UF Explore Magazine | Summer 2014

SUMMER 2014

Big Data Research Opportunities Grow Exponentially

Dr. Bernie Machen President

Summer 2014, Vol. 19, No. 2

Dr. David Norton Vice President for Research Board of Trustees C. David Brown II, Orlando – Chair Susan Cameron, Ft. Lauderdale Christopher T. Corr, Lake Lure NC Charles B. Edwards, Ft. Myers James W. Heavener, Winter Park Marc Heft, Gainesville Carolyn K. Roberts, Ocala Jason J. Rosenberg, Gainesville Juliet Murphy Roulhac, Plantation Steven M. Scott, Boca Raton David M. Thomas, Windermere Cory Yeffet, Gainesville Explore is published by the UF Office of Research. Opinions expressed do not reflect the official views of the university. Use of trade names implies no endorsement by the University of Florida. Š 2014 University of Florida. explore.research.ufl.edu Editor: Joseph M. Kays joekays@ufl.edu Art Director: Katherine Kinsley-Momberger Design and Illustration: Katherine Kinsley-Momberger Paul Messal Nancy Schreck Writers: Cindy Spence Claire Baralt Copy Editor: Andrew Kays Printing: StorterChilds Printing, Gainesville Member of the University Research Magazine Association www.urma.org

About the cover: Out of the Darkness iDigBio is revealing new research opportunities in long-hidden museum collections.

This 3-D graphical rendering of a petascale computer shows the complexity of current state-ofthe-art computing systems and the challenge of developing the computer of the future, which would operate at exascale, performing a quintillion operations per second.

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Extracts Cover Story

24

5

Research News Briefs

Vision Quest Harnessing the power of predictive science.

12

Trail Blazers

UF Rising

Metabolites map biological processes in all living things.

Human-centered computing takes off.

30

David Norton Vice President for Research

The capacity to collect, store and analyze vast troves of information will be essential to scientific inquiry and, in fact, represents a revolution.

Instead of asking a question and gathering data, scientists can now look for patterns in data that will help them ask better, bigger questions.

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Summer 2014

S

ome 90 percent of all data that exists today was created in the last two years, but only half a percent has been analyzed.

Big Data represents a big opportunity for science, and the University of Florida is poised to take advantage of it.

UF already has momentum in the area. Last year the university unveiled Florida’s fastest supercomputer, known as HiPerGator. It also expanded its data pipeline to allow researchers to share enormous amounts of information at high speed, establishing a level of connectivity with few rivals on university campuses anywhere in the nation. In addition to the investment in infrastructure, UF is recruiting as many as 25 new faculty experts through the UF Rising campaign.

And UF is leveraging the talent already here. In the decade-long iDigBio project, UF researchers are coordinating a nationwide effort to digitize up to 1 billion specimens in the collections of dozens of museums and universities, with $12 million from the National Science Foundation. Once online, this valuable resource can

unleash waves of discovery, tackling big questions, from the evolutionary paths of species to the future impacts of climate change. As an online resource, it will be open to anyone from a student interested in dinosaur fossils to a molecular geneticist interested in adaptations in a species.

In the $10 million Center for Compressible Multiphase Turbulence, Bala Balachandar and his colleagues are investigating problems of predictive and simulation science using the most powerful computing platforms available. The simulations the team has in mind will require computers so powerful they don’t even exist — yet. UF scientists, in collaboration with industry and NSF, are working on the computer of the future, capable of running the most complex simulations of explosions, volcanic eruptions and supernovae.

And in the Clinical and Translational Science Institute, a team is studying health and disease by following the trails of molecules called metabolites, previously undetectable, but now revealed with increasingly powerful imaging and computing

power. Metabolites convert food into energy and allow communication between cells, tissues and organs.

They provide a unique means of studying health.

UF launched its Southeast Center for Integrated Metabolomics in 2013 with a five-year, $9 million grant from the National Institutes of Health.

The capacity to collect, store and analyze vast troves of information will be essential to scientific inquiry and, in fact, represents a revolution. Instead of asking a question and gathering data, scientists can now look for patterns in data that will help them ask better, bigger questions.

Data itself isn’t wisdom.

Our researchers tease it out, using computers to take on complex challenges in engineering, education, science and health care. We have the computing horsepower and the brainpower to be a national leader in data science and analytics. Because we already have one of the nation’s most wide-ranging research portfolios, UF has tremendous potential to use computers to improve people’s lives in numerous ways.

Institute of Food and Agricultural Sciences

RESEARCHERS JOIN WITH WATER MANAGEMENT DISTRICT TO STUDY SPRINGS management of nitrates flowing into the springs;

THE UNIVERSITY OF FLORIDA’S Institute of

Food and Agricultural Sciences is joining forces with two entities as part of a $3 million, three-year contract to provide scientific data to help protect and restore the state’s springs system.

UF/IFAS’ partners in the effort are the St. Johns River Water Management District, which is funding the project, and UF’s Water Institute.

“The state of Florida and the St. Johns district have made protection of Florida’s springs one of their highest environmental priorities,” said Hans G. Tanzler III, the St. Johns district’s executive director. This collaboration between the district and UF will develop the strong scientific foundation needed to focus resources to achieve the maximum benefit of restoration and protection.”

The funding comes from the St. Johns district’s Springs Protection Initiative, which combines science, projects, planning and regulatory programs to reduce nitrate loading and protect spring flows. The partnership’s primary focus will be on the Silver Springs springhead and ecosystem, including: • Improving the scientific foundation for the

• Evaluating whether nitrate reduction alone will be sufficient to restore the balance of nature; • And assessing the influence of other pollutants and stressors.

Scientists will also look at rainfall and runoff quantity and quality; aquifer storage, flow and spring discharge; nitrate sources, nitrate uptake and nitrate loss in soils and groundwater; how the springs function and algae abundance.

A second system slated for in-depth research will be the Wekiva Springs system in Apopka, which sits at the headwaters of the Wekiva River – one of two National Wild and Scenic Rivers in Florida.

“Focusing the best water researchers in Florida on this issue will allow us to take the next major step toward the ultimate protection of these jewels in the state’s crown,” said Jack Payne, UF senior vice president for agriculture and natural resources. “This collaboration will develop the strong scientific foundation needed to restore and protect Florida’s world-class springs.”

Florida has one of the largest concentrations of freshwater springs on Earth,

BIG DATA Milestones

with more than 700 bubbling up from the state’s aquifer. There are 96 springs within the SJRWMD, including Silver Springs.

The springs’ crystal-clear water, which maintains a year-round temperature of 72 degrees, is the source for many of North and Central Florida’s rivers and streams, providing habitat for wildlife and fish, including manatees, alligators, limpkins, herons and turtles.

Water Institute Director Wendy Graham noted that the program involves 10 Water Institute-affiliated faculty.

The research is lead by K. Ramesh Reddy, chair of the soil and water science department and Ed Lowe, SJRWMD’s chief scientist.

Reddy noted that UF has partnered with SJRWMD for four decades on various projects involving management and restoration of ecosystems within the St. Johns River basin.

“Florida’s springs serve as living laboratories to provide invaluable opportunities to understand more fully the complex processes regulating the health of these fragile ecosystems,” he said.

“FOCUSING THE BEST WATER RESEARCHERS IN

FLORIDA

ON THIS ISSUE

WILL ALLOW US TO TAKE THE NEXT MAJOR STEP TOWARD THE ULTIMATE PROTECTION OF THESE JEWELS IN THE STATE’S

”

CROWN.

— JACK PAYNE

Ramesh Reddy, krr@ufl.edu

Kimberly Moore Wilmoth

1956 – An IBM 650 CPU, the world’s

first mass-produced computer, is installed at the University Statistical Center. It could process 1,000 instructions per second.

Explore

5

College of Medicine

GENE THERAPY OFFERS POTENTIAL TO STOP MULTIPLE SCLEROSIS IMMUNE RESPONSE

“EVERYONE HAS DIFFERENT TYPES OF

T

REGULATORY CELLS AND RECEPTORS.

