Friday, October 31, 2008

Corn Researchers Discover Novel Gene Shut-off Mechanisms

[Source: ScienceDaily] - University of Delaware scientists, in collaboration with researchers from the University of Arizona and South Dakota State University, have identified unusual differences in the natural mechanisms that turn off, or “silence,” genes in corn.
The discovery, which was made by comparing the impact of inactivating a gene that occurs in both corn and in the much-studied laboratory plant Arabidopsis, provides new insight into how one of the world's most important crops protects itself from mutation-causing mobile DNA elements and viruses.

The research was led by Blake Meyers, associate professor of plant and soil sciences, and Pamela Green, Crawford H. Greenewalt Chair and professor of plant and soil sciences and marine bioscience, and their laboratory groups at the Delaware Biotechnology Institute, a major center for biotechnology and life sciences research at the University of Delaware.

Collaborating with the University of Delaware team were Vicki Chandler, the Carl E. and Patricia Weiler Endowed Chair for Excellence in Agriculture and Life Sciences Regents' Professor at the University of Arizona, and Yang Yen, a professor at South Dakota State University.

The results were published in the Proceedings of the National Academy of Sciences of the United States of America.

Studies of Arabidopsis thaliana, a small flowering plant of the mustard family that is easy to grow in the lab, have provided a lot of what scientists know about gene silencing in plants.
An important key to the process is short sequences of ribonucleic acids known as “small RNAs” which act like biochemical switches that shut off genes, thus playing a fundamental role in plant development. Understanding how small RNAs work is a continuing quest for geneticists seeking to breed plants with improved crop yields, disease resistance and other characteristics.

Previously, the Meyers and Green labs had studied Arabidopsis plants with nonfunctional versions of a gene known as RNA-dependent RNA polymerase 2 (RDR2). Without an active copy of this gene, the plants were unable to produce a major class of small RNAs, which act to stabilize and protect genes on the chromosomes.

In that prior work, Meyers and Green took advantage of the nonfunctional gene to study microRNAs, an interesting type of small RNA that is usually “masked” by the major class of small RNAs produced by RDR2.

Independently of the UD groups, Chandler and her team at the University of Arizona had identified from corn an orthologous gene--a gene that has the same function in different organisms. In corn, this gene, which the Chandler lab found, is called the mediator of paramutation (MOP1). Its equivalent in Arabidopsis is the RDR2 gene.

Because the RDR2 and MOP1 genes should both produce the “protective” set of small RNAs, the research groups decided to collaborate to see if the small RNAs in corn behave the same way they do in Arabidopsis. The hypothesis was that the result would be the same in the two plant species, and the lab groups could use the MOP1 corn plants to focus their studies on the harder-to-examine microRNAs, as they had done previously in Arabidopsis.

“Yet we found something that had not been observed before in this plant--an odd class of small RNAs,” Meyers said. “I think it's pretty neat to work in a more complex system like corn and see things that Arabidopsis hadn't shown us,” he noted.

Using a technique known as sequencing by synthesis (SBS), provided by Illumina in Hayward, Calif., coupled with state-of-the-art bioinformatics in Meyers' lab, the research team found that the MOP1 and RDR2 genes are not fully equivalent based on an assessment of small RNA complexity.

The researchers found that there are lots more RNAs of an unusual class known as “small interfering RNAs” in corn than there are in Arabidopsis.

“This class of RNAs mainly functions to repress repetitive sequences, including mobile DNA elements called transposons,” Meyers said. “Thus, small interfering RNAs act to protect the genome,” he noted.

“Corn contains an extra layer of protective small RNAs that had not been observed in Arabidopsis, so there must be additional genes other than MOP1 that produce this,” Meyers said.

The scientific community is sequencing the corn genome now, Meyers said. Once the genome is available, the work of matching up small RNAs to specific traits in corn will be much easier, he noted.

“This research is helping us to better understand the biology of corn--one of the most important plants in the world--and gives us new avenues for exploring a novel class of small RNAs,” Meyers said.

Banner to trim costs amid down economy

[Source: Ken Alltucker, The Arizona Republic] - Banner Health, the state's second-largest private employer behind Wal-Mart, will delay the opening of a new hospital in Queen Creek and pursue other cost-savings measures to navigate the slumping economy.

No layoffs are planned for Banner's corporate or hospital staff, but Arizona's largest hospital network will trim costs elsewhere to wring out savings. Planned measures include delaying the opening of its Banner Ironwood hospital under construction in Queen Creek, enforcing time-clock procedures, scaling back uniform purchases and changing its short-term disability policies.

Health care has been one of the few economic bright spots with strong job growth and ambitious expansions over the past few years, but Banner's cutbacks suggest that hospitals are not immune from the slowing economy and Wall Street's tumult.

Banner CEO Peter Fine said the cutbacks are meant to protect the hospital group's financial base.

"Two goals of these actions are to ensure our ability to provide the excellent patient care that is promised in our non-profit mission and preserve as many jobs as possible," Fine wrote in a letter to the hospital group's nearly 35,000 employees. "I and other senior leaders are convinced that we are wise to take these actions now because they can minimize the possibility later of severe actions should the economy worsen."

Banner representatives did not say how much money the hospital group expects to save. The moves are meant to shore up the group's finances for the rest of its 2008 and 2009 budgets.

Banner expanded its reach with more than $1 billion in planned or completed hospital projects through 2010. Expansions included new hospitals such as Banner Gateway Medical Center in Gilbert and new patient towers at Banner Children's Hospital at Banner Desert Medical Center in Mesa and Banner Thunderbird Medical Center in Glendale. In September, Banner completed a $316 million purchase of Sun Health's two-hospital system in Sun City and Sun City West.

The projects solidified Banner's footprint in the Phoenix area, but they come as hospitals face stiff economic challenges.

Many people view health care as a recession-proof industry, said John Rivers, chief executive officer of the Arizona Hospital and Healthcare Association. "What we are seeing today is that it is not," he said.

Hospitals in Arizona and across the nation have been harmed by rising borrowing costs due to Wall Street's credit crunch. A hospital system in Hawaii even blamed the tightening credit market for its recent bankruptcy reorganization.

Banner and Catholic Healthcare West have sought to stem off the credit crunch by refinancing bonds. The Arizona Health Facilities Authority, which issues bonds for non-profit health-care facilities, in August and September issued $1.3 billion in bonds on behalf of Banner to fund the Sun Health acquisition and refinance other higher interest rate instruments.

Catholic Healthcare West also sought to cut costs by delaying equipment purchases, reducing contract labor and cutting discretionary spending. More patients now claim financial hardships at the group's St. Joseph's Hospital and Medical Center.

"We are seeing the downturn," said Sister Margaret McBride, vice president of mission services at St. Joseph's Hospital. "The money that was available is just not available now."

ASU plans to slash nursing enrollment

[Source: Anne Ryman, The Arizona Republic] - Arizona State University plans to cut enrollment at its nursing school because of an anticipated drop in state funding this year, even as the state grapples with a shortage of nurses.

Officials say enrollment will be cut from 80 to 40 students at ASU's Polytechnic campus this spring and by the same amount at the West campus in fall 2009. Enrollment at the downtown Phoenix campus will remain the same.

The cuts apply to students coming into the program and not those currently enrolled.

ASU has about 1,800 students in its nursing program, which officials say is the largest in the nation.

The planned cuts come as ASU officials anticipate the state may slice $25 million or more this year from the university's budget. That would be on top of $30 million in cuts the university already has made. State revenues are down again this year because of a sluggish economy, and the university relies on state funding for about a quarter of its budget.

Cutting back on nursing enrollment is one of several steps university officials are considering.

They also plan to cut 200 or more faculty associates, increase some class sizes, and encourage departments and schools to look for ways to bring in more revenue.

Cuts to the ASU nursing program would run counter to Democratic Gov. Janet Napolitano's stated goal to boost the number of nursing and health-care professionals in Arizona.

Napolitano spokeswoman Jeanine L'Ecuyer cautioned that "the budget process is ongoing" and said no specific cuts have been finalized, but she acknowledged that some "hard, hard" decisions await. State agencies are mulling cuts of their own. The state is facing a shortfall as large as $1 billion for the remainder of this fiscal year, which ends June 30.

