Thursday, December 20, 2007

Knockout mice program established at UA

Gene targeting revolutionized the way scientists use mice to study the function of genes. Also called “knockout” technology, the technique allows scientists to create animal models of human disease. After the decoding of the mouse and human genomes in the early part of this decade unearthed thousands of new genes of unknown function, knockout mice became a prime source of information for making sense of them. Most human genes can be studied by looking at mouse genes because the protein-encoding genes of both are 85 percent identical in sequence.

Scientists have developed hundreds of mouse models of human ailments, including heart disease, diabetes, degenerative brain disorders and cancer. The three scientists who developed this technique won the Nobel Prize in Medicine this year. BIO5 member Tom Doetschman, PhD, a professor in the College of Medicine at The University of Arizona (UA), played an active role in the mid 1980s in the lab of one of those winners, Oliver Smithies, PhD, of the University of North Carolina Chapel Hill. While in Dr. Smithies' laboratory, Dr. Doetschman published two papers that played a significant role in the award.

(See http://nobelprize.org/nobel_prizes/medicine/laureates/2007/adv.html for further details on the award.)

Dr. Doetschman arrived at the UA in early 2006 from the University of Cinncinati, bringing with him his research program and a reknowned genetically engineering mouse model program. Two years ago, the National Institutes of Health (NIH) began funding the “knockout” of every gene in the mouse genome – all 30,000 of them. Dr. Doetschman’s lab in Cinncinati was responsible for knocking out 300 of them before he relocated to Arizona where he is continuing with that work as a service to all University researchers.

“Since the time of Mendel, we have studied what goes wrong when a gene is mutated. The beauty of the mouse as an experimental organism is that we can mutate a specific gene in a pre-planned way and then learn the consequences of that alteration at the whole animal level in a mammal with considerable genetic similarity. As a result, we can understand the function of the gene and why specific genetic mutations can cause human disease,” says Dr. Doetschman, who has a doctorate in biochemistry and biophysics from the University of Connecticut and completed three postdoctoral fellowships before establishing his lab at the University of Cincinnati.

Mayo Clinic study shows potential for new drug treatment for multiple myeloma

[Source: Mayo Clinic] - Mayo Clinic researchers today presented results of a phase II trial that shows potential to help patients with multiple myeloma, an incurable cancer of the white blood cells affecting more than 50,000 patients in the U.S.

“For newly-diagnosed multiple myeloma patients, this new drug treatment provides a more frequent, rapid and deep response, compared with earlier treatment options,” said Craig B. Reeder, M.D., a Mayo Clinic hematologist/oncologist and lead investigator of the study. “This is the first time we have studied this treatment in newly-diagnosed patients with this condition. This new treatment proved to be very successful.”

The research team studied 30 patients enrolled in the trial who were administered a drug regimen using cyclophosphamide, bortezomib and dexamethasone (Cybor-D). That combination showed an improved response over the drug therapy used historically – lenalidomide-dexamethasone (L-Dex).

The 30 trial patients were administered Cybor-D. A control group of 34 patients was treated with L-Dex. Findings reveal that Cybor-D produced a higher rate of good or complete responses than the L-Dex.

Cybor-D was found to produce a rapid initial decline and reduction in M protein, an antibody protein that can build up in the bone marrow and cause the blood to thicken or damage the kidneys.

Other Mayo Clinic researchers contributing to the study included Rafael Fonseca, M.D.; Leif Bergsagel, M.D.; S. Vincent Rajkumar, M.D.; Jacy Boesiger; Christine Chen; Martha Lacy, M.D.; Keith Stewart, M.B.Ch.B.; Joseph Hentz and Nicholas Pirooz. Researchers from Princess Margaret Hospital in Toronto, Ontario, also contributed to the study.

Findings were reported by Dr. Reeder at the American Society of Hematology’s annual meeting in Atlanta Dec. 8-11, 2007.

$6M UA fund for diseases of joints

[Source: Eric Swedlund, Arizona Daily Star] - The University of Arizona has created a new endowed faculty position and research fund for the study of rheumatology, funded by a $6 million bequest from a longtime Tucson doctor.

Dr. Salvatore Albani was appointed Monday as the Charles A.L. and Suzanne M. Stephens Chair of Rheumatology. Albani, who begins next month, will also serve as the director of the Arizona Arthritis Center.

Dr. Charles Stephens and his wife Suzanne left their entire estate to fund rheumatology research at the College of Medicine. Dr. Stephens was a captain in the U.S. Army, working in rheumatology and treating concentration camp survivors at the end of World War II. After leaving the army as a major in 1946, he joined the Holbrook-Hill Medical Clinic in Tucson.

Stephens was also an early faculty member in the UA's medical school and worked with the Arthritis & Rheumatism Foundation and Southwest Clinic and Research Institute, early organizations that helped develop the Arthritis Foundation and Arizona Arthritis Center. Dr. Stephens died in 2002, and his wife passed away in 2004.

Albani comes to the UA from the University of California at San Diego, where he was a professor of medicine and pediatrics and director of the Translational Research Unit of the school's Clinical Investigation Institute. Born in Italy, Albani joined the University of California at San Diego in 1993.

Local investor group aims to market UA tech ideas

[Source: Jack Gillum, ARIZONA DAILY STAR] - If Alicia Reeves and Olin Feuerbacher have their way, testing time for dangerous E. coli bacteria would be cut to a fraction of what it takes now.

The duo hope to move that vision closer to reality with backing from a new group of local investors created to help bring University of Arizona technologies to market.

Reeves' and Feuerbacher's company, Innovis Technologies, is developing its E. coli test based on research performed at the UA. It was one of three biotech groups that presented their technologies on Oct. 8 at the inaugural meeting of Desert Tech Investors LLC.