BY

INJECTING

A GENE RESPONSIBLE FOR A BRAIN PROTEIN, WE ARE ALLOWING AN INDIVIDUAL’S BODY TO MAKE THE SPECIFIC

T

REGULATORY

”

CELLS IT NEEDS.

— BRAD E. HOFFMAN

IN PATIENTS with multiple sclerosis, the body turns on itself, launching an immune system attack that destroys the coating around nerve fibers in the central nervous system, leaving them exposed like bare wires.

Similar to exposed electrical lines, the unprotected fibers touch and short out, leading to the neurodegenerative effects that are a hallmark of multiple sclerosis.

But what if doctors could stop the immune response that destroys the protective coating before the disease becomes debilitating? University of Florida researchers have received a $40,000 grant from the National Multiple Sclerosis Society to test a gene therapy technique in mice that aims to help the body re-establish immune tolerance in the early stages of the disease.

“In previous years, we have learned a lot about how to manipulate tolerance using gene therapy,” said Brad E. Hoffman, an assistant professor of pediatrics in the UF College of Medicine. “Tolerance is your body’s way of not responding to substances that would otherwise induce an immune response so

1967 – An IBM 360/50, which could process 178,000 instructions per second, is installed. On Dec. 6 the UF Computing Center ran 504 jobs, a new record.

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Summer 2014

you don’t have an immune response to everything. In multiple sclerosis, the body loses that ability to distinguish between self and notself so it starts to attack its own nervous system cells.”

About 2.3 million people worldwide suffer from multiple sclerosis. The disease typically causes problems with vision, fatigue, speech, sensation and mobility. In advanced cases, multiple sclerosis can lead to blindness and paralysis.

Typically, gene therapy is used to correct a faulty gene in the body. In this case, researchers will deliver a gene responsible for a brain protein into the liver, via the harmless AAV virus, in hopes that it will spark production of regulatory T cells. These T cells, which suppress the immune system, are crucial because they could effectively shut down the immune attack in the brain. The researchers are injecting the gene into the liver because the organ filters out unwanted immune responses.

“Everything filters through the liver for detoxification,” Hoffman said.

“Because of this, the liver has an innate capacity to induce immune tolerance.

We have learned in other gene therapy studies that it is possible for the liver to make cells tolerant to the gene you are putting in.”

The UF researchers’ work is novel because they hope to develop a technique that could be used on a wide number of patients.

“Everyone has different types of T regulatory cells and receptors,” Hoffman said. “By injecting a gene responsible for a brain protein, we are allowing an individual’s body to make the specific T regulatory cells it needs.

“If it works, this is potentially more clinically feasible, cost-effective and translatable for a large scale.”

Although gene therapy has yet to be used to correct autoimmune disorders, the foundations for the study are rooted in research Hoffman’s team performed while studying gene therapy for hemophilia. The team was able to induce immune tolerance in mice, and Hoffman hopes the techniques will help people with multiple sclerosis, too.

“Will we be able to cure MS? That would be ideal, but our strategy is more likely to result in suppressing the immune response to the nervous system,” he said.

“If you suppress the immune response, you will suppress the neurodegenerative effects and hopefully maintain a higher quality of life.”

Brad Hoffman, bhoffman@ufl.edu

April Frawley

BIG DATA Milestones

College of Veterinary Medicine

GOLD-BASED DRUG FIGHTS BONE CANCER IN PEOPLE AND PETS A GOLD-BASED drug

1972 – The UF Computing Center becomes the Northeast Regional Data Center of the State University System of Florida. An IBM 370/165 is installed which could process 1,890,000 instructions per second.

years, however, aurothiomalate has been investigated for its potential effects against certain types of cancer.

The UF study is the first to focus on the drug’s effectiveness as a tool for possible canine bone cancer treatment through petri dish tests and in vivo studies in mice.

They found that low doses of the drug significantly reduced cancer spread to the lungs — the site to which osteosarcoma most frequently travels in dogs.

High doses reduced microscopic spread to the lungs and the incidence of tumor cell clusters within blood vessels.

Further study is needed to better understand how aurothiomalate works against osteosarcoma cancer cells, and to better determine effective dose ranges before extending this research to dogs, the researchers said.

“One of the interesting things to me in studying oncology and our pets is that their disease often translates to human disease as well,” Scharf said.

“Therefore, research on the animal side can potentially translate to human medicine as well.”

“THIS STUDY SHOWS THAT THERE IS POTENTIAL PROMISE FOR THE ROLE OF GOLD DRUGS AS A PART OF BONE CANCER TREATMENT IN DOGS AND POTENTIALLY

”

IN PEOPLE.

—

VALERY SCHARF

Sarah Carey

currently used in human and veterinary medicine to manage certain immune diseases may prove useful in combating osteosarcoma, a devastating bone cancer that affects both dogs and people, University of Florida veterinary researchers report.

By examining an aggressive bone cell line in both species, the researchers found that the drug, aurothiomalate, commonly known as gold salts, kept cancer cells from forming in the laboratory.

“We also were able to demonstrate that the drug slows tumor growth and decreases metastasis when canine bone tumors were created in a mouse model,” said Valery Scharf, the study’s lead author. A small animal surgery resident at UF, Scharf completed her master’s degree last year.

The research was the focus of her thesis.

The findings appear in the journal Anti-Cancer Drugs.

“This study shows that there is potential promise for the role of gold drugs as a part of bone cancer treatment in dogs and potentially in people, although more studies are needed before we can use them in a clinical setting,” Scharf said.

Osteosarcoma is the most common primary bone tumor found in dogs and accounts for the

vast majority of cancerous tumors — around 80 percent — in the canine skeleton. The condition occurs most commonly in large-breed dogs that are middle-aged and older. The cancer frequently appears in the front leg, but it can occur in any bone. Dogs with osteosarcoma often show signs of lameness in the affected leg.

Veterinarians typically amputate the affected limb to remove the primary tumor. Dogs can also receive chemotherapy if the cancer has spread. However, some dogs aren’t candidates for amputation, and the decision to amputate can be difficult for pet owners.

In people, osteosarcoma is rare and also affects the long bones of the body. It typically is diagnosed in people under 25 years of age.

“Osteosarcoma is a frustrating disease, as you can treat the local tumor but the metastasis is something there is no effective means of preventing,” Scharf said.

The use of gold compounds in human medicine has traditionally been based on gold’s ability to affect the body’s immune response and anti-inflammatory properties, with the primary use being the management of rheumatoid arthritis. In veterinary medicine, gold-based drugs are most commonly used to treat various autoimmune disorders. In recent

Valery Scharf, vscharf@ufl.edu

Sarah Carey

1978 – The Florida Computer Crimes Act is passed.

Explore 7

College of Liberal Arts and Sciences

SEA SNAKES NEED FRESH WATER FOR DRINKING

“ WE THINK THEY ALMOST CERTAINLY KNOW THAT IT RAINS BECAUSE THEIR BEHAVIOR CHANGES DURING THE APPROACH OF A TROPICAL STORM AS THE ATMOSPHERIC PRESSURE

”

CHANGES.

— HARVEY LILLYWHITE

1985 – The first laser printers are installed for letter-quality output.

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Summer 2014

A LTHOUGH they spend their lives surrounded by water, sea snakes dehydrate for months at a time, waiting to quench their thirst with fresh water from rainfall, a University of Florida biologist has found.

The finding contradicts the accepted belief that marine vertebrates have evolved to use salt water to meet their water requirements, said Professor Harvey Lillywhite, whose research appeared in the Proceedings of the Royal Society B, the flagship biological research journal of the Royal Society.

“These snakes refuse to drink salt water, even when dehydrated,” Lillywhite said.

“They need fresh water to survive.”

Current physiology textbooks state that marine reptiles drink sea water, distilling the water by excreting excess salt via salt glands.

While it is true that they excrete salt, Lillywhite said, “no sea snake we have tested drinks sea water.”

The findings are the result of three years of field studies of the Yellow-bellied Sea Snake, the most widely distributed pelagic sea snake, which inhabits tropical oceans. Lillywhite and his colleagues also studied the sea snakes in the laboratory.

