Friday, February 13, 2015
Center for Student Services 360 (Workshop Space) – Center for Student Services

Backpocket Barnburner: A Lightning Quick Overview of Educational Theory

Why Do We Feel Thirst? An Interview with Yuki Oka

To fight dehydration on a hot summer day, you instinctively crave the relief provided by a tall glass of water. But how does your brain sense the need for water, generate the sensation of thirst, and then ultimately turn that signal into a behavioral trigger that leads you to drink water? That's what Yuki Oka, a new assistant professor of biology at Caltech, wants to find out.

Oka's research focuses on the study of how the brain and body work together to maintain a healthy ratio of salt to water as part of a delicate form of biological balance called homeostasis.

Recently, Oka came to Caltech from Columbia University. We spoke with him about his work, his interests outside of the lab, and why he's excited to be joining the faculty at Caltech.

 

Can you tell us a bit more about your research?

The goal of my research is to understand the mechanisms by which the brain and body cooperate to maintain our internal environment's stability, which is called homeostasis. I'm especially focusing on fluid homeostasis, the fundamental mechanism that regulates the balance of water and salt. When water or salt are depleted in the body, the brain generates a signal that causes either a thirst or a salt craving. And that craving then drives animals to either drink water or eat something salty.

I'd like to know how our brain generates such a specific motivation simply by sensing internal state, and then how that motivation—which is really just neural activity in the brain—goes on to control the behavior.

 

Why did you choose to study thirst?

After finishing my Ph.D. in Japan, I came to Columbia University where I worked on salt sensing mechanisms in the mammalian taste system. We found that the peripheral taste system has a key function for salt homeostasis in the body by regulating our salt intake behavior. But of course, the peripheral sensor does not work by itself.  It requires a controller, the brain, which uses information from the sensor. So I decided to move on to explore the function of the brain; the real driver of our behaviors.

I was fascinated by thirst because the behavior it generates is very robust and stereotyped across various species. If an animal feels thirst, the behavioral output is simply to drink water. On the other hand, if the brain triggers salt appetite, then the animal specifically looks for salt—nothing else. These direct causal relations make it an ideal system to study the link between the neural circuit and the behavior.

 

You recently published a paper on this work in the journal Nature. Could you tell us about those findings?

In the paper, we linked specific neural populations in the brain to water drinking behavior. Previous work from other labs suggested that thirst may stem from a part of the brain called the hypothalamus, so we wanted to identify which groups of neurons in the hypothalamus control thirst. Using a technique called optogenetics that can manipulate neural activities with light, we found two distinct populations of neurons that control thirst in two opposite directions. When we activated one of those two populations, it evoked an intense drinking behavior even in fully water-satiated animals. In contrast, activation of a second population drastically suppressed drinking, even in highly water-deprived thirsty animals.  In other words, we could artificially create or erase the desire for drinking water.

Our findings suggest that there is an innate brain circuit that can turn an animal's water-drinking behavior on and off, and that this circuit likely functions as a center for thirst control in the mammalian brain. This work was performed with support from Howard Hughes Medical Institute and National Institutes of Health [for Charles S. Zuker at Columbia University, Oka's former advisor].

 

You use a mouse model to study thirst, but does this work have applications for humans?

There are many fluid homeostasis-associated conditions; one example is dehydration. We cannot specifically say a direct application for humans since our studies are focused on basic research. But if the same mechanisms and circuits exist in mice and humans, our studies will provide important insights into human physiologies and conditions.

 

Where did you grow up—and what started your initial interest in science?

I grew up in Japan, close to Tokyo, but not really in the center of the city. It was a nice combination between the big city and nature. There was a big park close to my house and when I was a child, I went there every day and observed plants and animals. That's pretty much how I spent my childhood. My parents are not scientists—neither of them, actually. It was just my innate interest in nature that made me want to be a scientist.

 

What drew you to Caltech?