Desert Tech, which has about 45 members, has entered into an alliance with the UA via the Arizona Enterprise Program. The UA's Office of Technology Transfer is working with Desert Tech to invest $400,000 in research on UA innovations with "high commercial potential," the UA said.

The group's president, Jerry Sonenblick, and its executive vice president, Bob Morrison, are members of the Desert Angels. That local group is made up of so-called "angel" investors — people with a qualifying level of wealth who invest individually in startup companies — although the two groups are not connected.

The Desert Tech program "is a rare, and very possibly unique, mechanism for a university to formally match the interests and expertise of local angel investors with those of a university and its individual researchers," said Stephen ONeil of the Technology Transfer Office. The university and the investor group will work "transparently within university policies regarding intellectual property and conflict of interest," he said.

Such a public-private partnership can combine investors with the "educational, technical knowledge" of professors to encourage successful biotech companies, Sonenblick said.

"When the light bulb goes off in a university professor's head," Sonenblick said, Desert Tech "will have the first look at contributing capital, person power and mentoring advice toward achieving proof of concept."

"This is the embryo stage of technological development," he said.

Innovis, like the other ideas showcased, is at that formative stage, and its technology is timely. The process of detecting E. coli — which can cause potentially fatal illness and has been blamed for sickness and millions of dollars in product losses recently — can take 24 to 48 hours.

But if Innovis' product is successful, companies can sniff out trouble in as little as 10 minutes.

The Innovis idea, developed by UA chemist Dr. Indraneel Ghosh, uses a technology known as sequence enabled reassembly to detect E. coli at the DNA level using specialized zinc "fingerprints." Reeves and Feuerbacher worked together at the UA through the McGuire Entrepreneurship Program.

It would be "as easy as reading a color pregnancy test," Feuerbacher, Innovis' chief scientific officer, said during a recent demonstration.

Other projects presented at Desert Tech's first meeting include:

● A simple defibrillator, or electrical heart stimulator, that uses AC power and would be cheaper to manufacture than existing over-the-counter models. Project head Dr. M. Reza Movahed, a UA cardiologist, said current automatic external defibrillators are costly to make because of their specialized lithium batteries.

● Nasser Peyghambarian, a professor in the UA College of Optical Sciences who already has commercialized several products, plans to develop a new kind of low-power, fiber-optic laser.

Desert Tech plans to meet next on Nov. 28, when the group will vote on whether to proceed with one of the companies that gave a presentation in October, as well as another that will present in November.

Deadline nears for SFAz's Competitive Advantage Award program

The proposal deadline for the Competitive Advantage Award (CAA) program of Science Foundation Arizona is January 16. Grants will support investigators in Arizona research-performing institutions in three areas: sustainability, information and communication technologies, and biosciences. CAA awards are intended to lead to more federal, foundation, and industrial investments in Arizona research and researchers. The program's Request for Proposals is accessible here.

Biodiversity Informatics Initiative Underway

[Source: Bio5] - Two recently recruited scientists from UC Davis, Michael Sanderson, PhD, and Michelle McMahon, PhD, are jump-starting the new Biodiversity Informatics initiative at The University of Arizona (UA).

The initiative is building on existing UA strengths in biology and informatics. As it develops, the initiative will 1) provide nationally unique research and training programs, 2) establish a framework for meeting the expanding bioinformatics needs at the UA, and 3) complement the informatics programs at other institutions in the State. Funding for the initiative comes from the UA BIO5 Institute, College of Science and College of Agriculture and Life Sciences.

Dr. Sanderson, a professor in the Department of Ecology and Evolutionary Biology (EEB) and a BIO5 member, is spearheading the development of the research and training program, focusing on the Sonoran Desert. Dr. McMahon, a research assistant professor in the Department of Plant Sciences, runs the UA Herbarium.

With more than 380,000 specimens, it is the largest herbarium in the arid southwest and unique in having the largest collection in the world of plants from Arizona and Sonora, Mexico. It is one of several outstanding UA natural history collections.Plans also include competitively funded pilot projects to stimulate interactions between UA information scientists and biological researchers, and establishing a graduate interdisciplinary training program. For example, EEB is hiring postdoctoral level curators that will begin this fall; the new positions are part of a renewed investment in the UA natural history collections.

“The new curator positions are exciting because they will bring in people who are interested in combining rich resources in natural history collections with modern technology and cutting edge scientific questions,” says Dr. McMahon.

Why Informatics?

One common theme across all scientific activities and operations that support biological research and medical care is the need to share data efficiently and effectively. Yet, the data are not often in a form that is suitable for straightforward storage and application using simple data analysis tools such as statistical methods, data mining approaches or visualization. Some of these data are too voluminous to easily comprehend and manipulate unless presented in clustered, visual and other forms (e.g. image data that are digitized for analysis are often too complex to effectively analyze).

Advanced technology is required for the management of this scientific knowledge; thus it is imperative that biologists collecting and interpreting these data are interfacing with information technologists working at the cutting-edge of knowledge management.

What is Biodiversity Informatics?

Distinguished from typical “bioinformatics”, which emphasizes depth in genomic and post-genomic information mainly in model organisms and humans, “biodiversity informatics” focuses on breadth—attributes of large collections of disparate species at scales ranging from populations to geographic regions to entire biotas, and ultimately the entire phylogenetic tree of life. Biodiversity informatics uses the power of computational and information technologies to organize and analyze biological data from research collections, experiments, remote sensing, modeling, database searches and instrumentation – to deliver answers to users throughout the world. Today, the Internet and World Wide Web are powerful tools for linking and utilizing the extraordinary assets of natural history institutions.

Banner teams with international health care giant on Alzheimer's research

[Source: Phoenix Business Journal] - The Banner Alzheimer's Institute of Phoenix and AstraZeneca, a multi-billion-dollar international health care company, hope to advance understanding and treatment of Alzheimer's disease.