Both in the field and in the lab, sea snakes shunned salt water, taking a drink only when fresh water was

available. At sea, sips of fresh water depend on rainfall.

Rainfall is less dense than sea water, so it floats on the surface, forming a “lens” of fresh water. Such layers of water may persist as fresh water or dilute brackish water at the ocean surface for days, but snakes probably drink the rainwater during or shortly after a rainstorm. In lagoons, where sea snakes often are abundant, a fresh water lens might persist longer than one in the open ocean.

The snakes appear to sense rainfall.

“We think they almost certainly know that it rains because their behavior changes during the approach of a tropical storm as the atmospheric pressure changes,” Lillywhite said.

During or after a rain, the snakes, which spend most of their time deeper in the water, surface to take a sip of fresh water. The Yellow-bellied Sea Snake, Lillywhite said, consumes varying quantities, from small amounts up to 25 percent of its body mass when fresh water is available.

The open ocean is a virtual desert, especially during the dry season, which can last six or seven months at Guanacaste, Costa Rica, where the snakes were studied, Lillywhite said. During that time, sea snakes slowly dehydrate, and lose up to 25 percent of their body mass, a level that would be “way past lethal for a human,” Lillywhite said.

Lillywhite said diminishing rainfall might be the cause of declining populations of sea snakes in some areas, such as droughtstricken Northern Australia, where sea snake populations have declined for 10 years and two local species are thought now to be extinct.

If global climate change causes drought conditions to worsen, sea snakes and other marine vertebrates that depend on rainfall for fresh water could be hurt, Lillywhite said. There are more than 60 species of entirely marine sea snakes and eight species of sea kraits that live in the sea but spend some time on shore. Lillywhite’s study also raises the question of whether other marine species might depend more on fresh water than previously thought.

An interesting follow-up, he said, would be to study sea turtles — which live in salt water and have a broad distribution similar to the pelagic species of sea snake — to determine if they depend, even partially, on fresh water.

“Understanding the water requirements and drinking behaviors of marine vertebrates could help with conservation efforts,” Lillywhite said. “In areas of intensifying drought, they will need to move or die out.”

Harvey Lillywhite, hblill@ufl.edu

1988 – The last

card reader is removed.

NERDC connects to the Internet.

Cindy Spence

Institute of Food and Agricultural Sciences

BURMESE P YTHONS CAN NAVIGATE HOME FROM MILES AWAY IF YOU pick them up and drop them in a new location, most snakes will move rapidly but erratically, often traversing the same terrain before giving up and settling into their new digs.

Burmese pythons aren’t most snakes.

A team of researchers including scientists from UF’s Institute of Food and Agricultural Sciences has discovered that the giant snakes — which have invaded and affected the food chain in Everglades National Park and Big Cypress National Preserve — can find their way home even when moved more than 20 miles away.

The findings change how researchers understand python behaviors and intellect.

“This is way more sophisticated behavior than we’ve been attributing to them,” said Frank Mazzotti, a wildlife ecology and conservation professor based at the Fort Lauderdale Research and Education Center. “It’s one of those things where nature makes us go ‘wow.’

That is truly the significance of this.”

In 2006 and 2007, researchers captured 12 pythons and surgically implanted radio transmitters that allowed them to track the snakes’ movements. As a control group, they returned six of the snakes to the spot

of their capture and turned them loose.

The remaining six snakes were taken to spots ranging from 13 to 22 miles away from where they had been captured and turned loose.

To the researchers’ surprise, the snakes oriented themselves toward “home” and maintained their bearings as they traveled.

And although it took between 94 and 296 days for five of the six snakes to get within three miles of home, partly due to it being the snakes’ dormant season, the reptiles kept that orientation — a clear signal to scientists that the snakes have both “map” and “compass” senses.

The relocated snakes appeared to use local cues at the release site to understand their position relative to home (the map sense), and appeared to use cues along the way (their compass sense) to ensure that they remained on track, although the researchers don’t yet know what those cues are: smell, perhaps the stars, light or some kind of magnetic force.

Mazzotti said it’s interesting for researchers to know that the snakes move purposefully through their environment, but in reality, it’s not that much help.

“It amps up a little bit our concern about the snakes, but given all the

1989 – Wordperfect 4.2 is installed for testing.

other things we know about pythons, the amount of increasing concern is minor,” he said.

The Burmese python has been an invasive species in South Florida since about 2000, likely stemming from accidental or purposeful releases by former pet owners. The largest python found in the Everglades area had grown to more than 18 feet.

The snakes suffocate and eat even large animals, such as deer and alligators, and in 2012, a research team that included Mazzotti found severe declines in python-heavy areas of native animals including raccoons, opossum, bobcats and rabbits.

In 2012, the federal government banned the import and interstate trade of four exotic snake species: the Burmese python, the yellow anaconda, and North and South African python.

A link to frequently asked questions: http://

A

TEAM OF RESEARCHERS ,

INCLUDING SCIENTISTS FROM OF

UF’S INSTITUTE

FOOD

AND

AGRICULTURAL SCIENCES, HAS DISCOVERED THAT THE GIANT SNAKES CAN FIND THEIR WAY HOME EVEN WHEN MOVED MORE THAN

20

MILES AWAY.

www.usgs.gov/faq/ categories/10721/4751

Frank Mazzotti, fjma@ufl.edu

Mickie Anderson

1995 – IBM scalable POWERparallel SP2

UNIX-based NERSP supercomputer is installed.

Nearly 100 28.8 modems are installed.

Explore 9

Institute of Food and Agricultural Sciences

SPACEX DRAGON TAKES UF PLANTS TO SPACE STATION FOR GROWTH STUDIES A UNIVERSITY OF FLORIDA science project

“ WE ARE INTRIGUED BY THE NUMEROUS LIGHTSENSING GENES THAT ARE EXPRESSED SPECIFICALLY IN ROOTS IN ORBIT, AND THE

SPACEX-3

EXPERIMENT

FURTHER EXPLORED THE ROLE OF THESE GENES IN ORIENTATION AND CELLULAR

”

REMODELING.

— ANNA-LISA PAUL To learn more visit ufspaceplants.blogspot.com

BIG DATA Milestones

10

Summer 2014

that rocketed to the International Space Station on April 18 aboard the SpaceX-3 Dragon is focused, literally, on what it takes for biology to adapt and thrive in space.

The experiment by plant molecular biologists Robert Ferl and Anna-Lisa Paul uses small plants as models to understand cellular responses to spaceflight.

This experiment, known as CARA, is a follow-up to research they conducted on the ISS in 2010 which found for the first time that roots display normal movements used to get around rocks and obstacles even when there is no gravity.

The movements, known as waving and skewing, were thought to be due to cellular responses to gravity pulling on roots as they sample their growing surface with touch, Paul said.

“But as the images from our experiment started to come down from the International Space Station in early 2010, it was clear that gravity was not required after all,” she said.

Based on the 2010 results, Paul and Ferl wanted to see if, in the absence of

gravity, perhaps the plants were responding to another directional cue, such as the overhead light source integrated into the plant growth hardware. Such alternate signal processing by the plant cells would indicate that biology explores unique adaptive strategies when in novel circumstances.

“We are intrigued by the numerous light-sensing genes that are expressed specifically in roots in orbit, and the SpaceX-3 experiment further explored the role of these genes in orientation and cellular remodeling,” Paul said. “It is likely that light plays a more important role in root growth in microgravity than it does on Earth.”

And that has big implications for life somewhere other than Earth, Ferl said.

“This is telling us that life utilizes special, potentially unique signals to adapt to living off planet,” he said. “This has tremendous implications for the expansion of human existence to other worlds, but also richly informs us about the potential for plants to adapt to unusual environmental changes here on Earth.”

Ferl and Paul worked with NASA engineers at Glenn Research Center (GRC) in Ohio to adapt the Light Microscopy Module (LMM) for biological applications in order to focus the analysis on the cells that

normally sense gravity in plants.