I'm really excited about the environment here and the great climate. That's actually not trivial; I think the climate really does affect the people. For example, if you compare Southern California to New York, it's just a totally different character. I came here for a visit last January, and although it was my first time at Caltech I kind of felt a bond. I hadn't even received an offer yet, but I just intuitively thought, "This is probably the place for me."

I'm also looking forward to talking to my colleagues here who use fMRI for human behavioral research. One great advantage about using human subjects in behavioral studies is that they can report back to you about how they feel. There are certainly advantages of using an animal model, like mice. But they cannot report back. We just observe their behavior and say, "They are drinking water, so they must be thirsty." But that is totally different than someone telling you, "I feel thirsty." I believe that combining advantages of animal and human studies should allow us to address important questions about brain functions.

 

Do you have any hobbies?

I play basketball in my spare time, but my major hobby is collecting fossils. I have some trilobites and, actually, I have a complete set of bones from a type of herbivorous dinosaur. It is being shipped from New York right now and I may put it in my new office.

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Why Do We Feel Thirst?
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Saturday, January 24, 2015
Center for Student Services 360 (Workshop Space) – Center for Student Services

The personal side of science

Wednesday, February 4, 2015
Center for Student Services 360 (Workshop Space) – Center for Student Services

Meet the Outreach Guys: James & Julius

Wednesday, February 18, 2015
Center for Student Services 360 (Workshop Space) – Center for Student Services

HALF TIME: A Mid-Quarter Meetup for TAs

Four Caltech Professors Elected to National Academy of Inventors

Caltech professors Frances Arnold, David Baltimore, Carver Mead, and Axel Scherer have been named fellows of the National Academy of Inventors (NAI).

Election as an NAI fellow is an honor bestowed upon academic innovators and inventors who have "demonstrated a prolific spirit of innovation in creating or facilitating outstanding inventions and innovations that have made a tangible impact on quality of life, economic development, and the welfare of society." Fellows are named inventors on U.S. patents and were each nominated by their peers for their contributions to innovation.

According to its website, the NAI "was founded in 2010 to recognize and encourage inventors with patents issued from the U.S. Patent and Trademark Office, enhance the visibility of academic technology and innovation, encourage the disclosure of intellectual property, educate and mentor innovative students, and translate the inventions of its members to benefit society."

Frances Arnold is the Dick and Barbara Dickinson Professor of Chemical Engineering, Bioengineering and Biochemistry, and director of the Donna and Benjamin M. Rosen Bioengineering Center at Caltech. Her group has pioneered methods of "directed evolution" to engineer new proteins in the lab. The method is now widely used to create catalysts for use in industrial processes, including the production of fuels and chemicals from renewable resources. The Arnold group also uses the results of laboratory evolution experiments to elucidate principles of biological design. Arnold is a coinventor on more than 40 U.S. patents. She was inducted into the National Inventors Hall of Fame in 2014 and received the National Medal of Technology and Innovation in 2013.

David Baltimore is the Robert Andrews Millikan Professor of Biology, and President Emeritus of Caltech. His research group focuses on two major areas: investigation of the development and functioning of the mammalian immune system, and translational studies of the viral transfer of genes into immune cells to increase their ability to fight disease and resist cancer. He was awarded the Nobel Prize in Physiology or Medicine in 1975.

Carver Mead (BS '56, MS '57, PhD '60) is the Gordon and Betty Moore Professor of Engineering and Applied Science, Emeritus, in computation and neural systems. Mead has significantly advanced the technology of integrated circuits by developing a method called very-large-scale integration (VSLI) that allows engineers to combine thousands of transistors onto a single microchip, thus exponentially expanding computer processing power. He received the National Medal of Technology and Innovation in 2002.

Axel Scherer is the Bernard Neches Professor of Electrical Engineering, Medical Engineering, Applied Physics and Physics, and the director of the Caltech Global Health Initiative. Holding more than 100 patents in the area of nanofabrication and device design, Scherer has most recently developed ways to integrate optics, electronics, and fluidics into sensor systems. Much of his work is currently focused on systems for medical diagnosis and health monitoring through molecular pathology and wireless implants. Over the past decades, technology from his group has been commercialized through several start-up ventures in telecommunications and health care devices.