Scientists at the Banner Alzheimer's Institute and AstraZeneca plan to use cutting-edge brain imaging methods to find clues to how the disease progresses and affects the brain, offering a baseline for future studies. The information potentially could be used to monitor the effectiveness of existing treatments, reveal new therapeutic targets and enhance understanding of ways to curtail disease progression, the two groups said in a statement Wednesday.

Alzheimer's is the most common form of dementia and affects more than 5 million Americans.
"We look forward to working with AstraZeneca on the development of this promising research tool for the early detection, tracking and scientific study of Alzheimer's disease in the living human brain," said Dr. Eric Reiman, executive director of the Banner Alzheimer's Institute, in a statement. "Our goals are to advance the scientific understanding of Alzheimer's disease and evaluate promising disease-slowing and prevention therapies in the most rapid and rigorous way."

Tuesday, December 18, 2007

Tool developed at UA may spot cancer faster

[Source: Alan Fischer, Tucson Citizen] - Cancer and other illnesses could be detected - and treated - years sooner, thanks to a tool developed by a Tucson company spun off from University of Arizona research. "This technology can save lives," said Mary J. Wirth. "You want to detect it before it has metastasized."

BioVidria Inc., spun off from Wirth's work at UA, will offer tools to detect tiny cancers and other diseases that current diagnostic methods miss and do the job more quickly, said Wirth, the company's president and a UA professor of chemistry. Early detection of cancer using bioVidria's products - even long before symptoms appear - will allow doctors to offer more effective treatments. "We want to make it so you go from rarely curable to always curable," Wirth said.

The company in early January will begin prototype manufacturing of BrightSlides, testing slides that are 80 times more sensitive in detecting cancer and other diseases than the slides now used with DNA in labs around the world, Wirth said. BrightSlides is a new development in the $1 billion-per-year DNA microarray market, said Wirth, a member of UA's BIO5 Institute. Microarray is a technology that studies genes to understand how they work and what role they play in the development of cancer and other diseases. "We already have companies asking us for prototypes," Wirth said.

Cancer screening starts by printing a glass slide with single strands of DNA or proteins, using a device like a tiny automated quill pen. Each 1-by-3-inch microarray slide can contain more than 20,000 human genes. BioVidria's secret is glazing a 10-micron-thick layer of silica colloidal crystals onto a conventional lab slide. The coating is one-fifth the thickness of a human hair. "Silica colloidal crystals are the same as opals," she said. "We're making artificial opals and depositing them on the slide."

That allows researchers to see potential problems with 80 times greater brightness, or sensitivity, she said. "We could use smaller sample amounts. With this we can find the needle in the haystack," said George S. Watts, co-director of UA's Genomics Shared Service and a researcher at the Arizona Cancer Center who works with microarrays. "This could offer more reliable results," Watts said. "Thousands of labs around the world would benefit around it, and thousands of research projects ranging from improving the quality of rice crops to better cancer diagnosis would benefit."

The clear coating, which is like adding numerous layers of pool balls to a flat surface, gives the slide more contact area with the specimen being tested, said John L. Lemon, a UA chemistry doctoral candidate and intern with bioVidria. BioVidria has other technologies that will aid cancer researchers and doctors. The company's coated slides will make the process of discovering the protein biomarkers linked with cancer faster. Researchers today use a tile-size polyacrylamide gel material when separating out proteins to determine difference between healthy and cancerous cells, Wirth said.
By using smaller, stamp-sized coated glass slides, the time needed for the separation process can be cut from two days to minutes, she said. Eventually, bioVidria's products could be used to develop a simple blood test to screen for cancers and to develop better therapeutics to treat the disease, she said.

Wirth was inspired to launch her research after seeing a paper in an optics journal on how silica colloidal crystals were used successfully in photonics. Photonics is the study and technology of using light for transmitting information. "I looked at the materials being used and realized they could be used for microarrays," she said.

Patents have been applied for on bioVidria's technology, which is owned by the Arizona Board of Regents. The state will receive financial benefits when the products go commercial, Wirth said. The company was incorporated in July. Tomika R.C. Velarde, who received her graduate degree in chemistry from UA while working in Wirth's lab, will begin manufacturing and testing BrightSlides in early January. "I'm excited to be applying research done for my master's to real-life science," Velarde said. "This will allow people to do experiments they would not have been able to do with what's available now."

The company is self-funded for now, but that is expected to change with growth. A presentation Dec. 5 at an event showcasing the UA Professional Science Master's Program in Applied Science and Business, a program in which Lemon is a participant, resulted in contact with potential financial backers. The program offers scientists guidance in areas such as developing funding pitches and writing business plans for commercializing their lab work, Lemon said. Wirth and Watts have applied for a Small Business Technology Transfer grant from the National Institutes of Health to fund large-scale testing of BrightSlides on UA's highest output microarray printer, which deposits thousands of tiny spots of DNA and proteins on the slides.

How it works

  • Microarray is a technology that studies genes to understand how they work and what role they play in the development of cancer and other diseases.
  • Proteomics analyzes proteins and signaling processes initiated by our genes.
  • Cancer screening starts by printing a glass slide with single strands of DNA or proteins, using a device like a tiny automated quill pen.
  • Each 1-by-3-inch microarray slide can contain more than 20,000 human genes.
  • Components of human cells extracted from a biopsy sample being tested are added to the slides and are attracted to a spot on the slide that reveals their identity or gene expression.
  • Researchers examining the results can find genetic materials that are not present in a healthy sample and that can be a marker for the presence of cancer or other diseases such as diabetes, heart disease, obesity, Alzheimer's disease and infectious diseases such as severe acute respiratory syndrome (SARS), influenza, pneumonia, methicillin-resistant Staphylococcus aureus (MRSA) and valley fever.