ASU is planning now so the school can avoid eleventh-hour cuts. If university officials were to wait until spring, they would be unable to make the cuts in time to help the budget, said Virgil Renzulli, ASU's vice president of public affairs.

The nursing cuts would come at a time when Arizona is struggling with a nursing shortage. Last year, the state had 681 registered nurses per 100,000 people, below the national average of 825 registered nurses per 100,000, according to the U.S. Department of Health and Human Services.
ASU officials on Monday said that the nursing program's total enrollment would stay the same, but on Tuesday, they said that total enrollment is expected to decrease by 80 students. Nursing was chosen because its programs are more expensive to run than those of many other majors.

ASU Provost Elizabeth Capaldi said she hopes it would be a temporary decrease in enrollment that can be reversed when the budget situation improves.

Also on Tuesday, ASU officials backed away from considering expanding lecture-style, general-education classes from 300 to 1,000 students. They said a review of existing classroom space now shows there is not enough room to accommodate that many students in one place. However, increases in size for some smaller classes are likely, they said.

SMCC receives $290,000 grant

[Source: The Arizona Republic] - The South Mountain Community College for Agriculture and Bioscience Education was awarded a $290,000 grant from the U.S. Department of Agriculture.

The three-year Expanding Undergraduate Bioscience Engagement Track (eUBET) grant gives students a chance to conduct biotechnology research projects and publicly present their works. Students in advanced eUBET biotechnology classes conduct rigorous genomics research by mapping genes and publishing. South Mountain is at 7050 S. 24th St.

eUBET is also designed to increase minority-student access to bioscience education and employment and to overcome barriers for high schools to teach biosciences.

The grant will provide partner high schools with a customized package of resources that may include: bioscience laboratory instruments, bioscience training for high school science teachers, college bioscience curricula for the high schools to teach dual enrollment bioscience courses through SMCC, science lab-technician support, lab supplies, student research project materials, student paid internships and science-fair fees.

Partner schools are Phoenix Bioscience High School, Tempe High School, Marcos de Niza High School, Mesa High School's Biotechnology Academy, Corona Del Sol, Carl Hayden Community High School and Arizona Agribusiness & Equine Center.

Two top TGen officials appointed to new positions on the Arizona Technology Council’s board of directors

[Source: TGen] - Dr. Michael Berens and MaryAnn Guerra - two top officials of the Translational Genomics Research Institute (TGen) - have been appointed to new positions on the board of directors of the Arizona Technology Council.

Dr. Berens, Director of TGen's Cancer and Cell Biology Division, was named Chairman Emeritus on the ATC board, one of four new executive officers named to two-year terms. Dr. Berens, who has served six years on the board - the past two as Chairman of the nearly 500-member organization - also was one of five Director's Emeritus named to serve indefinite terms on the board.

"It is an honor to be named by my peers on the board as one of the organization's leaders. My goal is to strengthen the Arizona Technology Council's efforts to grow the state’s knowledge-based industries by helping to promote key national and international business partnerships," Dr. Berens said.

Guerra, TGen's Chief Business Officer and President of TGen Accelerators LLC, was one of 10 new directors appointed to three-year terms on the 33-member board, following its Oct. 23 meeting.

"Being named to the board is an honor, and presents an exciting opportunity to help the Arizona Technology Council work to diversify the state's economic base with high-paying jobs in the fast-growing fields of medicine, technology and innovation," Guerra said.

The board represents the interests of Arizona's technology industries and advises ATC in its expressed goals of promoting research, education and access to a highly skilled workforce.
Three other newly appointed board executive officers are: Chairman Steve Phillips, CIO of Avnet; Secretary Ray Harris Esq., director of Fennemore Craig; and Treasurer Kevin McHolland, CPA and partner of Ernst & Young.

"The Arizona Technology Council has been the principal point of connection for technology companies," Phillips said. "As the new chairman, I will oversee an agenda that continues to build valuable programs and services for all members and supports technology innovation and growth."

Nine other newly appointed directors are: David Beauchamp, partner, Bryan Cave; Thomas Campbell, partner, Lewis and Roca; Kathleen A. Collins, Mesa functional chief engineer, Boeing; John Cummerford, shareholder, Intellectual Property & Technology, Technology, Media & Telecommunications, Greenburg Traurig; Joe Drazek, partner, Quarles and Brady; Carl Lytikainen, senior vice president of Technical Services, Lumension Security; Jane Poynter, president, Paragon Space Development Corporation; Dr. R. F. "Rick" Shangraw, vice president for Research and Economic Affairs, Arizona State University; and Judith K. Weiss, partner, Perkins Coie Brown & Bain.

Four other Director's Emeritus are: Joanne Carthey Bradley, COO, Namescape Corporation; Charles Jirauch, partner, Quarles & Brady LLP; Quinn Williams, shareholder, Greenberg Traurig LLP; and Mark Schonau, CFO, Insysrx.

Steven G. Zylstra, President and Chief Executive Officer of ATC, remains as an executive officer.

Thursday, October 30, 2008

New Campylobacter Vaccine for Poultry

[Source: Susan McGinley, UA College of Agriculture and Life Sciences] - Most people are familiar with Salmonella and its potential to make people ill. But fewer know about Campylobacter jejuni – even though it makes more people sick. Raw chicken is one of the most common carriers of the bacteria, often encountered when cooked meat is placed on unwashed cutting boards previously used for trimming raw chicken, or when chicken is not cooked to 165 degrees Fahrenheit.

"Campylobacter is now the No. 1 food-borne pathogen in the United States and the world, surpassing Salmonella," said Lynn Joens, a professor in The University of Arizona department of veterinary science and microbiology. "In the United States alone, 2.4 million cases are reported annually, with costs exceeding $1 billion."

A new poultry vaccine in development at the UA offers a unique approach in controlling Campylobacter jejuni infection in chickens before it reaches the dinner table. In research trials the vaccine has significantly reduced the pathogen's ability to colonize young chickens' intestines, where the infection begins. The goal is to halt the contamination before it spreads and survives on raw chicken sold in stores.

"Yet chickens don't actually cause the disease (nor does it make them ill). It's the organism they carry that makes people sick," Joens said. "Right now you can go to any grocery store, get a raw chicken, test it in a laboratory and find Campylobacter jejuni. Twenty to 80 percent of all broiler houses become contaminated with Campylobacter."

The most common symptoms of human Campylobacter poisoning, which mimic those of Salmonella and other gastrointestinal pathogens, include fever, cramps, watery diarrhea and sometimes dysentery. More severe infections can lead to peritonitis, autoimmune disease or death.

Funded by the U.S. Department of Agriculture, Joens and UA graduate students started analyzing Campylobacter's infection process about four years ago, looking for a way to interrupt it. The laboratory team, which included graduate research associate James Theoret and assistant research professor Bibiana Law, eventually discovered that the pathogen first attached itself to the surface of the chick's intestines and then began to multiply. Attacking the "sticking" mechanism seemed to be the key.

When the UA researchers sequenced the intestinal surface protein they identified the gene responsible for producing Campylobacter’s adherence protein. Then they built a trial vaccine around it using Salmonella bacteria as a vector, with the assistance of Roy Curtiss, professor and director of the Center for Infectious Diseases and Vaccinology at Arizona State University.

Curtiss’ group inserted the adherence gene into Salmonella bacteria, which is nonpathogenic for poultry. The resulting live vaccine – containing Salmonella programmed to make the Campylobacter adhering protein – was fed to young chickens to protect them.

“Once the Salmonella in the vaccine produced the Campylobacter protein, the chicks made antibodies against it in their intestines,” Joens says. "In our first study of 15 birds we got a very significant reduction – 98 percent – in Campylobacter infection, compared with a control group. We're now repeating the trial on a larger scale."

The vaccination process is simple, easy to produce and protective to the chick, according to Joens. The Salmonella lives four to five days, enough time to stimulate antibody production, and dies. Chickens need to be vaccinated early because they become infected at just two to three weeks of age.

Joens' preliminary figures show that 270 million Campylobacter organisms were present in non-vaccinated birds, compared with 67,000 organisms in the vaccinated birds.