The LMM is a sophisticated fluorescent microscope facility housed on the ISS, with a counterpart at GRC, that has historically been used for physics experiments. The plants of the CARA experiment are grown in square petri plates on a nutrient agar matrix, and in this experiment simply attached to the wall of the US module of the ISS. During the course of the CARA experiment the plates were photographed in place with a standard camera, but in addition, the plate containing plants engineered with fluorescent reporters was examined with the LMM to evaluate spaceflight-associated changes in the cellular localization of selected genes.

An astronaut inserted the plate into a specially adapted holder on the onorbit LMM, then Paul and Ferl worked with the GRC engineers to control the use of the microscope telemetrically from the ground.

The experiment was sponsored as a research grant to Paul and Ferl by the Center for the Advancement of Science in Space (CASIS), the Florida-based national organization responsible for promoting science on the ISS. Rob Ferl, robferl@ufl.edu Anna-Lisa Paul, alp@ufl.edu

1998 – UF President John Lombardi announces computer requirement for all students.

McKnight Brain Institute

“LOBSTER R ADAR” MAY BE KEY TO BETTER ELECTRONIC SENSORS COULD LOBSTERS help protect soldiers someday?

A team of University of Florida researchers says they might.

Don’t expect to see battlefields filled with spiny crustaceans on leashes, though. The secret lies in how the clawed creatures locate a specific scent. UF Health researchers and engineers say they have identified the neurons involved in that ability — call it “lobster radar” — and that discovery may help them develop improved electronic “noses” to detect landmines and other explosives.

“An electronic nose has to recognize an odor and locate its source. Finding the source has often been the job of the person handling the electronic nose,” said Barry W. Ache, distinguished professor of neuroscience and biology and director of the Center for Smell and Taste in UF’s McKnight Brain Institute.

To date, the technology has had its drawbacks — especially when the nose is used to detect potentially deadly materials that could endanger its human handler.

Yuriy V. Bobkov, of the UF Whitney Laboratory for Marine Bioscience, originally discovered a type of olfactory neuron in lobsters that constantly discharges small bursts of electrical pulses, much like radar uses pulses of radio energy to

detect airplanes or thunderstorms. UF researchers speculated that these so-called “bursting” neurons might cue the crustaceans in on an odor’s location — especially important when they are searching for food or trying to avoid danger.

Odors exist as compounds that move through the air or water and settle on olfactory neurons in “whiffs.” The time between whiffs depends on the distance between the smeller and the source of the smell.

Sensing the time intervals allows animals to determine the location of an odor.

That’s where bursting olfactory neurons from lobsters come in.

To try to solve the mystery of how lobsters process sensory information, José C. Príncipe and Il Memming Park, of the Computational NeuroEngineering Laboratory in UF’s Department of Electrical and Computer Engineering, took information gleaned from these cells and created a computational model.

Each bursting cell responds to a whiff at a different frequency, Ache said. Together, the neurons help pinpoint the location of a particular odor. Just as a person can hear a train moving from left to right, a lobster’s set of olfactory neurons set the scene for the location of a smell.

2008 – The world’s largest computing grid, pioneered in part by UF researchers, is launched to crunch the mammoth amounts of data produced by the Large Hadron Collider particle accelerator in Europe.

By entering the lobster olfactory data into a computer model and giving artificial silicon neurons the same features found in the crustacean ones, then subjecting the neurons to simulated whiffs of odor, the researchers could determine how the bursting neurons function and how they set a scene that tells the animal the source of a smell.

“These cells as a population seem to provide a system for detecting odors in the spatial world,” Ache said. “We hope not only to learn more about how these systems work, but how that information might be applied to challenges such as electronic noses.”

In addition to improving electronic sensors, this finding will help scientists better understand the sense of smell in all animals — including humans.

“The involvement of bursting sensory neurons in olfactory processing is not unique to the lobster,” Bobkov said. “It’s likely to be a fundamental aspect of olfaction.”

The team reported the findings in the Journal of Neuroscience.

“AN

ELECTRONIC NOSE

HAS TO RECOGNIZE AN ODOR AND LOCATE ITS SOURCE.

FINDING

THE

SOURCE HAS OFTEN BEEN THE JOB OF THE PERSON HANDLING THE ELECTRONIC NOSE.”

— BARRY W. ACHE

Barry Ache, bwa@whitney.ufl.edu

Melissa Lutz Blouin

2013 – UF unveils the state’s most powerful supercomputer, with a peak speed of 150 trillion calculations per second.

Explore 11

Harnessing the Power of Predictive Science

By Cindy Spence

Imagine

trying to recreate the eruption of Mount St. Helens or the collapse of the World Trade Center.

“Sometimes, experiments are not an option,” says UF mechanical and aerospace engineering Professor Bala Balachandar.

And even if he could simulate such complex events in the lab, Balachandar says there is currently no computer capable of fully analyzing the flood of data.

But Balachandar and his team are out to change that, with the support of a five-year, $10 million grant from the National Nuclear Security Administration.

Balachandar’s field of predictive simulation science is like looking into a crystal ball. It takes the known behavior of atoms and molecules — which can be expressed through mathematical equations — and applies them to unknown events, like the

chaos of massive explosions — natural or man-made.

It’s easy to understand why a nuclear security agency would be interested in such capabilities, but Balachandar says the practical applications of being able to simulate such complex events go far beyond nuclear devices.

Predictive simulation science grew out of the nuclear test bans of the 1990s. The bans put national nuclear labs in a bind: how do you certify a nuclear warhead is serviceable if you can’t test it? Scientists developed computational surrogates for nuclear testing, and in the process found those models useful in studying other complex phenomena that can’t be tested in a lab, like supernovae and volcanic eruptions.

Taking a complex process and converting it to a computational model is tricky. A model must be detailed enough to account for many variables

Photography by John Jernigan; Illustration by KD Kinsley-Momberger

so that an accurate prediction can be made. Too much detail, however, and the model collapses under the weight of its own data.

“My back-of-the-envelope calculation is not very accurate,” Balachandar says. “On the other hand, if I have an equation for every molecule it would take 100 billion years to predict what’s going to happen, and that is not useful. So we have to strike a sweet spot.”

In the case of nuclear weapons, Balachandar says, the model should be detailed enough, for example, to tell the President of the United States, “You can make a decision based on my simulation, because I trust my answers.” Or, if the issue is an impending volcanic eruption, the simulation should be detailed enough that an emergency management official can decide when and how far to evacuate.

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13

Hurricane forecasting is a predictive science success story, Balachandar says, noting that 50 years ago hurricanes in India caused huge losses of life. A hurricane just last year in India caused fewer than 10 deaths.

Balachandar points out that predicting a hurricane’s strength at somewhere between category 1 and category 5 is not useful, but a prediction with 95 percent certainty that a hurricane will be category 5 provides information that is useful.

Scientists won’t make the decisions, but they can give decisionmakers an answer they can use in their deliberations.

“Simulation allows people to make better decisions,” Balachandar says.

“We reduce the guesswork by bringing in as much physics and computational power as possible.”

As a big data challenge, Balachandar says, simulating complex phenomena is so data intensive that it requires the world’s largest, fastest computers, and then some.

The best computers today operate at petascale, performing a quadrillion — a thousand trillion — calculations every second. Imagine a desktop computer with a quad core; put 250,000 together and you have a million cores, and can do petascale calculations. In the quest for greater precision and speed in simulations, Balachandar says scientists are eyeing the next generation — exascale computers.

“Which don’t exist and won’t for many years,” says Alan George, the lead computer scientist on the team and a professor of electrical and computer engineering.

George and colleagues Herman Lam and Greg Stitt and a team of

14 Summer 2014

“

Simulation allows people to make better decisions. We reduce the guesswork by bringing in as much physics and computational power as possible.

— Bala Balachandar

”

In previous experiments, Balachandar and his collaborators modeled complex multiphase turbulence in an oceanic environment, shown above.

students at CHREC, the National Science Foundation Center for HighPerformance Reconfigurable Computing at UF, are tackling the problem of computing power for simulation science. Down the hall from George’s office sits the Novo-G, the most powerful reconfigurable computer in the world. The reconfigurability of the Novo-G represents a dramatic departure from the trend of present computer architectures, but even the Novo-G is not exascale.