Monday, December 17, 2007

ASU paves way for bioscience education

[Source: ASU News] - To help meet the need of Arizona’s booming bioscience sector and create the next generation of highly skilled, interdisciplinary scientists, the Arizona Board of Regents recently approved an innovative ASU graduate degree in biological design.

The biological design doctoral program seeks to attract and train new scientific talent to use an outcome-driven, interdisciplinary approach in solving major global challenges in human health and the environment. The program is a collaboration between ASU’s Biodesign Institute, the Ira A. Fulton School of Engineering, and the College of Liberal Arts and Sciences.

“The challenges for the next generation of scientists are more complex and inter-related than ever before,” explains Biodesign Institute researcher Neal Woodbury, who directs the institute’s Center for BioOptical Nanotechnology and is a professor in the College of Liberal Arts and Sciences. “Problems as seemingly unrelated as global pandemics, the need for better medical diagnostics and environmental deterioration all stand to benefit from a convergence of technologies from multiple fields of science. Our goal is to teach students to work in interdisciplinary teams that focus on solving a large-scale problem, rather than working independently on an isolated piece of that problem, which is the more traditional approach.”
The new program reflects ASU’s commitment to “use-inspired” research, one of seven imperatives outlined in 2002 by ASU President Michael Crow as part of the university’s 10-year strategic plan.

An executive committee including individuals from across ASU’s bioscience, engineering, informatics and mathematics academic units spearheaded the effort to create the new doctoral program.

According to electrical engineering professor Trevor Thornton, a member of the biological design doctoral graduate program’s executive committee, the main challenge was designing a curriculum to meet the mission of multidisciplinary, solution-driven research.

“An undergraduate curriculum allows a student to gain mastery of an individual discipline,” Thornton says. “The biological design Ph.D. program will allow students to apply their core expertise to multidisciplinary projects while providing them with the skills they need to work with scientists and engineers from other disciplines.”

The doctoral program consists of a two-semester core course sequence to provide training in bio-related areas. There, doctoral candidates will receive intensive training in all the relevant biology-related areas (including biophysics, biomedical engineering, biochemistry and molecular biology) combined with emergent disciplines, including synthetic biology, systems biology, artificial tissues and drug development.

More than 100 ASU participating faculty will be eligible to mentor students in the program. Initially, 15 students will be recruited each year, generating a total student enrollment of around 60 students by the fourth year.

Science is in the midst of a profound transformation, with increasingly complex data sets and problems requiring a large, interdisciplinary team approach combining the biological sciences, physical sciences, engineering and computing. Arizona has been on the fast track in creating a collaborative environment for success.

To catalyze Arizona efforts, the state heavily invested in advancing its research portfolio at its universities with more than $400 million in capital improvements including: ASU’s Biodesign Institute and Interdisciplinary Science and Technical Buildings (I, II, III); the University of
Arizona’s BIO5; the expansion of the University of Arizona College of Medicine – Phoenix in partnership with Arizona State University; and the new Arizona Biomedical Collaborative building, home of ASU’s School of Biomedical Informatics.

These significant investments have been matched by the recruitment of top scientific talent to fill the research space and jump-start new statewide scientific initiatives. A report from the nonprofit Flinn Foundation assessing education needs in the bioscience arena notes that bioscience and high-tech organizations statewide are increasingly dependent on students trained in interdisciplinary, use-inspired science for expansion, growth and economic success.

“We will put great emphasis on individual mentoring of the students,” says Stephen Albert Johnston, a faculty member in the School of Life Sciences within the College of Liberal Arts and director of the Center for Innovations in Medicine at the Biodesign Institute. “We want their time with the program to be effective – and, therefore, I expect most students to finish in four to five years.”

Students will explore interdisciplinary areas of greatest interest and have a large impact in topics such as biofuels, nanoscience, human-computer interfaces, personalized medicine and infectious disease. Students will have an almost unlimited menu of courses to take from academic units in science and engineering, as well as appropriate training courses in law, policy, sociology and business. This will serve to create a highly flexible degree program focused on preparing student for interdisciplinary careers in science and engineering or the application of science and engineering fundamentals to commercial, legal, political or social realms.
Students will receive a highly competitive stipend, plus full tuition reimbursement and health care benefits.

The program is supported by state funds from the Technology Research Infrastructure Fund, Science Foundation Arizona, and individual investigator research grants.

The deadline for applicants to the fall 2008 program is Jan. 1.

For more information and to apply online, visit the Web site www.biologicaldesign.asu.edu.

Finding link to anthrax, professor set NAU apart

[Source: Anne Ryman, The Arizona Republic] - One of the world's foremost anthrax researchers toils in a cramped, windowless lab at Northern Arizona University.

Inside a locked room only a few can enter, he and his research team study germs so dangerous that the U.S. government considers them top bioterror threats.It was here that Professor Paul Keim made a significant discovery: the 2001 anthrax letter attack on a Florida photo editor came from a genetic strain identical to one developed in U.S. government labs. The finding led the FBI to rule out foreign terrorist attacks in the jittery days after Sept. 11. The FBI called the anthrax letters the worst biological attacks in U.S. history.

Keim's anthrax analysis catapulted his career from niche researcher to the equivalent of a scientific rock star and shone a new light on NAU. His grant funding skyrocketed from less than $1 million to about $8 million a year, and his research on more-common diseases expanded. Soon he will have a new lab to match his world-renowned status. He and his team of 50 researchers are moving into the top floor of a $25 million three-story, glass-and-brick building billed as one of the most energy-efficient in Arizona. The lab space is more than triple what they have now. The building's most talked-about feature, besides the fact it will house anthrax, is the use of recycled blue jeans to insulate the walls. NAU needed to build the lab because of the increased biodefense research workload and more federal safety and security restrictions since 2001.