"You need at least 500 organisms to produce disease in humans," he explained. "The chlorine in the packinghouse chillers usually reduces numbers of bacteria by 1,000 to 100,000 organisms, so the chickens should be free of Campylobacter after processing."

The UA group was the first to discover the adherence protein, which is only produced when Campylobacter jejuni colonizes certain surfaces, like chicken intestine and skin. They have a patent pending in both the United States and the European Union for the gene that produces it.
"If everything goes right we could have a commercial vaccine in three to five years," Joens said. The vaccine's effect could be significant: About 8.9 billion broilers go to market annually in the U.S., with a value of $21.5 billion. Europe has similar broiler production figures. Americans consumed 86 pounds of chicken per person in 2006, the most recent numbers available.

"The vaccine would be a great intervention method for Campylobacter when the USDA and FDA (Food and Drug Administration) mandate reduced numbers of food-borne pathogens in chicken – probably in two to three years," Joens said. "Once it becomes available, the vaccine should cost about a penny per chick. More importantly, it should greatly reduce the number of cases of human Campylobacter gastroenteritis."

Drugmaker Roche plans expansion at Ventana

[Source: The Associated Press] - Pharmaceutical giant Roche Holding AG plans to pour $100 million into Oro Valley-based Ventana Medical Systems next year as it pushes to expand its newly acquired subsidiary.

Switzerland-based Roche bought Ventana earlier this year for about $3.4 billion and said it wanted it to play a key role as Roche expands its vision of personalized health care. Ventana develops and sells instruments and chemicals used to automatically prepare tissue samples for cancer screening and the testing of new drugs.

Roche CEO Severin Schwan said at a luncheon on Tuesday that the company plans to increase the southern Arizona work force from about 750 employees to 1,000. He said Ventana is now the headquarters of a Roche global business unit that focuses on diagnostics. He also said during his visit to Tucson that the company plans to expand research and development laboratories at Ventana's campus.

The global drug maker chose Ventana because it's a leader in tissue diagnostics, Schwan said. Ventana's technology can examine cell structure to determine if certain drug treatments will be effective for patients suffering from cancer or infectious diseases.

"The combination of drugs and diagnostics will get much more important as we progress," Schwan said.

The acquisition was completed in February and Ventana has since purchased 17.1 acres for $8.9 million to expand its campus.

Ventana's innovation brought it to Roche's attention, Schwan said, pointing to a genetic test Ventana developed that can show how effectively a certain drug would fight breast cancer.
The drug, Herceptin, is highly effective in 20 to 30 percent of patients, Schwan said. It works when a gene known as HER2 is present in breast cancer tissue specimens.

Ventana developed an automated test that can detect the gene's presence and quantity, which indicates whether a patient may benefit from Herceptin, which is sold in the United States by Genentech Inc. Roche owns a majority of California-based Genentech's stock and has made a bid to buy the rest.

That type of personal health care is potentially a big industry and of great benefit to patients, Schwan said. Knowing if a drug will help or hurt an individual patient is critical, but getting there will be difficult.

"Realizing our vision of personalized health care is an enormous challenge," Schwan said.
Knowing how drugs will work on a patient also saves money, he said.

"You save the unnecessary and costly treatments for those who need it," Schwan said.

Wednesday, October 29, 2008

NSF Grants Nearly $60M for Plant Genome Research Program Awards

Source: GenomeWeb News, a GenomeWeb staff reporter ] - The National Science Foundation has injected $57.3 million into plant genomics studies across the country, and to several international recipients, covering a wide variety of plant life, such as legumes, soil microbes, flower nectar, mutant plants, and other crops.

This round of Plant Genome Research Program studies, in the eleventh year of the program, range from $350,000 to $6.8 million, and vary from two to five years in duration.

These grants will support tool development to advance genomics studies, and the studies will use sequence and functional genomics resources to investigate gene function and interactions between genomes and the environment. These programs will emphasize studies of crop plants that are economically useful such as corn, soybean, wheat, and rice, NSF said.

"Plant biologists continue to make significant conceptual and theoretical advances in our understanding of basic biological processes using plants," James Collins, NSF assistant director for biological sciences, said in a statement. "The latest projects funded through the PGRP reflect this shift and will integrate innovative, cutting edge research with the training of the next generation of plant scientists at both research universities and small teaching colleges and universities.”

These awards will be spread out among a total of 45 institutions in 28 states, and they will support international scientists in Asia, Australia, Europe, and South America. The grants were focused on funding research partnerships between two or more institutions, for example: The University of California, Davis, Cold Spring Harbor Laboratory, and Kansas State University will use $6.8 million to conduct physical mapping of the Wheat D genome. The J. Craig Venter Institute and the University of Wisconsin-Madison will receive $3.8 million to curate the genome of the Medicago truncatula, a legume from the Mediterranean regions commonly used in biology. The University of Southern California and the University of California, Davis, will study the same legume, and will receive $3.2 million to conduct community genomics research into local adaptation of the plant. The University of Arizona and the University of Missouri, Columbia, will use $4.3 million to study comparative functional genomic and proteomic analysis of rhizome specificity across the plant kingdom.

A complete list of the NSF’s PGCSP funding recipients for 2008, and previous years, is available here.

ASU researchers receive NIH awards for studies of malaria and emergent disease

[Source: Bio-Medicine.org] - An Arizona State University research team headed by School of Life Sciences Associate Professor Ananias Escalante will share in more than $6.3 million in awards from the National Institutes of Health for three related studies. Two of the studies will examine the ecology and evolution of malaria and a third will delve into the genetic mysteries behind the host shift of retroviral disease from primates to humans.

Escalante, lead investigator of the malarial studies, will undertake a global comparative study of the evolution of malarial drug resistance, with support from Yuseob Kim, assistant professor, and Maria Pacheco-Delgado, faculty research associate, in ASU's School of Life Sciences. The researchers focus will be on the malarial parasite Plasmodium falciparum.

Worldwide, malaria ranks with tuberculosis and HIV-AIDS among the most important causes of disease and death. Malaria kills a child from somewhere in the world every 30 seconds and is responsible for 350 million to 500 million clinical cases and 1 million deaths each year. According to Escalante, human malaria is endemic in most tropical and subtropical ecosystems worldwide, a burden that poses a significant barrier to global development. Of the four human malarial parasites, P. falciparum and Plasmodium vivax are responsible for most malaria morbidity and mortality.

Escalante and his colleagues seek to understand which types of P. falciparum populations are most prone to the emergence of drug resistance or to the reemergence of drug sensitivity. Investigating how antimalarial drug use selects for resistance is a matter of great interest in evolutionary biology and public health, Escalante says.

"This work will provide good theoretical population genetics models to allow scientists to analyze advantageous mutations and the dynamics of mutations under natural selection in a geographically structured population, " Escalante explains. Such models help the international public health community to better evaluate potential drug policies such as combination therapy or drug rotation in situations likely to be encountered in different endemic areas.

The second study led by Escalante will look at the evolution of P. vivax and Asian macaque malarias. Although this parasite is the most prevalent malarial parasite outside of sub-Saharan Africa, Escalante says that little information presently exists with regard to its genetic diversity. Targeting parasite proteins, either by vaccination or chemotherapeutic drugs, requires an understanding of how the parasites have evolved and the extent and maintenance of their variation.

"Our long-term goal is to link population-level research with comparative genome approaches to understand the origin, demographic history, and genetic diversity of P. vivax at those genes encoding proteins that are involved in the invasion of the red blood cell, a crucial step in the parasite life cycle," Escalante explains. "Our research considers nonhuman primate malarias an important element of the puzzle. We are studying not only well characterized P. vivax and nonhuman primate malaria isolates, but also field isolates from human and nonhuman primate malarias in order to assess the demographic history of the extant populations, explore host-specificity, and assess putative genetic variation that may be under positive selection by the host immune system."

Escalante says that he is "particularly interested in how host switches may lead to molecular adaptations in parasites and pathogens and how the demographic history of parasite and pathogen affects its adaptive variation."

Host shifts are the focus of the third study where Escalante is the ASU principal investigator. This is a project involving multiple investigators and institutions coordinated by Escalante and Lisa Jones-Engel, a field biological anthropologist from University of Washington working on human-primate interactions. In this work, Jones-Engels and Escalante, together with researchers from University of California at Davis and the Fred Hutchinson Cancer Center in Seattle, will examine the evolution, recombination, emergence and exchange of simian retroviruses between human and nonhuman primates. Escalante will also explore the dynamics of nonhuman malarial parasites as part of his vivax-macaque malaria project.