In the past, science could anticipate the growth of computing power using Moore’s Law, which forecast that computing power would double roughly

every two years. But with petascale computing, a milestone reached five years ago, Moore’s Law is reaching its limits, making exascale the holy grail of computing, at least for now.

In theory, all you’d have to do is string 1,000 petascale machines together and you’d have exascale. But you’d need one nuclear power plant to run that many machines, Balachandar says, and another nuclear power plant to cool them.

Balachandar and the physics team have all kinds of “wonderful ideas about how to make their simulations more accurate, more detailed, more sophisticated, more robust,” George

says, so the computer scientists learn how their applications function and try to develop a new computing architecture to support them.

“These are very complex simulations, and to perform them in a response time shorter than your lifespan you need more and more powerful computers,” George says. “If you were to look at all the supercomputers in the world, that’s what most of them are being used to do; some are simulating Earth climate, others are simulating multiphase turbulence, and so on. Supercomputers are widely used to study and solve problems so computationally intensive that the most

powerful computers in the world are necessary to do it.”

George’s team is charged with the task of studying and evaluating ways to build and use the exascale computer of the future — what Balachandar calls a “grand challenge” — and George says such challenges are natural in computing.

“Before exascale was Mount Everest, petascale was Mount Everest, and before that terascale,” George says. “So now exascale is the next big challenge.”

The road to exascale computing is fraught with unprecedented difficulties. Pursuing exascale computing in the traditional manner — by

connecting a thousand petascale machines — doesn’t make sense, George says. Each petascale machine costs hundreds of millions of dollars, is as big as a building, and generates so much heat that its cooling bills alone run $1 million a month.

“That just doesn’t make sense, economically, practically or technically,” George says. “Because of that, exascale is really opening up new research challenges. How do we design systems in new and better ways than we ever have before?”

In the early days of computing, the machine was the main cost. Then software became the main cost. Now,

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“

These are very complex simulations, and to perform them in a response time shorter than your lifespan, you need more and more powerful computers.

— Alan George

”

Alan George, Gregory Stitt and Herman Lam are tackling the task of developing new computing architectures. Here, they are shown with a 3-D graphical rendering of a petascale machine at the National Science Foundation Center for High-Performance Reconfigurable Computing at UF.

George says, one day, maybe not too far away, energy may become the dominant cost in computing.

“If we’re already spending a million dollars a month on utility bills for some of these machines, just imagine what that might be with exascale if we don’t find a better way to do things,” George says.

George is just the man for the job.

As recently as 2004, there wasn’t a centralized campus computing infrastructure, but there was a big appetite for it. George chaired a committee that convinced units from all across campus – health, agriculture, liberal arts and engineering – to pool their resources, and high-performance computing at UF took hold.

George moved on to CHREC and reconfigurable computing, and for some applications, the Novo-G is the

16 Summer 2014

fastest computer in the world. The one-size-fits-all architecture of a conventional computer doesn’t change, whether it is used for word processing or sequencing a genome. In reconfigurable computing, the architecture changes to suit the need, and that delivers faster processing at a lower energy cost.

The potential of the Novo-G has drawn interest from more than 30 industry partners.

George points out that the traditional style of expanding computing power has pitfalls. As processors and chips get smaller and more and more are added, the system grows ever more complex, meaning more can go wrong, and then reliability becomes an issue.

“All of these things are daunting,” George says. “Nobody really knows

the best way to study something that doesn’t exist. Balachandar studies things you can’t actually build and test, and we are as well.”

Balachandar says the point is to co-design: do what can be done at petascale, while developing methods that will work at exascale.

Already, the team is using UF’s new HiPerGator computer to develop codes, test them, run cases and finetune formulas before hopping on to even more powerful computers at the national labs, and, eventually, the exascale machines of the future.

“Traditionally, we scientists work on existing machines and then a new machine comes out and we scramble for three years to change our code to work on the new machine, then guess what. The next machine comes out, and by the time we learn to use that

COMPUTING BY THE NUMBERS 1,000,000 MEGA

PETASCALE COMPUTING

1,000,000,000 GIGA 1,000,000,000,000 TERA

Computing power equal to 250,000 desktop computers

$1 Million cooling bill per month

A petascale computer is as big as a BARN

1,000,000,000,000,000

PETA

1,000,000,000,000,000,000

EXA

EXASCALE COMPUTING TWO nuclear power

plants are necessary for an exascale computer.

One to power and one to cool.

An exascale computer will be 1,000 times FASTER than today’s most powerful supercomputer.

Computing Power OPERATIONS

PER SECOND

one ... so this co-design strategy is a paradigm shift.”

Revolutionizing the processing of the gigantic datasets for simulations will lead to discoveries in many other fields as well, Balachandar says.

“We’re doing something based on a future, non-existent technology, to move science forward,” Balachandar says. “This is great, this is awesome.”

Bala Balachandar Professor of Mechanical & Aerospace Engineering balas1@ufl.edu Alan George Professor of Electrical and Computer Engineering george@hcs.ufl.edu Related websites: https://www.eng.ufl.edu/ccmt/ http://www.chrec.org/

CENTERS OF EXCELLENCE The University of Florida was chosen for one of the centers in the Predictive Science Academic Alliance Program II (PSAAP II), funded through the National Nuclear Security Administration.

The interdisciplinary teams from six universities will be at the leading edge of computing innovation to address the world’s most complex problems.

The universities are: • University of Florida • Stanford University • University of Illinois – Urbana-Champaign • University of Utah • Texas A&M University • University of Notre Dame

The UF team is: • S. “Bala” Balachandar • Alan D. George • Raphael T. Haftka • Sanjay Ranka • Nam-Ho Kim • Herman Lam • Gregory Stitt • Siddharth Thakur • Thomas L. Jackson

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18 Summer 2014

iDigBio is revealing new research opportunities in long-hidden museum collections

BY CINDY SPENCE Photography by Kristen Grace

arry Page would like to get back to his fishes, the catfish and loaches he studies as a University of Florida ichthyologist, but first he and his colleagues have some work to do on plant, animal and fossil specimens — millions of them.

Page and an army of helpers are on year three of iDigBio, a 10-year, $12 million effort to digitize the biological specimens tucked away in museum collections across the country. He estimates there could be 1 billion nationally, representing the collected knowledge of biological diversity for vast swaths of the planet.

Although it has taken him away from his fishes, the effort already has contributed to his work in an unexpected way.

“A student and I just found a database where specimens of a loach have been collected in Pakistan,” Page says.

“We thought these loaches only went as far west as India, but there they were, in Pakistan.”

Such moments of discovery can be rare. Scientists can labor long stretches between them, sometimes whole careers without them. But with iDigBio, Page says, “these aha! moments

could almost be routine; that’s what this is all about, and it is happening all the time.”

Centuries of knowledge are stored in museum collections around the country, from a fern collected, pressed and labeled hundreds of years ago, to an insect collected just last year. For taxonomists and other scientists, finding these specimens can be daunting.

“There are specimens that have been around for 100, 200 years, but they’ve been in a drawer somewhere, and it’s hard to know where everything is,” says Page, the director of iDigBio. “If it’s online, you can touch a button and find in seconds what it might have taken you a lifetime career to know was there.”

By the most recent estimate, humans share the Earth with 8.7 million other life forms. Species are being lost and discovered all the time, but even with all the collected knowledge, much, much more remains to be learned. Scientists estimate that 86 percent of land plants and animals and 91 percent of those in the sea have yet to be identified.

Lately, says researcher Pamela Soltis, those discoveries are in specimen drawers.

“Most species discoveries are actually made in museums, not in the wild, anymore,” says Soltis, who studies molecular systematics and evolutionary genetics as distinguished curator at the Florida Museum of Natural History.

The specimen drawers in most museums are a treasure trove. In most cases, only a tiny fraction of what a museum owns is on display.

In storage, sometimes a specimen is overlooked, sometimes not correctly named or well-described. The beauty of keeping it all is that a second look, years later, by a student or a scientist, can uncover an entirely new species.