Keim, 52, has come a long way in six years. In early 2001, he had 25 researchers for his various projects and was among a handful of U.S. scientists who worked on Bacillus anthracis, the bacterium that lives in soil and causes anthrax disease. The lethal germ is considered a top bioterror threat because even a tiny amount of spores, smaller than the head of a pin, can kill if lodged in the lungs.

Keim was well-known in genomics circles, a scientific field that studies genes and their function. In the late 1990s, he and a colleague, Paul Jackson, pioneered a DNA fingerprinting technique to distinguish among the various anthrax strains. The finding revolutionized anthrax research but stopped short of elevating him to the ranks of famous scientists who transcend their fields. Everything changed six years ago when doctors diagnosed Bob Stevens, a photo editor of the supermarket tabloid the Sun, with anthrax.

Fateful call

On the afternoon of Oct. 4, 2001, Keim was in his office when the telephone rang. On the other end was an FBI agent, who told him a plane was on its way to Flagstaff from Atlanta with a culture taken from Stevens' spinal fluid. The FBI wanted Keim to analyze the DNA and find out what type of anthrax Stevens had contracted. This could provide possible clues to where the anthrax originated. Keim broke into a sweat, and his hands tingled. He had expected the call. The FBI knew his reputation, and his NAU lab had the world's largest database of about 2,000 anthrax strains. Four hours later, Keim jumped into his 1990 Toyota 4Runner and made the 15-minute drive to Flagstaff's Pulliam Airport. The setting sun painted the sky red as the small FBI plane landed. A door swung down, and a blond woman stepped out with a cardboard box in her hands."This is the anthrax," she said. The plane and the blonde brought to Keim's mind visions of a famous movie and a moment of humor in an otherwise serious situation. "I'm like Humphrey Bogart in Casablanca," he thought.

The agents filled out paperwork, then handed the box to Keim, who placed it in the back of his 4Runner and drove back to his lab. A glass tube nestled in ice held the culture from Stevens' body. Keim and a couple of his key researchers worked through the night, isolating, processing and magnifying the DNA using machines and computers similar to ones found in crime labs. In the early morning, they compared the results with their anthrax database. They found a match: a virulent type called the Ames strain. The U.S. Army developed the lab strain in the 1980s as a test for the anthrax vaccine.Keim outlined his results the next morning in a conference call with the FBI and the Centers for Disease Control and Prevention in Atlanta.

The media knew nothing of Keim's analysis. Then a few days later, a Florida U.S. attorney held a news conference on the anthrax investigation and said the FBI had sent samples for analysis to NAU. Within 90 minutes, television satellite trucks pulled up and news crews tried to push into his lab. University officials posted 24-hour guards and rushed to install extra locked doors. Hundreds of news reporters left messages on his voice mail. A producer from the Oprah Winfrey Show wanted to have a camera in the lab when Keim discovered who committed the anthrax attacks. "I knew I had made the big time when Oprah Winfrey called," Keim said. He gave no interviews, based on advice from the FBI, which worried that revealing details could jeopardize the investigation and could make him a potential target of whoever committed the crimes. He snuck in and out of his lab using various doors to avoid the media and stopped answering his telephone. He even had a stalker. A woman, convinced she had contracted anthrax, left messages on his voice mail and showed up outside the building. She wanted him to cure her. She called him once from the waiting room of a doctor's office in Prescott, adding "but I still want to see you, Dr. Keim."

Growing reputation

As the FBI investigation progressed, Keim gave limited interviews and confirmed his help to the government. The FBI sent more cultures for analysis. The Los Angeles Times and the Wall Street Journal featured him on their front pages. He spoke before Congress during terrorism hearings. His sudden fame gave a new prominence to NAU, the smallest of Arizona's state universities and the least research-intensive of the three. In the university world, famous scientists lead to more research grants and enhanced prestige. Star scientists help draw other high-ranking scientists and students. "As far as the biosciences go, Paul put NAU on the map, and he continues to do so," said David Engelthaler, a former state epidemiologist who has known him for a decade. Keim stayed down-to-earth with his sudden fame, Engelthaler said. He could talk to top scientists one day and fit in with regular folk at a community event the next day.

Keim's higher profile had an important side benefit for Flagstaff's economy. In addition to his work at NAU, Keim since 2003 has been director of pathogen genomics at the Phoenix-based Translational Genomics Research Institute, or TGen. The non-profit organization opened a new facility, TGen North, in Flagstaff in 2006, and it has grown to employ 14 people. "In a sense, he's an economic-development agent all by himself," NAU President John Haeger said. Yet even as his national reputation grew, he and other researchers faced questions. Investigators speculated that whoever committed the attacks had access to Bacillus anthracis and an intimate knowledge of how the pathogen worked.Scientists came under scrutiny.

The bacterium that causes anthrax is rare. The average person's chances of coming into contact are slim. Anthrax is far more common in animals, and human cases often come from people handling infected animal hides. The anthrax-spiked letters, which sickened 22 and killed five Americans, had been "weaponized." Someone had concentrated the bacterial spores to make them easier to inhale and more lethal. Some mornings, Keim talked to FBI agents about his anthrax analysis. Then in the afternoons, other agents interviewed him about his whereabouts before the attacks. Keim had an alibi. He had been in Arizona, far from the East Coast where the letters were postmarked.

He, like many others, wondered who did it.One night he woke up as his mind raced through possible suspects. He reported his suspicion to the FBI. "They evidently investigated this person, and it wasn't him," Keim said. He declines to say whom he suspected. More than six years after the crime, the FBI has made no arrests.