This project will provide valuable information for assessing how human society influences the ecological contexts in which cross-species disease transmission occurs. To date, most research on emerging primate-borne disease has focused on perceived high-risk human populations, such as bushmeat hunters in Africa, and zoo and primate laboratory workers in Western countries. In contrast, little is known about the pathogen exchange between primates in close contact with humans in Asia.

According to Escalante, humans in Asia come into contact with primates in many different ecological contexts besides bushmeat hunting and consumption. There are urban primates, temple primates and wildlife and pet markets. Primates, such as macaques, are also used to harvest coconuts. These complex human-primate interactions increase the potential for cross-species shifts in disease. Jones-Engel and Escalante will be based in Bangladesh with an accessory field site in Indonesia for this work.

Prior to joining ASU, Escalante was a researcher with the Division of Parasitic Diseases at the Center for Disease Control and Prevention in Atlanta, where he still maintains strong ties. His research has had global implications, involving a network of partners in the United States and international collaborators in Bangladesh, Cameroon, India, Indonesia, Kenya, Peru, Tanzania, and Venezuela.

"My long-term goal is to establish bridges among the epidemiological, ecological and evolutionary biology perspectives to address infectious diseases," says Escalante.

"Events such as the Severe Acute Respiratory Syndrome or SARS epidemic and the spread of antimicrobial resistance have increased awareness about the need for incorporating laboratory-based research in decision-making processes that involve public health," Escalante explains.

"Molecular information, together with concepts from ecology and evolutionary biology allows the public health community to test hypotheses and explore scenarios that otherwise could not be investigated by traditional epidemiological approaches."

Ultrasound Shown To Exert Remote Control Of Brain Circuits

[Source: ScienceDaily] - In a twist on nontraditional uses of ultrasound, a group of neuroscientists at Arizona State University has developed pulsed ultrasound techniques that can remotely stimulate brain circuit activity.

Their findings, published in the Oct. 29 issue of the journal Public Library of Science (PLoS) One, provide insights into how low-power ultrasound can be harnessed for the noninvasive neurostimulation of brain circuits and offers the potential for new treatments of brain disorders and disease.

While it might be hard to imagine the day where doctors could treat post traumatic stress disorders, traumatic brain injury and even Alzheimer's disease with the flip of a switch, most of us have in fact experienced some of ultrasound's numerous applications in our daily lives. For example, ultrasound has been used in fetal and other diagnostic medical imaging, ultrasonic teeth cleaning, physiotherapies, or surgical ablation. Ultrasound also provides a multitude of other non-medical uses, including pharmaceutical manufacturing, food processing, nondestructive materials testing, sonar, communications, oceanography and acoustic mapping.
"Studies of ultrasound and its interactions with biological tissues have a rich history dating back to the late 1920s," lead investigator William "Jamie" Tyler points out. "Several research groups have, for more than a half-century, demonstrated that ultrasound can produce changes in excitable tissues, such as nerve and/or muscle, but detailed studies in neurons at the cellular level have been lacking."

"We were able to unravel how ultrasound can stimulate the electrical activity of neurons by optically monitoring the activity of neuronal circuits, while we simultaneously propagated low-intensity, low-frequency ultrasound through brain tissues," says Tyler, assistant professor of neurobiology and bioimaging in the School of Life Sciences in the College of Liberal Arts and Sciences.

Led by Tyler, the ASU research group discovered that remotely delivered low intensity, low frequency ultrasound (LILFU) increased the activity of voltage-gated sodium and calcium channels in a manner sufficient to trigger action potentials and the release of neurotransmitter from synapses. Since these processes are fundamental to the transfer of information among neurons, the authors pose that this type of ultrasound provides a powerful new tool for modulating the activity of neural circuits.

"Many of the stimulation methods used by neuroscientists require the use and implantation of stimulating electrodes, requiring direct contact with nervous tissue or the introduction of exogenous proteins, such as those used for the light-activation of neurons," Tyler explains.
The search for new types of noninvasive neurostimulation methods led them to revisit ultrasound.

"We were quite surprised to find that ultrasound at power levels lower than those typically used in routine diagnostic medical imaging procedures could produce an increase in the activity of neurons while higher power levels produced very little effect on their activity," Tyler says.

Other neuroscientists and engineers have also been rapidly developing new neurostimulation methods for controlling nervous system activity and several approaches show promise for the treatment of a wide variety of nervous system disorders. For example, Deep Brain Stimulation (DBS) and Vagal Nerve Stimulation (VNS) have been shown to be effective in the management of psychiatric disorders such as depression, bipolar disorders, post-traumatic stress disorder, and drug addition, as well as for therapies of neurological diseases such as Parkinson's disease, Alzheimer's disease, Tourette Syndrome, epilepsy, dystonia, stuttering, tinnitus, recovery of cognitive and motor function following stroke, and chronic pain. Up until now, these two techniques have captured the attention of physicians and scientists; however, these therapies still pose risks to patients because they require the surgical implantation of stimulating electrodes. Thus, these types of therapies are often only available to patients presenting the worst of prognoses.

One prior stumbling block to using ultrasound noninvasively in the brain has been the skull. However, the acoustic frequencies utilized by Tyler and his colleagues to construct their pulsed ultrasound waveforms, overlap with a frequency range where optimal energy gains are achieved between transcranial transmission and brain absorption of ultrasound – which allows the ultrasound to penetrate bone and yet prevent damage to the soft tissues. Their findings are supported by other studies examining the potential of high-intensity focused ultrasound for ablating brain tissues, where it was shown that low-frequency ultrasound could be focused through human skulls.

When asked about the potential of using his groups' methods to remotely control brain activity, Tyler says: "One might be able to envision potential applications ranging from medical interventions to use in video gaming or the creation of artificial memories along the lines of Arnold Schwarzenegger's character in 'Total Recall.' Imagine taking a vacation without actually going anywhere?

"Obviously, we need to conduct further research and development, but one of the most exhilarating prospects is that low intensity, low frequency ultrasound permit deep-brain stimulation procedures without requiring exogenous proteins or surgically implanted medical devices," he adds.

Tyler and the other ASU researchers will now focus on further characterization of the influence of ultrasound on intact brain circuits and translational research, taking low intensity ultrasound from the lab into pre-clinical trials and treatment of neurological diseases.

New Supercomputer Can Do 50 Trillion Operations Per Second

[Source: ScienceDaily] - In less time than the blink of an eye, the Translational Genomics Research Institute's new supercomputer at Arizona State University can do operations equal to every dollar in the recent Wall Street bailout.

That would be 700 billion computations in less than 1/60th of a second, says Dan Stanzione, director of the High Performance Computing Initiative at ASU's Ira A. Fulton School of Engineering.

The "Saguaro 2" supercomputer, housed on the first floor of ASU's Barry M. Goldwater Center for Science and Engineering, is capable of 50 trillion mathematical operations per second.
"That's the equivalent of taking a calculator and doing one operation per second, by hand, continuously for the next one and a half million years," Stanzione said.

Although the computing world changes daily, and measurements depend on numerous factors, Stanzione said, for some functions, ASU's new computer may be among the top five in the world.
TGen will need that speed as it continues its research into a variety of human diseases through the use of data-rich DNA sequencing, genotyping, microarrays and bioinformatics.

"This is really a remarkable testament," to the cooperative efforts of ASU and TGen, said Dr. Jeffrey Trent, President and Scientific Director of TGen, especially in a tight funding environment.

The new supercomputer will help TGen's efforts in translational biomedicine, developing new therapies targeted for individual patients suffering from Alzheimer's, autism, diabetes, coronary heart disease, melanoma, pancreatic cancer, prostate cancer, colon cancer, multiple myeloma, and breast cancer.

Dr. Edward Suh, TGen's Chief Information Officer, said a joint TGen-ASU computer support team is being assembled, and he urged the creation of more partnerships between TGen and ASU.