Arnold, Baltimore, Mead, and Scherer will join Vice Provost Morteza Gharib, the Hans W. Liepmann Professor of Aeronautics and Bioinspired Engineering, and Robert H. Grubbs, the Victor and Elizabeth Atkins Professor of Chemistry, as Caltech's Fellows of the NAI. They will be inducted during the fourth annual conference of the National Academy of Inventors, which will be held at Caltech on March 20, 2015.

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SKIES App Aids Learning in Caltech Classrooms

When you first walk into Bruce Hay's genetics class, it looks like any other 21st-century college lecture hall: the professor, backed by his PowerPoint slides, faces a room full of students with iPads. However, as Hay delivers a lecture about the mechanisms that inhibit gene expression, a rectangular yellow bubble suddenly pops up on the screen below his lecture slide. It's from a student, asking a question about RNA interference. Soon another bubble pops up, this one with a link to a video that explains how microRNAs can affect the color pattern of flower petals. Other bubbles branch off from each other, and hands rise into the air.

Suddenly, you realize you're in the classroom of the future.

Those pop-up bubbles are a key component of a new interactive lecture format made possible by an app developed by two Caltech alums and brought to campus by Caltech's Center for Teaching, Learning, and Outreach (CTLO). The iPad app—produced by Su-Kam Intelligent Education Systems, or SKIES, named after cofounders Julius Su (BS '98, BS '99, PhD '07) and Victor Kam (PhD '08)—is now being used in several classes on campus.

"It's been known for a long time that lecturing—just a professor teaching and the students passively listening—is not an optimal way for students to learn. You always want to have students doing some thinking, some processing, and some recall during the lecture," says Su, who is a CTLO program manager in addition to being one of the cofounders of SKIES.

With this in mind, Su and his colleagues at CTLO have been experimenting with ways to change the traditional Caltech classroom. The SKIES app is based on one such approach—active learning, which gets students participating in a variety of ways, and is supported by a great deal of evidence indicating its effectiveness.

The wiki-like app facilitates this kind of active learning by allowing students to directly interact with lecture materials both inside and outside the classroom. The app compiles and connects notes, links, videos, and other materials—contributed by students, teaching assistants, and the professor—into a branching tree of collective knowledge stemming from an initial seed of slides or other multimedia material.

This concept of students and teachers interacting to create knowledge together is what drew Professor of Biology Bruce Hay to become one of the first users of the SKIES app in 2012.


Students can ask questions during Hay's lecture in the SKIES app. The questions or comments pop up below the lecture slide in real time.

"The big struggle that I have—and that lots of people have—is just getting students to ask questions; getting people to turn the class into more of a discussion rather than just the lecturer speaking," Hay says. "I knew that Julius and Victor were developing this prototype, and I thought, I've been teaching this same course for 15 years now and maybe this would be a good idea, to just try something new that might make it a little more interactive."

In the three years Hay has used the app in his genetics class, he says the app has done just what he'd hoped it would: provided an alternative channel by which students can participate. During class, Hay says students often add cards to his lecture slides as a form of public note-taking; for example, in one lecture, a student added a card to a particular slide, saying, "Professor Hay says this would be an excellent exam question." After class is over, he says, students often post cards with questions about the day's materials; these can then be addressed by Hay or the class's teaching assistants, either directly in class or through another branch of cards in the app.

Hay says that the app lets him monitor what students are contributing—and it allows him to promote and highlight information he considers particularly helpful and relevant to understanding the lecture material. Conversely, the app also allows students to rate how well they understand his lecture slides, as well as the cards added by TAs and other students.

"After class, I take a look at the reviews to see how well the students understood what we talked about in class that day," Hay says. "If I see that a slide is rated green [the app's version of a thumb's up], I can assume that it was pretty straightforward and understandable. But if the students have rated it red, I can add extra material to the slide, like additional text or figures. Then, in the next class, I can go back and say, 'It looks like this part was a little bit difficult. Let's just go back and review it again before we go on to the new stuff.'"