Research continues

Keim's current lab is in the locked wing of a science building. "You might as well smile for the camera; they're recording you," Keim tells visitors as they go through several locked doors.A sign outside the lab that says "Molecular genetics" hints at the important science going on behind closed doors. Inside, machines hum. Undergraduate students in white lab coats prepare anthrax DNA samples for analysis. Students sit at banks of computers where they read and interpret DNA analysis from the machines. The number of researchers in Keim's lab has doubled since 2001, and their research into other pathogens has expanded. Keim also has a second lab through TGen North near the Flagstaff airport. Keim walks through the NAU lab dressed more like a business executive on a semi-casual day than a scientist, in his chocolate blazer and tan slacks and a blue dress shirt. His schedule is a blur. The previous day he spoke at a biodefense meeting in Boston. On this morning, he gave Arizona legislators a tour of his lab. In two days, he leaves for Thailand, where he has a project with melioidosis, a lethal infectious disease found in Southeast Asia and northern Australia.

Since 2001, his research on other common diseases has expanded. His various projects read like an encyclopedia of illness and disease: valley fever, the staph "superbug," tuberculosis, salmonella, E. coli, plague, sepsis, pneumonia. One grant is aimed at developing DNA fingerprinting for all bacterial pathogen threats. It's not science for science's sake. Faster identification of life-threatening illnesses means doctors can diagnose and treat patients earlier. This year, Keim and his research team got a U.S. patent for a new method to identify various strains of the tuberculosis-causing bacterium. He has similar patents pending for salmonella and E. coli. The Centers for Disease Control and Prevention used his technology to track the recent California spinach E. coli outbreaks. The anthrax attacks created a sort of "war dividend" for public health, Keim said, as scientists use labs and instruments developed for biodefense to also study common diseases."The improvements in public health would never have occurred without the 'anthrax letter' attacks," he said.

Reach the reporter at anne.ryman@arizonarepublic.com or at 602-444-8072.

Tuesday, December 11, 2007

Study finds gene linked to aggressive prostate cancer

[Source: TGen] - Results from two genome-wide association studies have identified a genetic variant of the DAB2IP gene that is associated with the risk of aggressive prostate cancer. Research teams from the Translational Genomics Research Institute (TGen), Wake Forest University School of Medicine, the Karolinska Institute in Stockholm, Sweden, and Johns Hopkins Medical Institutions made the discovery jointly.

Researchers suspect that the DAB2IP gene is involved in tumor suppression, suggesting that this protective mechanism goes awry in men with the variant form. The finding, reported today in the Journal of the National Cancer Institute, might one day help doctors tailor treatment based on a patient's genetic makeup.

Both genetic and environmental factors are important in the development of prostate cancer, and it is only recently that some of the consistent genetic factors have been identified. It is not clear at present whether men who are genetically prone to the disease tend to have more aggressive disease than men who are not. "Because there is no way to tell whether a person has or will have the aggressive version versus the mild version of prostate cancer, both forms are treated the same-with radiotherapy or surgery to remove the prostate gland. The identification of this genetic variant could lead to better risk assessment for aggressive disease, providing doctors with more information on how to best treat men who may be diagnosed with prostate cancer," said John Carpten, Ph.D., director of TGen's Division of Integrated Cancer Genomics and senior author of the paper.

Analysis of 3,159 samples led the researchers to conclude that men possessing the DAB2IP variant appear to carry a nearly 36 percent increased risk of advanced prostate cancer. "In most cases, prostate cancer is not a death sentence, but it would be ideal to identify men with an aggressive form of disease," said Jianfeng Xu, M.D., Dr.PH, a senior author and a professor of epidemiology and cancer biology at Wake Forest University School of Medicine. "Our finding suggests the possibility of developing a blood test to gauge disease type so doctors could decide if more aggressive treatment is needed."

The researchers screened DNA samples from 500 men with advanced prostate cancer and 500 healthy men of the same age in Sweden. This DNA screening examined the entire genome for more than 550,000 single nucleotide polymorphisms (SNPs), which are locations on chromosomes where a single unit of DNA, or genetic material, may vary from one person to the next. The team then focused on 60,000 SNPs that have also been evaluated by a similar study conducted by the National Cancer Institute (NCI) called Cancer Genetic Markers of Susceptibility (CGEMS). Evaluation of these 60,000 SNPs identified seven SNPs that appeared to be linked to disease aggressiveness.

Additionally, researchers screened another 1,242 men with advanced disease and 917 healthy men who were part of a research project at Johns Hopkins Medical Institutions. This group included both African and European Americans. Through these multiple screenings, the researchers found that the variant form of DAB2IP is associated with an increased risk of having aggressive disease.

Senior authors Henrik Gronberg, M.D., Ph.D., a professor of epidemiology from Karolinska Institute, and William Isaacs, Ph.D., a professor of urology at Johns Hopkins Medical Institutions, both agree that the findings were possible because advances in technology allow researchers to take a more systematic approach to looking at the entire genome. Instead of solely studying genes that they suspect may be related to disease susceptibility, they can study the entire genome and look for associations. "By using state-of-the-art technologies, we can find genes that were not previously known or thought to be involved with disease risk," said David Duggan, Ph.D., an Investigator in TGen's Genetic Basis of Human Disease Division. "If we can then learn more about the proteins they produce, it could lead to new understanding about disease mechanisms and new treatments."

Co-first authors on the paper were TGen's Duggan and Siqun Lilly Zheng, M.D., from Wake Forest.

Valutek donation supports TGen's genomic research and discovery programs

[Source: Nanowerk News] - Valutek, a leading solutions provider of products for cleanrooms and controlled environments, has made a $10,000 product donation to the Translational Genomics Research Institute (TGen). The contribution actively supports Phoenix's burgeoning biotech movement and directly benefits TGen's research initiatives. "Valutek has a huge customer base in the biotech industry, and we're thrilled to support an organization that does such noble and exciting work," said Greg Heiland, CEO and President of Valutek. "TGen is on the cutting edge of translational genomics research, and will continue to buoy the emerging biotechnology movement here in Phoenix. We will, in turn, provide products and services to TGen that will fuel this growth."