"I am confident this new supercomputer system will help the ASU and TGen scientists expedite their research, and accelerate innovation in biomedical and engineering research," Suh said. "It is my hope to see this supercomputer system, and a supporting informatics program which Dan and I are putting together, bring the ASU and TGen scientists closer than before for even greater success."

Saguaro 2 – a partially water-cooled set of 7-foot-tall black monolith computer racks, each with as many as 512 processor cores, and linked by ultra-high-speed Infiniband cables – was funded in part by a nearly $2 million grant in July by the National Institutes of Health. The grant was in response to a wide range of scientific activities proposed by TGen, the Ira A. Fulton School of Engineering, and ASU's BioDesign Institute.

The new system doubles the capabilities of ASU's High Performance Computing Initiative (HPCI). The system consists of Intel microprocessors, servers from Dell, storage from Data Direct Networks, and components from a number of other partners, including fiber optic cables from Phoenix-based Zarlink.

More importantly for TGen, the new system has 20 times the previous computational power available to TGen researchers, said James Lowey, director of TGen's High Performance Biocomputing Center.

The new supercomputer also adds to the storage capacity of the HPCI, bringing the total storage to 1.5 quadrillion bytes, or 1.5 petabytes -- or 15 followed by 14 zeroes (1,500,000,000,000,000). That's enough storage space to record nearly a quarter million DVD discs.

The HPCI storage will be used to store a vast array of data from TGen's sequencers and simulations, as well as other large datasets from ASU researchers, including a high resolution mapping of the moon to be performed in 2009 by NASA's Lunar Reconnaissance Orbiter.

"As we move in science into the nano scale of materials and molecular design and diagnostics, or into the macro scale of global climate or the motion of the galaxies, experimentation becomes more expensive and difficult, and simulation becomes invaluable," Stanzione said. "The speed of those simulations determine the speed of progress."

The computational speed of Saguaro 2 is especially critical to the work of TGen. "In 2009, more genome sequence data will be generated than all the words spoken by humans in all of history. Teasing meaningful understanding from this avalanche of data is also the role of HPC (high performance computing)," Stanzione said.

Toward Non-invasive Disease Diagnosis With Wellness Cards

[Source: ScienceDaily] - Scientists are reporting development of a device that could serve as the electronic "reader" for a coming generation of "wellness cards," specimen holders used to diagnose disease from a drop of a patient's saliva or blood. The research, done by scientists in Utah, Iowa, Arizona, and Minnesota, is presented in two papers in ACS' Analytical Chemistry.

In those studies, Marc Porter and colleagues describe using the same technology at the heart of miniaturized hard disk drives to create the new rapid-screening sensor. Using a phenomenon known as giant magnetoresistance (GMR), the device can detect samples on much smaller areas compared to older technologies, the papers note.

As a test, Porter demonstrated the GMR sensor could detect as few as 800 magnetic beads with microscopic dimensions. "Several laboratories have begun to transition GMRs from the data storage domain to that of the bioanalytical sciences," the paper states. "We believe that, by leveraging advances made in the magnetic recording industry (for example portable digital music players), a robust, field-deployable, assay device capable of sensing single-binding events is just over the horizon."

Monday, October 27, 2008

Science programs worth cost

[Source: Jeffery Trent: My Turn, The Arizona Republic] - The Translational Genomics Research Institute helps Arizona students pursue a lifetime of science learning

Recently published results from this spring's first science test administered by Arizona's Instrument to Measure Standards (AIMS) showed only 38 percent of Arizona high-school students passed.

Without judging the validity or necessity of AIMS or its pilot science program, there is substantial evidence that Arizona's and America's schoolchildren are lagging behind much of the developed world in science instruction

The most recent international comparisons published by the U.S. Department of Education show that American 15-year-olds ranked 29th of 57 nations surveyed in science literacy.

But it doesn't have to be that way. Science doesn't have to be a chore. As science advocates from Carl Sagan, Mr. Wizard (Don Herbert) and Bill Nye, the Science Guy, have shown, science can be fun - even hip.

Organizations such as Yale's Women in Science and the Howard Hughes Medical Institute have mentoring programs that show early exposure to the process of discovery can pay lifetime dividends in commitment and knowledge.

To sustain Arizona's growing biotechnology industry, it is important to understand the impact of science in our lives; on decisions with profound implications for issues as varied as climate change, health care and the economy.

Scientific literacy is key to understanding today's technologically advanced world. And providing for the needs of scientifically empowered citizens begins with education.

One way to foster learning and develop a love of science is internship programs, in which experts mentor students who are immersed in scientific inquiry and the creation of new insights.

TGen hosts the Helios Scholars Program, which recently received $6.5 million to fully fund the program for 25 years from the Phoenix-based Helios Education Foundation.

Each summer, 45 Helios Scholars participate in eight-week internships. TGen scientist-mentors actively engage high school, undergraduate and graduate students in research projects, including new ways to treat cancer, diabetes, autism and Alzheimer's disease.

These programs work. Some of TGen's interns include:

• Anne Lee and Albert Shieh, the first Arizona high-school students to win the team competition for the internationally recognized Siemens Westinghouse Competition in Math, Science and Technology. They developed new software that more accurately analyzes genetic data, resulting in a shared prize of $100,000.
• Shannon Fortin, an Arizona State University graduate in biochemistry, who received a $7,500 Goldwater Scholarship, as well as a Fulbright Scholarship to spend nine months in Belgium researching brain cancer.
• Graduates of TGen's Helios program have gone on to attend some of the most prestigious schools in the nation, including Harvard, Massachusetts Institute of Technology, Georgetown and Stanford, as well as ASU, University of Arizona and Northern Arizona University.

TGen is not alone in this movement. Other Arizona science education efforts:

• Gov. Janet Napolitano in September announced the establishment of the Arizona STEM Education Center, housed within Science Foundation Arizona in downtown Phoenix. STEM (science, technology, engineering and mathematics) goals follow the Arizona Bioscience Roadmap, which urges "a more informed citizenry in the biosciences and encourage(s) young people to explore and pursue scientific and technical careers."
• Phoenix Union Bioscience High School began in 2007, providing a unique, four-year science education with opportunities for as many as 400 students a year to collaborate with downtown Phoenix's academic and scientific communities.
• The Biotechnology Laboratory for Arizona Students and Teachers (BLAST), established in 2006 at the Tucson Magnet High School, provides instruction at a state-of-the-art-equipped molecular-biology laboratory.
• ASU's School of Life Sciences Undergraduate Research (SOLUR) program since 2004 has provided opportunities Valley-wide for students to participate in exciting biological research.

Internships and other educational programs are both time-consuming and costly. But the investment is critical to our recognizing a brighter future for all Arizonans.

Dr. Jeffery Trent is president and scientific director of the Phoenix-based Translational Genomics Research Institute.

Company picks Valley to develop skin products

[Source: Ken Alltucker, The Arizona Republic ] - Sunshine and skin damage have prompted a San Diego biotechnology company to expand in Arizona to develop a line of anti-aging skin products.

Histogen Inc. has opened a Tempe office and plans to begin selling three new skin-care products in the first quarter of 2009.

The company said it uses a stem-cell-like technology to foster a skin product derived from skin discarded from infants after circumcisions.

The company wants to parlay revenue collected from the sale of aesthetic products to fund research in areas such as cardiovascular and wound healing.

It's the same playbook sketched out by other Arizona biotechnology companies such as Tucson-based Niadyne Development: develop anti-aging skin products backed by science to raise cash while focusing on a bigger prize of health research.

The Tempe division is called Histogen Aesthetics.

President Lawrence Rheins said the company chose Arizona to launch its aesthetics business due to the Phoenix-area's large network of dermatologists and plastic surgeons focused on cosmetic and anti-aging procedures as well as the state's growing biotechnology hub.

"Everybody who lives here gets photo (sun) damage," said Rheins, who previously served as a director at Hill Top Research in Scottsdale and an assistant dermatology professor at the University of Cincinnati. "There is a real need for these types of products because of the desert climate and the intense sun."

Histogen CEO Gail Naughton was the co-founder of Advanced Tissue Sciences, a former San Diego biotech company that had a promising skin-patch technology to treat burns and wounds.

The company eventually filed bankruptcy amid heavy debt and a struggle to get Food and Drug Administration approval for a key product.