Armed with new methods, like genetic sequencing, new discoveries can be made, or a gap in an evolutionary path filled. Digitizing that information could speed up the pace of such discoveries. The tree of life, Soltis says, could be way more complex than we think it is.

“There’s more information about biodiversity in museum collections than any other place — except nature itself,” adds Page, “but the problem is, it’s really difficult to get.”

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iDigBio

14 MILLION

We share the Earth with

8.7 MILLION

specimen records

Other Life Forms

86% • LAND plants & animals 91% • SEA plants & animals

1 BILLION estimated # of biological specimens tucked away in collections nationally

2 MILLION specimen images

A L R E A DY ONL INE!

YET

to be identified

Scientists who want to examine specimens outside their institution must travel far and wide, generally to several institutions. Alternatively, they can ask for a loan, which means someone at the host institution must pull the specimens off shelves, wrap them up, box them and ship them. There are other issues, too, with a loan. The institution receiving a loan must have the facilities to properly store it, and of course, things can go wrong in shipping.

Loans, Page says, are never quite satisfying because they leave you wondering what else might be there. And the most valuable specimens, the primary types — the specimens used to validate the name of a species — are so precious that often a museum will not loan them at all.

Putting this treasure online opens it to research, education and just plain curiosity. Both the specimen and

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the traditional label information are digitized, sometimes along with other information, such as the audio of Cornell University’s bird songs. Using the label data alone, a scientist can produce maps showing, for example, the range of an organism or change in its distribution over time.

The National Science Foundation is funding digitization of museum and university collections to the tune of $100 million over 10 years as part of its Advancing Digitization of Biodiversity Collections program, with iDigBio coordinating the national effort.

So far, 156 collections, representing all 50 states, are participating. Museums and universities are grouped into thematic collections networks, which work together to digitize information on a particular research topic, for example insects that feed on plants.

Museum collections are being added

all the time, most recently the Field Museum in Chicago for its insects and Appalachian State University in North Carolina for its herbarium specimens.

The digitization effort is massive, and that’s where citizen scientists can help, Page says. Hobbyists, for example, could input the label data.

Two different people would enter the data and a computer would cross reference it, so if there’s any discrepancy a specialist would know to take a look at that file.

Already 14 million specimen records and 2 million images are online, accessible from a search portal developed by UF’s Advanced Computing and Information Systems Laboratory (ACIS). The data so far fit into banks of computers the size of two refrigerators in the ACIS lab.

As a big data project, iDigBio certainly qualifies. But José A.B. Fortes,

Historically, scientists kept their data in field journals like this one from the 1930s, requiring a collaborator to visit a museum or arrange a loan to do research. When the specimen image and collection data go online with iDigBio, the digitized information is available globally, both for research and education.

the computing director for iDigBio, says there are issues beyond size. The variety of the data and the differences in how data are recorded and input from institution to institution make it a thorny computing problem.

Something as simple as a date can be entered different ways: day first, month first, or year first, using numbers, using names. The storage essentially is a resource problem, one that money solves. The others can be tricky.

“There are challenges in the heterogeneity of the data, heterogeneity of practices and the degree to which different folks feel comfortable with different technologies,” says Fortes, an AT&T Eminent Scholar in the Department of Electrical and Computer Engineering and director of the ACIS Lab. Fortes estimates 15 to 20 times more space will be needed long-term, along with a commitment to upgrad-

ing the equipment. Redundancy, too, is built in to safeguard the data from catastrophes that could wipe out the database. Perhaps the biggest commitment — and biggest opportunity — lies in hosting the data, Fortes says.

“The greatest asset in the information age is data, and that’s something that should be the responsibility of an institution of knowledge, like a university. Hosting this data could be a differentiator from one university to the other,” Fortes says.

The point of iDigBio is to have the data forever as a resource to do bigger and better things, to enable scientists to answer questions that cannot now be answered.

“If you are in a position to do that you clearly have a competitive advantage,” Fortes says.

“Just like having an excellent library is a differentiator, so is data,”

Fortes says. “If we do it right everyone will come to us. They may not come by walking, they may come through the Internet, but that will enable other things to happen and that will pay for the long-term commitment to host the data.”

As rewarding as it is to expand access beyond the traditional realm of museum collections, Soltis also is excited about the novel ways the data can be studied. By using label data — where and when a specimen was collected — locations can be plotted as GPS coordinates to construct models of species distribution based on variables such as temperature or rainfall.

That is a much more powerful way of understanding the range of a species, Soltis says.

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The UF Museum has some of the most comprehensive and widely utilized collections in the world.

Most of the museum’s collections rank among the top 10 nationally and internationally.

Archaeology Caribbean Archaeology Ceramic Technology Laboratory Environmental Archaeology (Zooarchaeology, Archaeobotany & Archaeopedology) Florida Archaeology Historical Archaeology Latin American Archaeology South Florida Archaeology Ethnography Latin American Ethnography North American Ethnography Natural Sciences Botany/Herbarium (Plants) Herpetology (Reptiles & Amphibians) Ichthyology (Fishes) Genetic Resources Repository Lepidoptera (Butterflies & Moths) Mammalogy Molecular Systematics & Evolutionary Genetics Malacology & Invertebrate Zoology (Mollusks & Marine Invertebrates) Ornithology (Birds) Paleontology Invertebrate Paleontology (Invertebrate Fossils) Paleobotany & Palynology (Fossil Plants & Pollen) Vertebrate Paleontology (Vertebrate Fossils)

Recently Soltis and colleagues used the digital label data that exist for about half of Florida’s 4,000 species of plants to construct a model of the effects of climate change on plant communities in Florida.

Based on herbarium records, Soltis and her colleagues plotted each species on a map, then combined the maps to create a picture of plant species diversity in Florida today.

Then, using the characteristics that determine the niche of each species — for example, temperature, rainfall, soil type — the group looked at predictions for those attributes in future climate change scenarios. Her model for 2050 shows an alteration in species distribution as some areas dry out and others become wetter, with an overall loss of plant diversity in Florida, creating challenges for conservation (see map).

“This sort of analysis wouldn’t be possible at all if we didn’t have the digitized data from the museum specimens,” Soltis says. “We can use the digitized information to find links between evolutionary history, response to climate change and extinction risk.”

Soltis points out that her species diversity model was incredibly complicated even though it was only in

Museum collections are varied and plentiful, from pinning boxes used for butterfly specimens to jars of fishes and rows of shelves holding mammal bones.

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Florida and only half of the plant species. Translating it to a larger scale, regionally or nationally, with many more data points makes it a huge data problem because it involves heterogeneous data: distributions, evolutionary history, possibly genetics. There is talk already of linking iDigBio with GenBank, the national genetic sequence database, creating yet another avenue of inquiry.

“The possibilities of linking all these together present a whole new range of opportunities,” Soltis said.

“There are almost no precedents for being able to do that. Big data takes on a unique shape when we think about biodiversity.”

Big data projects like iDigBio are changing the past emphasis in science on hypothesis testing, Soltis says.

Sometimes a scientist might not know what to hypothesize, but patterns can emerge from the data and point to a hypothesis to test.

“Without access to the data, you might not even know to ask the question, so I think this whole concept of data-driven science is a really important paradigm shift for us,” Soltis says, “and I think our biodiversity data are perfect for exploring the bounds of that.”

“Most species discoveries are actually made in museums, not in the wild, anymore.”

PRESENT

Pam Soltis

Research director for iDigBio

2050

Page says iDigBio is not only a big data issue, it’s a dark data issue, too, because so much of the data has been hidden from view.

“This is a clear example of bringing the data out of the darkness and into the light,” Page says.

The process of shedding light has won over the few institutions that were lukewarm about joining the digitization effort, Page says. Getting funding for collections work sometimes is difficult. It’s a challenge to convince administrators that a “bunch of dead fish in jars has any value,” but as more data go online, museums will have an easier time demonstrating the value of their collections.

He says he laughs when people ask what scientists are going to do with all these data. iDigBio, he says, is much more than an exercise in knowledge for the sake of knowledge. The data will be central to exploring climate change, populations, evolution,

extinction, conservation, the number of species that share the planet with us, the very history of life on Earth.