Although these continuous double checks require a bit more effort on the part of the professor and the students, they seem to be paying off: Hay says the average grades in his class went up by almost a full grade point after his first year using the app. The improvement was so noticeable, he says, "it was actually almost frightening. That was probably the biggest indication this was making a difference in terms of learning, instead of just making it fun for me and them."


In the SKIES app, students create dialogue by adding 'cards' that branch off of the professor's lecture slides.

Hay says the added content from students in the SKIES app over the past three years has enabled his course "tree" to grow and improve each term. "I'm not just repeating all the same slides every year. Many of the slides stay the same, but now I add new things, based on what the students found helpful in terms of explanations, quiz questions, and examples. So everyone is involved in making the course better," he notes.

After hearing about some of the app's early successes, other instructors across campus began using SKIES in their courses. This includes Bill Goddard, Charles and Mary Ferkel Professor of Chemistry, Materials Science, and Applied Physics, who has used SKIES to teach lectures and manage group projects in his computational and theoretical chemistry classes; Jeff Mendez, lecturer in chemistry, who has used SKIES to teach the lecture portion of his freshman solar chemistry lab; and Yaser Abu-Mostafa, professor of electrical engineering and computer science, who has used SKIES to promote and manage discussions in the in-class portion of his well-regarded Learning From Data MOOC, which has attracted over 200,000 students within and outside Caltech since its inception.

The app is also being used by many Caltech outreach programs, such as the Summer Research Connection, the Community Science Academy, and Harry Gray's Solar Army, to broaden the impact of university initiatives at the K–12 level; and is being used to teach several classes at Pasadena City College, as well as in several local middle schools and high schools.

SKIES is currently only available on iPad and iPhone, and as the app's popularity has grown, support from the Provost's Innovation in Education Fund and the Bechtel Foundation fund has allowed CTLO to expand the use of SKIES on campus through the purchase of more iPads. In the future, Su hopes that the app's reach will grow even further, both on iPads and eventually by expanding the app to work on other operating systems.

Aside from those few comments on the hardware limitations, Su says the feedback he and his colleagues at the CTLO have received from professors and students who have been using SKIES has been overwhelmingly positive.

"CTLO is continually providing Caltech faculty and TAs with evidence about what helps students learn more effectively. Active and collaborative approaches tend to work well," he says. "This app is just one way to foster more active and collaborative learning, but I think we can already see that it's providing new ways for professors to make classes even more lively and engaging for students at Caltech."

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Tuesday, December 2, 2014
Guggenheim 101 (Lees-Kubota Lecture Hall) – Guggenheim Aeronautical Laboratory

PUSD: Annual Open Enrollment

New Center Supports Data-Driven Research

With the advanced capabilities of today's computer technologies, researchers can now collect vast amounts of information with unprecedented speed. However, gathering information is only one half of a scientific discovery, as the data also need to be analyzed and interpreted. A new center on campus aims to hasten such data-driven discoveries by making expertise and advanced computational tools available to Caltech researchers in many disciplines within the sciences and the humanities.

The new Center for Data-Driven Discovery (CD3), which became operational this fall, is a hub for researchers to apply advanced data exploration and analysis tools to their work in fields such as biology, environmental science, physics, astronomy, chemistry, engineering, and the humanities.

The Caltech center will also complement the resources available at JPL's Center for Data Science and Technology, says director of CD3 and professor of astronomy George Djorgovski.

"Bringing together the research, technical expertise, and respective disciplines of the two centers to form this joint initiative creates a wonderful synergy that will allow us opportunities to explore and innovate new capabilities in data-driven science for many of our sponsors," adds Daniel Crichton, director of the Center for Data Science and Technology at JPL.