Naughton, now a dean of the college of business administration at San Diego State University, has reloaded with Rheins and several of her former Advanced Tissue colleagues.

Of Histogen's first 25 employees, 18 worked together at Advanced Tissue, Rheins said.
"It is clearly the reason we were able to start as fast as we were able to," he said.

Histogen's Tempe office has four employees, with plans to expand to about 20 workers as the company launches its line of skin products targeting baby boomers and others. The positions will mainly be sales and marketing.

Rheins said the company expects its non-prescription products will be sold by plastic surgeons and dermatologists and distributed by a Tempe company, Secure Medical. Secure Medical CEO John Rao also sits on the board of Histogen, and Secure Medical is an investor.

Histogen's products will be made from an ingredient the company calls ReGenica, which can be used for skin, hair and nail care.

The company said its technology mimics the embryo, allowing the growth of protein-rich material that is similar to what is found in young skin.

Rheins said the company's initial products will include a gel that can be applied to skin after laser resurfacing. It also will unveil anti-aging lotions that are applied day and night.

Earlier this year, Histogen unveiled a kit to grow stem cells, called BioNuesis.

The Tempe division expects to expand with other skin offerings such as dermal fillers or treatments for skin conditions such as acne or rosacea.

Rheins said Histogen has no plans to conduct research at its Tempe office, but the company may conduct clinical trials here.

The parent company, which formed last year, believes the technology can be used to eventually have many beneficial therapeutic uses, including regenerating cells that can help treat cardiovascular patients and heal wounds.

Arizona receives federal DNA grant

[Source: Judy Nichols, Sandra Day O’Connor College of Law] - The Arizona Justice Project and the Arizona Attorney General’s Office have been awarded a $1.4 million grant from the U.S. Justice Department through its National Institute of Justice. The grant will be used for post-conviction DNA testing in cases of forcible rape, murder, and non-negligent manslaughter to demonstrate actual innocence.

Under this grant, Arizona could become one of the first states in America to systematically and categorically identify inmates in which DNA might resolve questions about actual innocence, and then conduct the needed testing.

“This grant affords us a very exciting opportunity,” said Carrie Sperling, executive director of the Arizona Justice Project and a professor at the Sandra Day O'Connor College of Law, where the project is housed. “This is a huge and important undertaking and the opportunity to collaborate with all of the relevant agencies in the state is very exciting.”

Over the next 18 months, the Arizona Justice Project will identify and evaluate potential cases and, with the help of the Attorney General’s Office, will secure the relevant biological evidence and the necessary files.

Attorney General Terry Goddard said the grant will help make sure the right people are convicted.

“DNA testing is a powerful tool that benefits all involved in our criminal justice system, especially victims,” Goddard said. “This grant enables my office to support local prosecutors and ensure that those who have committed violent crimes are identified and behind bars.”

The Arizona Justice Project and the Attorney General’s Office will work with Arizona’s crime labs – both public and private –under the grant administration of the Arizona Criminal Justice Commission.

Arizona’s crime laboratories will make their resources available both for examination of samples and for conducting comparison testing through the national database of DNA profiles. Several private laboratories also have been identified to assist in the collaborative effort, including the Chromosomal Laboratories located in Phoenix.

The Project also will use private investigators through the Arizona Association of Licensed Private Investigators.

The Project will continue with its criminal justice endeavors and case evaluations in many other areas.

“We look forward to devoting special attention to this undertaking and the partnership with Arizona’s law enforcement and forensic communities,” Sperling said.

More than 200 exonerations in the United States have resulted from DNA evidence, two of them in Arizona. Most of these exoneration cases are brought forward by inmates through private attorneys or non-profit organizations, such as the national Innocence Project or state organizations such as the Arizona Justice Project. The principals of this grant-funded post-conviction DNA project will document the processes with the goal of making this a best practice to be replicated in other states that allow for post-conviction DNA testing.

The Arizona Justice Project, an innocence project, is now in its 11th year and is now centered at the College of Law, which enjoys a national reputation as a center for the study of forensic science and DNA research and evaluation. For many years the Project also has worked in concert with the James E. Rogers College of Law at the University of Arizona and with the Northern Arizona University Justice Project.

Panel weighing UA overhaul's proposals faces daunting task

[Source: Aaron Mackey, ARIZONA DAILY STAR] - One day into a review of roughly 75 proposals to make the UA more efficient, those charged with sorting through the ideas see a monumentally confusing task before them.

While there are several large-scale plans to merge colleges or create new ones at the University of Arizona, most of the proposals deal with smaller department-level changes that are directly connected to proposed changes at the college level.

The web of connections between many of the proposals — on top of several that overlap or contradict each other — is forcing committee members to rethink how they'll evaluate the ideas before offering up final recommendations to administrators in November.

To make matters even more difficult, some of the proposals argue for the status quo, in a sense rejecting UA President Robert Shelton's call for a massive overhaul of the university's operations in the face of declining state support.

Shelton in September said that the UA needed to change how it teaches students, conducts research and serves the state so that the institution could continue to increase its academic prestige and streamline operations.

He called on faculty, staff and students to submit proposals on how to meet those goals, with the ideas being made public on Tuesday.

They range from small moves, such as blending two majors into one, to large-scale mergers of some of the UA's most research-intensive colleges.

A subcommittee of the Strategic Planning and Budget Advisory Committee met on Wednesday to discuss the larger proposals.

While some of the college-level proposals were discussed, members of the committee quickly realized that many of the smaller proposals connected to larger changes and needed to be examined at the same time, said Miranda Joseph, the subcommittee's chairwoman.

Instead of focusing on the big proposals first, the committee will group together all ideas — big and small — and then try to examine their potential, Joseph said.

For example, perhaps the largest proposal calls for the colleges of Optical Sciences, Engineering and Science to merge into one massive unit.

The proposal for the move only briefly touches on how the many departments and schools within the colleges would fit together, relying instead on other proposals to flesh it out.

Those proposals call for a handful of new schools or departments, including a new School of Earth and Atmospheric Sciences that would merge programs such as hydrology, mining and tree-ring research.

But not every small proposal fits in neatly with larger ideas. One, for example, calls for the centralization of all the physical-sciences classes on campus.

In that model, physics would be at the center of the teaching, collaborating with other fields such as chemistry and optical sciences.

It's not clear how the proposal would fit in with the current college structure or any of the proposed college-level changes.

Making matters even more complicated for the committee is that there are several colleges and departments that argue they should remain unchanged.

In a proposal from the College of Optical Sciences, it's clear that leaders don't believe mergers with another college or department is necessary.

Instead, the college proposes to help teach a few more physics and math classes while helping other departments and colleges boost their research funding.

Similar calls to remain unchanged are echoed in proposals by the College of Fine Arts and the University College, which serves students who haven't picked a major.

By arguing for the status quo, the colleges could be seen as potential roadblocks to several other ideas being considered by the committee.

In the case of Optical Sciences, the college is at the heart of a handful of other proposals that involve merging all or parts of it with other colleges.

On top of the example mentioned earlier, another proposal recommends merging Optical Sciences with Engineering to allow for greater collaboration.

The competing proposals among the science colleges are just a glimpse of the types of wide-ranging, often contradictory ideas that the subcommittee will have to reconcile in the next two weeks.

While Joseph said there won't be changes made merely for the sake of shaking things up, she's hopeful the committee will be able to identify ideas that will make the UA better and meet Shelton's goal.

"We're looking for proposals where there's a meaningful benefit, where change is worthwhile," Joseph said.

On StarNet: Keep up with other happenings around the University of Arizona with the Campus Correspondent blog at go.azstarnet.com/campuscorrespondent

Radiation Therapy Oncology Group and US Oncology Enter Collaboration to Increase Patient Access to National Clinical Trials

[Source: Collaboration Brings Cooperative Group Level Radiation Therapy Trials to US Oncology Affiliates' Patients for First Time

The Radiation Therapy Oncology Group (RTOG) and US Oncology, Inc. today announced they have entered into a collaboration to increase patient access to national cancer clinical trials with a radiation focus in the community setting.