In-kind donations are a valuable resource for TGen. Gifts like the contribution from Valutek help fund TGen's research, which is focused on developing earlier diagnoses and smarter treatments for many human diseases, including cancer, diabetes and neurological disorders.
According to TGen Foundation President Michael Bassoff, "Valutek's contribution is a meaningful donation that directly and immediately benefits our researchers. TGen is delighted to partner with Valutek and we look forward to working with Valutek in our ongoing research efforts."

Monday, December 10, 2007

New ASU interdisciplinary PhD graduate program in Biological Design set for launch

[Source: Joseph Caspermeyer, Arizona State University] - To help meet the need of Arizona’s booming bioscience sector and create the next generation of highly skilled, interdisciplinary scientists, the Arizona Board of Regents recently approved an innovative ASU graduate degree in Biological Design. The Biological Design PhD degree program seeks to attract and train new scientific talent to use an outcome-driven, interdisciplinary approach in solving major global challenges in human health and the environment. The program is a collaboration between ASU’s Biodesign Institute, Ira A. Fulton School of Engineering, and College of Liberal Arts and Sciences. “The challenges for the next generation of scientists are more complex and inter-related than ever before,” explains Biodesign Institute researcher Neal Woodbury, who directs the institute’s Center for BioOptical Nanotechnology and is a professor in the College of Liberal Arts and Sciences.

“Problems as seemingly unrelated as global pandemics, the need for better medical diagnostics and environmental deterioration all stand to benefit from a convergence of technologies from multiple fields of science. Our goal is to teach students to work in interdisciplinary teams that focus on solving a large-scale problem, rather than working independently on an isolated piece of that problem, which is the more traditional approach,” he said.

The new program reflects ASU’s commitment to “use-inspired” research, one of seven imperatives outlined in 2002 by ASU President Michael Crow as part of the university’s 10-year strategic plan.

An executive committee including individuals from across ASU’s bioscience, engineering, informatics and mathematics academic units spearheaded the effort to create the new PhD program.

According to Biological Design PhD graduate program executive committee member and ASU Professor of Electrical Engineering Trevor Thornton, the main challenge was designing a curriculum to meet the mission of multi-disciplinary, solution-driven research. “An undergraduate curriculum allows a student to gain mastery of an individual discipline,” said Thornton. “The Biological Design PhD program will allow students to apply their core expertise to multi-disciplinary projects, while providing them with the skills they need to work with scientists and engineers from other disciplines.”

The doctoral program consists of a two-semester core course sequence to provide training in bio-related areas. There, PhD candidates will receive intensive training in all the relevant biology-related areas (among them, biophysics, biomedical engineering, biochemistry, molecular biology) combined with emergent disciplines including synthetic biology, systems biology, artificial tissues and drug development.

More than 100 ASU participating faculty will be eligible to mentor students in the program. Initially, 15 students will be recruited each year, generating a total student enrollment in the effort of 60 students by the fourth year.

Science is in the midst of a profound transformation, with increasingly complex data sets and problems requiring a large, interdisciplinary team approach combining the biological sciences, physical sciences, engineering and computing. Arizona has been on the fast track in creating a collaborative environment for success. To catalyze Arizona efforts, the state heavily invested in advancing its research portfolio at its universities with more than $400M in capital improvements including: ASU’s Biodesign Institute and Interdisciplinary Science and Technical Buildings (I, II, III); UA’s BIO5; the expansion of the UA Medical Center in Phoenix in partnership with ASU; and the new Arizona Biomedical Collaborative building, home of ASU’s School of Biomedical Informatics.

These significant investments have been matched by the recruitment of top scientific talent to fill the research space and jump start entirely new statewide scientific initiatives. A report from the nonprofit Flinn Foundation assessing education needs in the bioscience arena notes that bioscience and high-tech organizations statewide are increasingly dependent on students trained in interdisciplinary, use-inspired science for expansion, growth and economic success. “We will put great emphasis on individual mentoring of the students,” said Stephen Albert Johnston, a professor in the School of Life Sciences within the College of Liberal Arts and director of the Center for Innovations in Medicine at the Biodesign Institute. “We want their time with the program to be effective, and therefore, I expect most students to finish in four to five years.”

Students will explore disciplinary areas of greatest interest and have a large impact in topics such as biofuels, nanoscience, human-computer interfaces, personalized medicine and infectious disease. Students will have an almost unlimited menu of courses to take from campus-wide academic units in science and engineering as well as appropriate training courses in law, policy, sociology and business. This will serve to create a highly flexible degree program focused on preparing student for interdisciplinary careers in science and engineering or the application of science and engineering fundamentals to commercial, legal, political, or social realms.

Students will receive a highly competitive stipend plus full tuition reimbursement and health care benefits. The program is supported by state funds from the Technology Research Infrastructure Fund, Science Foundation Arizona, and individual investigator research grants. The deadline for applicants to the fall 2008 program is January 1, 2008. [For more information and to apply online, go to www.biologicaldesign.asu.edu.]

UA details parts of its long-range planning

[Source: Eric Swedlund, Arizona Daily Star] - The University of Arizona is working to redefine its role as a land-grant university with a five-year strategic plan guiding growth and focusing on meeting state needs in research and work-force development. Among the results will be a substantial increase in enrollment overall, particularly for graduate students, a sharp upswing in the number of graduates in teaching and nursing, and a new pledge that low-income students will be guaranteed the financial aid they need.

The university's research mission will continue to focus on current strengths, including biosciences and biotechnology, optics, space exploration and climate, environment, water and energy sustainability. The goal is to increase annual research funding from $552 million to $760 million over the next five years, while increasing the number of endowed faculty chairs from 67 to 100. "The people of Arizona can be assured their land-grant university will pave the way to a successful and prosperous future," said UA President Robert Shelton. "What drives us is serving the people of Arizona and improving the human condition."

