain wavelengths of light. "These proteins are crucial tools in biology because they can be visualized by fluorescence techniques. It's important to know their physical structure, because it affects the intensity and wavelength at which the protein fluoresces," says Anders Knight, a first-year graduate student studying protein engineering with Frances Arnold, the Dick and Barbara Dickinson Professor of Chemical Engineering, Bioengineering and Biochemistry, and one of nine students—including two undergraduates—in the inaugural class.

During the first few weeks of the course, students determined the proper conditions—the pH levels and the mix of salts and buffer solutions—that are required to get a protein to crystallize. These conditions vary from protein to protein, making it tricky to "grow" perfect single crystals of the proteins. "Most of the ones we are working with have known 3-D structures, and they crystallize relatively easily, so they are a great place to start learning about the technique of X-ray crystallography," Knight says. "But some of us were also given protein variants that had never been crystallized before."

Once the students crystallized their proteins, single crystals were mounted in tiny nylon loops that are attached to small metal bases, frozen in liquid nitrogen, and loaded into pucks that were shipped to SSRL. There, the pucks were loaded into a robotic machine—remotely controllable from Caltech and operated by the students—that placed them, one by one, into a powerful X-ray beam. X-rays are scattered at characteristic angles by the electrons within the crystallized samples, generating a diffraction pattern that can be converted into a so-called electron-density map, which is then used to determine the 3-D location of all of the atoms.

"The electron density map doesn't exactly show you what the protein's structure is," Knight says. "You do have to correctly interpret the electron density map to determine where the protein's atoms will go. It's difficult, but this class is designed to give us practice doing that. Collecting data at SSRL was a great learning experience. It was interesting to be able to accurately mount and position the crystals—each smaller than a millimeter—on the beamline from hundreds of miles away. The data collection went fairly quickly, taking around eight minutes."

For their final assignment, students will write a mock journal paper about their methods and the final protein structure. Most of the structures had been determined previously, but one student did solve a previously unknown GFP structure, a bright red fluorescent protein called dTomato.

"dTomato is a product of directed evolution in protein engineering, created by subjecting its parent, DsRed, through several rounds of random genetic mutations," says Phong Nguyen, a graduate student in the lab of Doug Rees, Roscoe Gilkey Dickinson Professor of Chemistry and Howard Hughes Medical Institute Investigator, and the student who solved the structure of dTomato in Hoelz's class. "By solving its structure, we can see how directed evolution—a method developed by Frances Arnold to create new proteins using the principles of evolution—changed the protein from its parent. Specifically, we are able to explain how individual mutations contributed to the structural outcome of the protein and consequently to differing chemical and physical properties from the parent. We all are so excited to solve a new structure and contribute knowledge to the field of GFP protein engineering."

"Having the Molecular Observatory at Caltech allows us to train students with very sophisticated technology," says Hoelz, who is now envisioning a second, related course. "Students would learn recombinant protein expression and purification, directly prior to this course, so they can purify the proteins themselves with cutting-edge technology and then go on to determine their 3D structure by X-ray crystallography," he says.

"In my opinion, learning by doing is the best way to master how to determine crystal structures and this new course will solidify the strong roots Caltech has in X-ray crystallography," Hoelz adds. "Not only will this new course accelerate the otherwise slow learning process for this technique, but it will also allow non-structural biology laboratories on campus to determine crystal structures of their favorite proteins using Molecular Observatory, a unique and spectacular facility at Caltech."

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Solving Molecular Structures
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At Caltech, students have the opportunity to learn X‑ray crystallography, a technique that reveals the three-dimensional structure of molecules like proteins.

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