The collaboration means patients receiving cancer care at practices affiliated with US Oncology have access to RTOG trials for disease sites including brain, head & neck, lung, gastrointestinal, genitourinary, cervix, and breast cancers. RTOG trials focus on testing the integration of radiation therapy with new systemic therapies and surgery.

The collaboration also marks the first time US Oncology, as a network of member practices, has participated in cooperative group trials in radiation oncology. In addition, US Oncology is the first multi-state, national organization to become an affiliate member of RTOG. Current members include large regional practices and academic practices with several facilities in metropolitan areas.

"Our collaboration with US Oncology and its network of member practices is attractive due to the organization's strong commitment to clinical trial participation, leadership and accrual," said Walter Curran, MD, Group Chairman of RTOG and professor and chairman of the Department of Radiation Oncology of Emory University School of Medicine. Dr. Curran also serves as Chief Medical Officer of the Winship Cancer Center at Emory University. "We were confident their track record as a multi-site organization with significant accruals in a variety of clinical trials would be a good fit," said Dr. Curran.

Following infrastructure development to centralize the IRB, data collection, reporting, credentialing and quality assurance to operate as a network, US Oncology was granted affiliate member status in the RTOG late last year.

The collaboration began with 10 US Oncology affiliated practices working as a network; due to interest from radiation oncologists, the number expanded to 14 sites. The participating affiliated practices include: Texas Oncology practices at Sugar Land, Medical City Dallas, Sherman, Methodist Dallas, Klabzuba, and Bedford Harris; Kansas City Cancer Center's North, South, and Southwest sites; Willamette Valley (Oregon) Cancer Center; Central Indian Cancer Center-South; Arizona Oncology Associates-Tucson; Rocky Mountain Cancer Center-Aurora, and New York Oncology Hematology-Albany.

The first US Oncology patient was enrolled in an RTOG trial in March 2008. From March to mid-October of this year, a total of 17 patients from eight fully credentialed sites have been enrolled, exceeding the minimum requirement of five enrolled patients during the first year of membership. Among the eight sites, an average of six studies are open to enrollment at any given time.

Benefits for patients participating in the radiation therapy trials include increased access to new investigational therapies, the state-of-the-art in standard care, and close monitoring by physicians and other clinicians during the trial.

US Oncology has developed a robust medical oncology research program over the past 12 years. Affiliated radiation oncologists expressed the desire to increase the breadth of the research network and provide patients with access to radiation therapy combined modality studies to offer an integrated care environment for patients.

"We are excited about the relationship between Radiation Therapy Oncology Group and US Oncology," said Vivek Kavadi, MD, medical director of radiation research for US Oncology. "You have one of the nation's foremost cancer treatment and research networks working with the premier organization for radiation trials to provide a clinical offering beneficial to patients and both organizations."

The collaboration provides RTOG access to US Oncology's significant patient population, making radiation therapy trials more accessible to cancer patients in the community setting nationwide. US Oncology's strong presence in certain parts of the country helps RTOG expand clinical trial participation into areas where it has few or no enrolling members, giving patients access to trials previously unavailable to them.

"We at Radiation Therapy Oncology Group are always interested in opportunities to expand our portfolio of trials to the greatest number of patients and we are excited that US Oncology's investigators will help us in that mission," said Dr. Curran.

US Oncology affiliated practices participating in the RTOG trials program have increased access to new investigational radiation therapy treatments, and the ability to work with other oncologists and leading researchers to advance the quality of care for cancer patients.

"We're on a substantially strong growth track with the RTOG trials," said Dr. Kavadi. "We hope to have 30 affiliated practices participating by next year, and to become a full RTOG member by early 2010. We're delighted this relationship is going to be a central part of the overall growth for the US Oncology Research network."

Diatom Genome Helps Explain Their Great Diversity and Success in Trapping Excess Carbon in Oceans

[Source: Deborah Daun, BIO5] - Diatoms, mighty microscopic algae, have profound influence on climate, producing 20 percent of the oxygen we breathe by capturing atmospheric carbon and in so doing, countering the greenhouse effect. Since their evolutionary origins these photosynthetic wonders have come to acquire advantageous genes from bacterial, animal and plant ancestors enabling them to thrive in today’s oceans. These findings, based on the analysis of the latest sequenced diatom genome, Phaeodactylum tricornutum, are published in the October 15, 2008 edition of the journal Nature by an international team of researchers led by the U.S. Department of Energy Joint Genome Institute (DOE JGI) and the Ecole Normale SupĂ©rieure of Paris. The research team includes Carolyn Napoli, PhD, a research professor with the BIO5 Institute; and Rich Jorgensen, PhD, professor of plant sciences at The University of Arizona.

The researchers compared Phaeodactylum with the diatom Thalassiosira pseudonana, previously sequenced by DOE JGI, revealing a wealth of information about diatom biology, particularly the rapid diversification among the hundreds of thousands of diatom species that exist today. Phaeodactylum was targeted for sequencing due to its value as a diatom model, given the ease with which it can be grown in the lab and the availability of tools to genetically transform it, and the comparisons with the previously sequenced diatom genome of Thalassiosira pseudonana.

“These organisms represent a veritable melting pot of traits—a hybrid of genetic mechanisms contributed by ancestral lineages of plants, animals, and bacteria, and optimized over the relatively short evolutionary timeframe of 180 million years since they first appeared,” says first author Chris Bowler of the Ecole Normale SupĂ©rieure. “Our findings show that gene transfer between diatoms and other organisms has been extremely common, making diatoms ‘transgenic by nature’,” he adds.

The wholesale acquisition of genetic material has provided food for thought to researchers bent on characterizing the diatom’s staying power and ability to cope with environmental change.

“We believe this is the first time bacterial horizontal gene transfer has been observed in eukaryotes at such scale,” says senior author Igor Grigoriev of DOE JGI. “This study gets us closer to explaining the dramatic diversity across the genera of diatoms, morphologically, behaviorally, but we still haven’t yet explained all the differences conferred by the genes contributed by the other taxa.”

From plants, the diatom inherited photosynthesis, and from animals the production of urea. Bowler speculates that the diatom uses urea to store nitrogen, not to eliminate it like animals do, because nitrogen is a precious nutrient in the ocean. What’s more, the tiny alga draws the best of both worlds—it can convert fat into sugar, as well as sugar into fat—extremely useful in times of nutrient shortage.

The team documented more than 300 genes sourced from bacteria and found in both types of diatoms, pointing to their ancient origin and suggesting novel mechanisms of managing nutrients—for example utilization of organic carbon and nitrogen—and detecting cues from their environment.

Diatoms, encapsulated by elaborate lacework-like shells made of glass, are only about one-third of a strand of hair in diameter. “The diatom genomes will help us to understand how they can make these structures at ambient temperatures and pressures, something that humans are not able to do. If we can learn how they do it, we could open up all kinds of new nanotechnologies, like for building miniature silicon chips or for biomedical applications,” says Bowler.

Diatoms reside in fresh or salt water and can be divided into two camps, centrics and pennates. The centric Thalassiosira resemble a round “Camembert” cheese box (only much smaller) and pennates like Phaeodactylum look more like a cross between a boomerang and a narrow three-cornered hat—hence the species name, tricornutum. Not only is their shape and habitat diverse, so too is their behavior; for instance, the former get around by floating, the latter by gliding through the water or on surfaces.

The lifestyle of diatoms can be characterized as “bloom or bust.” When light and nutrient conditions in the upper reaches of the ocean are favorable, particularly at the onset of spring, diatoms gain an edge and tend to dominate their phytoplankton brethren. When food is scarce, they die and sink, carrying their complement of carbon dioxide to the deeper recesses.

Bowler and his colleagues are also trying to understand the role that iron plays in the Phaeodactylum’s development. Iron is even more precious than nitrogen in the ocean and its absence in the southern hemisphere is likely a major cause of oceanic deserts of photosynthesis there. Bowler’s team has demonstrated that when iron deficiency occurs processes such as photosynthesis and nitrogen assimilation are suppressed. Other studies, which hail diatoms as champions in capturing carbon dioxide, suggest a bold strategy of using iron as a fertilizer to provoke massive diatom blooms. “Once they have feasted, the weight of their silicon shells, which resemble glass, causes the diatoms to sink to the bottom of the ocean when they die, and the carbon that they assimilated is trapped there for millennia,” says Bowler. “By sequestering carbon in this way we could reverse the damage from the burning of fossil fuels.”