These are huge research questions, so huge that they have been intractable, Page says, until now.

“I really prefer to just work with fish, but I’m more and more excited about this,” Page says. “The aha! moments, I think, will be happening all the time.”

Larry Page Curator of Fishes lpage@flmnh.ufl.edu José A.B. Fortes Professor of Electrical and Computer Engineering and Computer Science fortes@ufl.edu Pamela Soltis Curator of Molecular Systematics & Evolutionary Genetics psoltis@flmnh.ufl.edu Related website: https://www.idigbio.org/

Each of the specimen jar icons throughout this story represents 100 jars in the fish collection at the Florida Museum of Natural History.

Ichthyology is just one of many collections at UF’s museum, and UF’s museum is just one of hundreds around the country, where an estimated 1 billion biological specimens are tucked away.

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24 Summer 2014

Metabolites

map biological processes in all living things

BY CLAIRE BARALT

Every

process that happens in our bodies leaves a trail of small molecules called metabolites.

A cancer cell starts dividing uncontrollably, it leaves a trail. An athlete injects steroids to improve performance, it leaves a trail. A stroke cuts off blood to a portion of the brain, it leaves a trail.

But until recently the trails were so faint that scientists couldn’t see them.

Now, through the use of increasingly powerful mass spectrometry and nuclear magnetic resonance, the telltale signs of countless processes occurring in our bodies are being revealed.

“By measuring metabolites, we can get a unique window into health and disease. Metabolites keep everything going. They convert food into energy.

They allow cells, tissues and organs to communicate. They’re the starting materials for DNA, proteins and cell membranes,” says Arthur S. Edison, a professor of biochemistry and molecular biology in the UF College of Medicine.

There are many twists and turns on the road between our DNA and our observable traits — from hair color to cancer tumor. Metabolites offer clues to what’s occurring along the way.

By identifying which metabolites are present and at what concentration, the emerging science of metabolomics offers a new lens through which scientists can assess and understand the state of nutrition, infection, health or disease in an organism, whether human, animal, plant or microbe.

Humans are estimated to have thousands of metabolites, but scientists are still at the early stage of identifying and being able to consistently measure them.

The University of Florida is home to one of six centers funded by the National Institutes of Health to spur advances in metabolomics. In 2013, UF launched its Southeast Center for Integrated Metabolomics with a fiveyear, $9 million NIH grant.

The quest for metabolites typically involves either searching for

Photography by John Jernigan; Illustration by KD Kinsley-Momberger

specific compounds, known as targeted metabolomics, or cataloging all compounds in a sample, called global metabolomics. Databases of identified metabolites are emerging and expanding around the world. Scientists use these databases like nature enthusiasts use field guides, with the hope of finding a match or discovering a new metabolite among their data.

The UF center has four closely integrated technical cores that develop and provide services bridging the two technologies most commonly used to generate metabolomics data: mass spectrometry and nuclear magnetic resonance.

“Our biggest strength is that we really pulled together the major technologies in a significant way,” Edison says. “Many groups use one technology or the other. We’re going to find better ways to use technologies together.”

Edison jointly leads the UF center with Richard A. Yost, a professor and head of analytical chemistry in the UF College of Liberal Arts and Sciences.

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“

By measuring metabolites, we can get a unique window into health and disease.

”

—ARTHUR EDISON

The new center is part of the UF Clinical and Translational Science Institute, which over the last five years has supported the development of biomedical mass spectrometry at UF. When the NIH funding announcement presented an opportunity to integrate and expand metabolomics resources across UF and with external partners, the CTSI provided resources and infrastructure to help create the new center. The center’s partners include Sanford-Burnham Medical Research Institute at Lake Nona, the

26 Summer 2014

National High Magnetic Field Laboratory, Ohio State University, the University of Georgia, Imperial College London, the University of Geneva and industry partners IROA Technologies and Thermo Fisher Scientific.

Weighing In

Metabolites are identified based on their molecular weight. Mass spectrometry is highly sensitive and can detect minute quantities of such compounds.

The process starts with a biological sample — typically urine or blood. The sample is run through a mass spectrometer, which separates the sample into its chemical constituents by giving an electric charge to each component.

The components then travel different paths through the device so they can be precisely identified and their molecular weight reported.

The UF center provides mass spectrometry services in collaboration with

Sanford-Burnham, which specializes in targeted metabolomics. UF offers complementary expertise in global metabolomics.

“Metabolites are numerous and remarkably diverse in terms of their structures. They display different sizes, polarities, and other properties. We have technology platforms that allow us to generate a broad and comprehensive profile of a vast number of unique metabolites,” says Stephen Gardell, senior director of scientific resources and an associate professor at SanfordBurnham. Gardell leads the center’s mass spectrometry services with Timothy Garrett, a research assistant professor of pathology, immunology and laboratory sciences in the UF College of Medicine.

One of the challenges for traditional mass spectrometry is that it relies solely on molecular weight to identify the metabolites it detects. The heavier a metabolite is, the more molecular

compounds there are that could yield a particular weight.

Imagine trying to guess what’s inside a package based only on its weight, but without being able to see its shape or size, or sense what happens when you shake it. That’s where nuclear magnetic resonance comes in.

Using NMR is like x-raying the package to see what’s inside — which, in the case of a metabolite, is atoms. To identify atoms and their location in complex molecules, NMR tracks the spinning of atomic nuclei in response to magnetic fields.

NMR is not as sensitive as mass spectrometry. While mass spectrometry can measure thousands of features, NMR can measure hundreds.

The strength of NMR is that it generates separate peaks for every atom type in the molecule, which makes identification of the molecule more straightforward.

“If you have an unknown chemical that doesn’t match any of the databases, you almost always need NMR to get the real atom connectivity. It’s close to impossible to get the identity of a new compound with just mass spectrometry. NMR and mass spectrometry together are an important part of the identification of unknown biomarkers,” Edison says.

Not content to make do with the limitations of current technologies, Edison’s research group is pioneering the development and use of some of the world’s most sensitive NMR probes.

Edison leads the center’s NMR services with Glenn Walter, an associate professor of physiology and functional genomics in the UF College of Medicine. The NMR core’s facilities

Glenn Walter Timothy Garrett

hum with activity. Shakers the size of tanning beds jostle their incubating inhabitants: worm-like nematodes that serve as model organisms for metabolomics experiments. Edison and his team migrate among computers, freezers and robots. Ladders lead to the top of two stately magnets processing samples in the National High Magnetic Field Laboratory’s Advanced Magnetic Resonance Imaging and Spectroscopy Facility at UF.

Data Mining

The use of different technologies adds to the complexity of metabolomics data. The center’s bioinformatics core helps ensure high-quality, standardized data — regardless of the technology used — along with a robust set of tools researchers can use to analyze their data.

The bioinformatics core is led

by Lauren McIntyre, a professor of molecular genetics and microbiology in the UF College of Medicine. The core is developing the workflows, infrastructure and automation that will enable the center to process thousands of samples from researchers.

Lauren McIntyre

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“

We have computer scientists and engineers who think about big data, scientists who create instruments that make big data, and physicians who use that data to answer biomedical questions.

”

— RICK YOST

28 Summer 2014

“When we’re doing it well, it will be almost invisible to everybody,” McIntyre says.

But data generated by the UF center does not all stay at UF. A central tenet of the NIH consortium is that all metabolomics data generated by the six centers with NIH support will be deposited in a national data repository and coordinating center, which is housed at the University of California, San Diego. The data center is led by Shankar Subramaniam, a professor of bioengineering at UCSD. Subramaniam outlines five challenges to working with big data that are relevant to biology and his center’s work with the metabolomics consortium — organizing the data; developing standard ways of naming the data; integrating the data; making sense of the data once it’s integrated; and ultimately using the data to determine causality.

Making sense of the data involves looking for patterns. “With patterns

in biology — it’s not like looking for a needle in a haystack. It’s like searching for hay in a haystack. The whole area of data mining and statistical learning from data becomes very important,” Subramaniam says.