At the core of the Caltech center are staff members who specialize in both computational methodology and various domains of science, such as biology, chemistry, and physics. Faculty-led research groups from each of Caltech's six divisions and JPL will be able to collaborate with center staff to find new ways to get the most from their research data. Resources at CD3 will range from data storage and cataloguing that meet the highest "housekeeping" standards, to custom data-analysis methods that combine statistics with machine learning—the development of algorithms that can "learn" from data. The staff will also help develop new research projects that could benefit from large amounts of existing data.

"The volume, quality, and complexity of data are growing such that the tools that we used to use—on our desktops or even on serious computing machines—10 years ago are no longer adequate. These are not problems that can be solved by just buying a bigger computer or better software; we need to actually invent new methods that allow us to make discoveries from these data sets," says Djorgovski.

Rather than turning to off-the-shelf data-analysis methods, Caltech researchers can now collaborate with CD3 staff to develop new customized computational methods and tools that are specialized for their unique goals. For example, astronomers like Djorgovski can use data-driven computing in the development of new ways to quickly scan large digital sky surveys for rare or interesting targets, such as distant quasars or new kinds of supernova explosions—targets that can be examined more closely with telescopes, such as those at the W. M. Keck Observatory, he says.

Mary Kennedy, the Allen and Lenabelle Davis Professor of Biology and a coleader of CD3, says that the center will serve as a bridge between the laboratory-science and computer-science communities at Caltech. In addition to matching up Caltech faculty members with the expertise they will need to analyze their data, the center will also minimize the gap between those communities by providing educational opportunities for undergraduate and graduate students.

"Scientific development has moved so quickly that the education of most experimental scientists has not included the techniques one needs to synthesize or mine large data sets efficiently," Kennedy says. "Another way to say this is that 'domain' sciences—biology, engineering, astronomy, geology, chemistry, sociology, etc.—have developed in isolation from theoretical computer science and mathematics aimed at analysis of high-dimensional data. The goal of the new center is to provide a link between the two."

Work in Kennedy's laboratory focuses on understanding what takes place at the molecular level in the brain when neuronal synapses are altered to store information during learning. She says that methods and tools developed at the new center will assist her group in creating computer simulations that can help them understand how synapses are regulated by enzymes during learning.

"The ability to simulate molecular mechanisms in detail and then test predictions of the simulations with experiments will revolutionize our understanding of highly interconnected control mechanisms in cells," she says. "To some, this seems like science fiction, but it won't stay fictional for long. Caltech needs to lead in these endeavors."

Assistant Professor of Biology Mitchell Guttman says that the center will also be an asset to groups like his that are trying to make sense out of big sets of genomic data. "Biology is becoming a big-data science—genome sequences are available at an unprecedented pace. Whereas it took more than $1 billion to sequence the first genome, it now costs less than $1,000," he says. "Making sense of all this data is a challenge, but it is the future of biomedical research."

In his own work, Guttman studies the genetic code of lncRNAs, a new class of gene that he discovered, largely through computational methods like those available at the new center. "I am excited about the new CD3 center because it represents an opportunity to leverage the best ideas and approaches across disciplines to solve a major challenge in our own research," he says.

But the most valuable findings from the center could be those that stem not from a single project, but from the multidisciplinary collaborations that CD3 will enable, Djorgovski says. "To me, the most interesting outcome is to have successful methodology transfers between different fields—for example, to see if a solution developed in astronomy can be used in biology," he says.

In fact, one such crossover method has already been identified, says Matthew Graham, a computational scientist at the center. "One of the challenges in data-rich science is dealing with very heterogeneous data—data of different types from different instruments," says Graham. "Using the experience and the methods we developed in astronomy for the Virtual Observatory, I worked with biologists to develop a smart data-management system for a collection of expression and gene-integration data for genetic lines in zebrafish. We are now starting a project along similar methodology transfer lines with Professor Barbara Wold's group on RNA genomics."

And, through the discovery of more tools and methods like these, "the center could really develop new projects that bridge the boundaries between different traditional fields through new collaborations," Djorgovski says.

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Wednesday, October 29, 2014
Center for Student Services 360 (Workshop Space) – Center for Student Services

Meet the Outreach Guys: James & Julius

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