Shelton presented the 2007-08 five-year strategic plan to the Arizona Board of Regents Friday at the board's meeting at Arizona State University. The plan was developed by the Strategic Planning and Budget Advisory Committee, chaired by Miranda Joseph, an associate professor of women's studies.

The university will grow to nearly 44,000 students by 2013, with goals of certifying 5 percent more teachers each year, doubling the number of nursing students in accelerated programs, and increasing the number of pharmacy and medical students by one-fifth. Graduate students are expected to make up 25 percent of the overall student body by 2013, up from 21.9 percent now, and Shelton calls for improving the six-year graduation rate from 60 percent to 66 percent and the freshman-to-sophomore retention rate to 90 percent from 80 percent now. "What we have proposed in our plan is a new approach to a storied history of success," Shelton said. "The University of Arizona is poised to redefine the modern land-grant university."

Also Friday, the regents presented an update on their 2020 Plan, a long-term vision for growth in the university system. The work will be finalized by the summer, said Regent Robert Bulla.

Annual undergraduate enrollment at the three state universities has increased by 27 percent — or more than 20,000 students — in the last 13 years, and to move Arizona's educational attainment to a nationally competitive level, annual enrollment would have to increase by 51 percent — or nearly 53,000 — during the next 13 years. The three universities will need to award almost 32,000 bachelor's degrees a year at that time, along with 11,000 master's and 1,500 doctoral degrees. "The ambition is pretty daunting," said Sandra Woodley, chief financial officer for the Board of Regents. "We basically have to double the performance rate of producing baccalaureate degrees in the system."

TGen accelerates cutting-edge cancer cure research using SGI technology

[Source: PRNewswire-FirstCall] - Discovering the differences and changes within the genome that trigger disease is a priority for The Translational Genomics Research Institute (TGen). To aid the non-profit research institute in their quest, TGen deployed technology from SGI to more quickly analyze molecular profile data sets in their search for cancer cures. Purchased in April through a National Institute of Health (NIH) grant, the SGI(R) Altix(R) 4700 will assist TGen researchers in understanding the genomic variation -- a process which requires comparison searches of enormous data sets -- that can be rapidly used for diagnosis and treatment of disease in a manner tailored to individual patients.

TGen selected the SGI Altix 4700 system with over half a terabyte of shared memory so researchers in the Phoenix, Ariz., institute can search across multiple chromosomes, all in memory, without having to break the problems into smaller pieces, enabling researchers to look at the whole instead of the sum of the parts.

While custom in-house code will be written for these large data searches, TGen reports that benchmarks were run on the National Center for Biotechnology Information (NCBI) BLAST (Basic Local Alignment Search Tool), an algorithm for comparing primary biological sequence information, ClustalW, a general purpose multiple sequence alignment program for DNA or proteins, and NAMD, a parallel molecular dynamics code for large biomolecular systems. Testing resulted in performance improvements of up to 50 percent on the 64-bit SGI Altix system as compared to their existing 32-bit system architecture. "Technology, and microarrays specifically, have allowed the size of bioinformatics data sets to become so large that it became vital to acquire a large memory, 64-bit computational infrastructure to be able to manipulate and analyze those files at the level our researchers required," said James Lowey, Director of High Performance Bio-Computing, The Translational Genomics Research Institute. "Conventional 32-bit computer architectures cannot address memory above 4GB. This limitation poses sub-optimal analytical approaches due to the prohibitively protracted computer analysis time needed for optimal mathematical models and computational algorithms."

The molecular profile datasets being analyzed at TGen cover malignant myeloma, melanoma, Alzheimer's, autism and pancreatic, prostate, colon, and breast cancers. With microarrays, each individual file can be up to 150MB. To search and compare genetic patterns, researchers take hundreds and hundreds of copies of that individual file. TGen's code will harness the compute power of the SGI Altix system's global shared memory to run microarrays, searching for variations as minute as a change on one protein, trying to determine what effect that has across the entire spectrum of what is being observed. "The success of TGen scientists to date has come at the sacrifice of time," says Dr. Edward Suh, CIO of TGen. "However, individuals affected with the disease do not have the luxury of time. The 64-bit SGI computing system will optimize TGen researchers' ability to meet their data analysis needs efficiently, hopefully leading to timely and effective discovery for improved human health."

The system will be housed at Arizona State University (ASU) in Tempe, AZ, with operational support provided by ASU's Fulton High Performance Computing Initiative (HPCI). "The shared memory capabilities of the new SGI system provide a welcome addition to the HPC portfolio in Arizona, and will enable researchers at TGen and their collaborators at ASU to address problems we've been unable to tackle in the past," said Dan Stanzione, the Director of the Fulton HPCI.

Purchased through James River Technical, Inc., SGI's designated partner for higher education and research, and installed in late May 2007, the SGI Altix 4700 system at TGen is equipped with 576GB memory and 48 Intel(R) Itanium(R) 2 cores. "We are very excited about the award of the NIH grant to TGen, and the subsequent installation of the SGI Altix system", said Tom Mountcastle, President of James River Technical. "Genomics is a strategic focus for JRT and SGI and the management and processing of large data sets and workflow are ideal fits for the Altix 4700. We are pleased that the system has met the expectations of TGen and we are proud to be a part of the support infrastructure to facilitate this very important research that affects all of our lives."

"TGen's use of SGI technology is another example of SGI's ability to deliver solutions for demanding compute and data-intensive bioscience workflows," said Deepak Thakkar, biosciences segment manager for SGI. "The Altix system's scalability, flexibility and reliability, coupled with its interoperability, provide the best combination of compute, memory and I/O elements, matching the diverse needs of the TGen lab environment."