At the UF center, McIntyre’s bioinformatics core will help tackle such challenges. She is developing new methods for integrating and modeling metabolomics data, as well as integrating metabolomics data with other “omics” data.

Metabolomics produces big data, but not on the scale generated by Wal-Mart or Wall Street. Integration with other “omics” such as genomics, proteomics and transcriptomics will be necessary before scientists can relate metabolites to changes in genes, proteins and the regulation of cell behavior, and that will cause the data sets to grow dramatically.

“One of the advantages we have at UF — it’s a very interdisciplinary and diverse place,” Yost says. “We have

computer scientists and engineers who think about big data, scientists who create instruments that make big data, and physicians who use that data to answer biomedical questions.”

Erik Deumens is one of those computer scientists. Deumens directs UF Research Computing, which serves the UF metabolomics center’s data processing and storage needs. Resources such as UF’s HiPerGator supercomputer and the Internet2 high-speed network connection make it possible for UF researchers to collaborate and compete in the big-data arena.

“The Southeast Center for Integrated Metabolomics is bringing together different aspects of people’s metabolism and all kinds of information about health and biochemistry processes. You gather all the data, put it one place and have a chance to look at it from a new point of view. We’re the enabler of that next step,” Deumens says.

Noise Filters

Innovation in data generation is a hallmark of the center at UF. “Metabolomics is the ultimate healthcare platform, but it won’t be useful to anyone until you get the time it takes to do it and the time to understand what it’s telling you down to something reasonable. That’s what the NIH centers are going to do,” says Chris Beecher, founder and chief scientific officer of IROA Technologies, one of the UF center’s partners.

Beecher is developing a technique that is transforming how metabolomics data are generated. Called isotopic ratio outlier analysis, or IROA, it tags all molecules that come from a living system prior to running samples through a mass spectrometer. Those tags allow scientists to identify all of the signals

from the living system and ignore all of the other “noise,” or signals from nonliving systems that result from the mass spectrometry process — a major hurdle in metabolomics.

Innovation is similarly thriving in the UF center’s advanced mass spectrometry core led by Yost. Even amid a spring break void of students, traces of his research group’s creative spirit abound. On Yost’s table, a bobblehead of Nobel Prize-winning physicist Wolfgang Paul knowingly nods next to a specimen of Paul’s handiwork: a quadrupole mass analyzer, four rods neatly bound together.

As it turns out, Yost spent a great deal of time tinkering with the quadrupole as a graduate student at Michigan State University. Together with his advisor Chris Enke, he conceived of the computerized tandem quadrupole mass spectrometer. Scientific reviewers for the National Science Foundation did not believe it would work, but the Office of Naval Research was willing to chance that it might. And that chance paid off. Today it is the most common mass spectrometer in the world, with sales of nearly $1 billion each year.

“Oftentimes when you’re deep in a discipline, there are things you know that are facts, and there are things you think you know that are folklore. And oftentimes the folklore keeps you from moving forward in innovative ways,” Yost says.

Yost’s lab is devoted to pushing past the folklore to cultivate instrumentation breakthroughs. His team is now focused on advancing imaging mass spectrometry for tissues. Instead of applying mass spectrometry to the usual urine or blood samples, this technique applies mass spectrometry methods across a section of tissue. The

idea is that the spatial relationships between metabolites could convey a lot of information with respect to what’s happening in an organ, for example. Processing a blood sample can reveal how much glucose or lactate is present in the blood, but it doesn’t indicate what those levels are in the liver or heart or brain.

Over time, as these new technologies and methodologies are developed, tested and refined, they will become part of the UF center’s service offerings for investigators. The center also offers training and pilot funding to help scientists access and use its services.

A strong demand for metabolomics already is emerging. In its first six months, the center received close to 100 inquiries from investigators at nearly 30 institutions. Investigators are coming to the center with a range of questions for which they hope metabolomics might yield clues. Projects in discussion are diverse and stimulating.

They include looking at the effects of stress during pregnancy on a mother and her fetus; metabolomics approaches to drug discovery in microbes; studies of the physiology of human pathogens; and studies of metabolic disease in humans and animals.

“We’re at this ‘wild west’ stage of trying to figure it out. I’m confident this consortium will point the field in a better direction in five years. Everything won’t be solved, but it will be much clearer what you can do and the importance of it,” Edison says.

Arthur S. Edison Professor of Biochemistry and Molecular Biology aedison@ufl.edu Richard A. Yost Professor of Chemistry ryost@chem.ufl.edu Related website: http://secim.ufl.edu/

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Craig Mahaffey

Juan Gilbert

HUMAN-CENTERED COMPUTING BONANZA COLLEGE OF ENGINEERING RECRUITS NATIONAL LEADERS IN EMERGING USER-FRIENDLY FIELD

T

he University of Florida has recruited a team of computer scientists with specialties in what’s known as human-centered computing to help it become a national leader in making computers more secure and more personalized to individual needs.

Four faculty members, recruited from the same department at Clemson University, are joining the College of Engineering’s Department of Computer and Information Science and Engineering, known as CISE. This

30 Summer 2014

“cluster” hire fits into strategies at the college and university levels to expand research into several key areas over the next year.

“As our relationship with technology becomes more pervasive, comfortable interfaces between humans and computers become more important,” said CISE department Chair Paul Gader. “Human-centered computing is the frontier where computers begin to recognize what makes each of us unique, and then adapt to offer each of us a more personalized experience.

Bringing this team on board will make UF a leader in ensuring greater accessibility for all human-computer interactions.”

The team arrives with a variety of research interests: • Juan Gilbert and his team gained national recognition when they developed the technology to make voting more accessible and secure. His electronic voting interface has created a new standard for universal accessibility in elections. Gilbert will be the Andrew Banks Family Preeminence Endowed Chair at UF. • Damon Woodard is an expert in biometrics, or identity technology. His work with the U.S. intelligence community includes periocular-based and tightly coupled face/iris recognition systems. The main focus of his current work is the development of techniques that allow machines to establish an individual’s identity even when using lower quality or incomplete data.

• Kyla McMullen specializes in virtual spatial audio, which allows a listener to hear a sound over headphones as though it were coming from a specific point in their immediate environment. She is interested in using this rendering to create more immersive virtual environments, develop assistive technology for persons with visual impairments, and to sonify trends in Big Data.

• Christina Gardner-McCune is a computer science education researcher.

She develops interest- and disciplinebased computing curriculum and after-school and summer camp

programming to encourage K-12 students to enter STEM-related careers.

She currently serves on the College Board’s development committee for the new Advanced Placement Computer Science Principles Exam.

The team brings millions of dollars in federal grants to UF and more than a dozen doctoral students. They will be joining CISE’s growing HCC team, which includes Benjamin Lok — who developed the technology behind local adaptive learning startup Shadow Health — and Lisa Anthony and Eakta Jain, both recent doctoral graduates from Carnegie Mellon University who came to UF this year.

“If your quality of life has been enhanced by a technology, humancentered computing is probably the reason,” said College of Engineering Dean Cammy Abernathy. “This team has an excellent reputation for their revolutionary research, their collaboration across disciplines, and their wide focus that includes the needs of all members of society. Their addition positions us to have a new center of excellence. We are thrilled to have them.”

“In addition to this team, CISE is hiring new faculty in areas of Big Data, cyber security, and social networks,” Gader said. “Our mission in the department is to improve quality of life and we’re definitely headed in the right direction.”

Juan Gilbert demonstrates an electronic voting system to South Carolina Congressman James Clyburn.

Doctoral student Chris Crawford demonstrates programming to middle school students.

Doctoral student Naja Mack demonstrates an electronic voting system at the Capitol in Washington.

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To gain a better understanding of why dementia is more common among people with Parkinson’s disease, UF researchers are using MRI images like this to compare the brain tissue of Parkinson’s patients with different types of cognitive difficulties. Clinical and health psychology Associate Professor Catherine Price says the research — funded by a $2.1 million National Institutes of Health grant — may enable researchers to “foreshadow the type of impairment, if any, patients will have down the road.”