Other DOE JGI authors on the Nature study include Alan Kuo, Robert Otillar, Asaf Salamov, Chris Detter, Erika Lindquist, Susan Lucas, Harris Shapiro, Daniel Rokhsar, and Igor Grigoriev as well as Jane Grimwood and Jeremy Schmutz of JGI at the HudsonAlpha Institute.

The U.S. Department of Energy Joint Genome Institute, supported by the DOE Office of Science, unites the expertise of five national laboratories -- Lawrence Berkeley, Lawrence Livermore, Los Alamos, Oak Ridge, and Pacific Northwest -- along with the HudsonAlpha Institute for Biotechnology -- to advance genomics in support of the DOE missions related to clean energy generation and environmental characterization and cleanup. DOE JGI’s Walnut Creek, CA, Production Genomics Facility provides integrated high-throughput sequencing and computational analysis that enable systems-based scientific approaches to these challenges.

UA researchers are finding a new way to reduce food-borne illness in humans

[Source: Susan McGinley, UA College of Agriculture and Life Sciences] - Most people are familiar with Salmonella and its potential to make people ill. But fewer know about Campylobacter jejuni – even though it makes more people sick. Raw chicken is one of the most common carriers of the bacteria, often encountered when cooked meat is placed on unwashed cutting boards previously used for trimming raw chicken, or when chicken is not cooked to 165 degrees Fahrenheit.

"Campylobacter is now the No. 1 food-borne pathogen in the United States and the world, surpassing Salmonella," said Lynn Joens, a professor in The University of Arizona department of veterinary science and microbiology and a BIO5 member. "In the United States alone, 2.4 million cases are reported annually, with costs exceeding $1 billion."

A new poultry vaccine in development at the UA offers a unique approach in controlling Campylobacter jejuni infection in chickens before it reaches the dinner table. In research trials the vaccine has significantly reduced the pathogen's ability to colonize young chickens' intestines, where the infection begins. The goal is to halt the contamination before it spreads and survives on raw chicken sold in stores.

"Yet chickens don't actually cause the disease (nor does it make them ill). It's the organism they carry that makes people sick," Joens said. "Right now you can go to any grocery store, get a raw chicken, test it in a laboratory and find Campylobacter jejuni. Twenty to 80 percent of all broiler houses become contaminated with Campylobacter."

The most common symptoms of human Campylobacter poisoning, which mimic those of Salmonella and other gastrointestinal pathogens, include fever, cramps, watery diarrhea and sometimes dysentery. More severe infections can lead to peritonitis, autoimmune disease or death.

Funded by the U.S. Department of Agriculture, Joens and UA graduate students started analyzing Campylobacter's infection process about four years ago, looking for a way to interrupt it. The laboratory team, which included graduate research associate James Theoret and assistant research professor Bibiana Law, eventually discovered that the pathogen first attached itself to the surface of the chick's intestines and then began to multiply. Attacking the "sticking" mechanism seemed to be the key.

When the UA researchers sequenced the intestinal surface protein they identified the gene responsible for producing Campylobacter’s adherence protein. Then they built a trial vaccine around it using Salmonella bacteria as a vector, with the assistance of Roy Curtiss, professor and director of the Center for Infectious Diseases and Vaccinology at Arizona State University. Curtiss’ group inserted the adherence gene into Salmonella bacteria, which is nonpathogenic for poultry. The resulting live vaccine – containing Salmonella programmed to make the Campylobacter adhering protein – was fed to young chickens to protect them.

“Once the Salmonella in the vaccine produced the Campylobacter protein, the chicks made antibodies against it in their intestines,” Joens says. "In our first study of 15 birds we got a very significant reduction – 98 percent – in Campylobacter infection, compared with a control group. We're now repeating the trial on a larger scale."

The vaccination process is simple, easy to produce and protective to the chick, according to Joens. The Salmonella lives four to five days, enough time to stimulate antibody production, and dies. Chickens need to be vaccinated early because they become infected at just two to three weeks of age.

Joens' preliminary figures show that 270 million Campylobacter organisms were present in non-vaccinated birds, compared with 67,000 organisms in the vaccinated birds.

"You need at least 500 organisms to produce disease in humans," he explained. "The chlorine in the packinghouse chillers usually reduces numbers of bacteria by 1,000 to 100,000 organisms, so the chickens should be free of Campylobacter after processing."

The UA group was the first to discover the adherence protein, which is only produced when Campylobacter jejuni colonizes certain surfaces, like chicken intestine and skin. They have a patent pending in both the United States and the European Union for the gene that produces it.

"If everything goes right we could have a commercial vaccine in three to five years," Joens said. The vaccine's effect could be significant: About 8.9 billion broilers go to market annually in the U.S., with a value of $21.5 billion. Europe has similar broiler production figures. Americans consumed 86 pounds of chicken per person in 2006, the most recent numbers available.

"The vaccine would be a great intervention method for Campylobacter when the USDA and FDA (Food and Drug Administration) mandate reduced numbers of food-borne pathogens in chicken – probably in two to three years," Joens said. "Once it becomes available, the vaccine should cost about a penny per chick. More importantly, it should greatly reduce the number of cases of human Campylobacter gastroenteritis."

TGen spin-off MedTrust Online enables cancer doctors to quickly obtain best-available treatment information

[Source: TGen] - TGen has spun off its third company: MedTrust Online, a reliable one-stop medical information source for oncologists.

The for-profit, privately held MedTrust Online draws on a variety of data sources, including genetic-based medical discoveries by the non-profit, Phoenix-based Translational Genomics Research Institute.

Scottsdale-based MedTrust Online aims to provide oncologists with the knowledge they need to design the best tailor-made treatments for individual patients.

"MedTrust Online is the first, comprehensive Internet-based solution that enables physicians to practice precision medicine," said Chris Yoo, MedTrust's President and Chief Executive Officer. “We provide clinically-useful knowledge to help physicians find and communicate with each other about cutting-edge cancer treatments for the benefit of their patients."

MedTrust Online is the third company to spin out of TGen Accelerator Management LLC, a firm designed to quickly translate TGen’s genetic research discoveries into medical treatments and services.

"While MedTrust is our third spin-off company, it is a first in the informatics area for TGen Accelerator, and marks a beginning in the effort to use the vast knowledge generated by TGen scientists for the commercial benefit of doctors and the general public," said MaryAnn Guerra, TGen's Chief Business Officer and President of TGen Accelerator Management.

Richard Love, a former TGen Chief Operating Officer and former CEO of ILEX Oncology Inc., praised the advent of MedTrust as a boost to the local economy.

“The creation of MedTrust is part of the promise TGen holds for helping Arizona develop local biomedical expertise, jobs and productive venture partnerships," said Love, now a Manager for Translational Accelerator LLC, or TRAC, an Arizona-based bioscience venture capital group. "I personally believe that MedTrust can have a bigger positive impact on patient care than anything I've seen come along over the past decade."

TGen and MedTrust Online signed licensing and services agreements Aug. 5 covering TGen-generated technologies and personnel.

MedTrust Online solution will help speed information to oncologists as they seek the best knowledge available about various diseases, especially quality information about potential drug therapies.

The MedTrust Online's Electronic Curbside Consult provides doctors with a platform for discussing difficult cases with experts and promotes peer-to-peer collaboration.

Also, MedTrust has formed a partnership with the South Texas Oncology and Hematology, one of the Southwest's leading cancer care providers. STOH is assisting MedTrust in creating its web site, www.medtrust-online.com, which is expected to go public to doctors starting in December.
In addition, MedTrust has added two key executives to its management team:

-- Dr. Leo Otake, a widely published graduate of the Yale University School of Medicine. Otake has been named Vice President of Medical Informatics. Otake’s primary responsibilities include coordinating the collection, organization and distribution of MedTrust Online content, including peer-reviewed medical journals and pharmaceutical databases. He also will be in charge of managing relationships with oncologists and advisers.

-- Russell J. Clark, an attorney with an extensive background in conducting cancer data analytics and creating proprietary tools to identify and analyze patterns of care. Clark has been named Executive Vice President of Business Development. Clark’s primary responsibilities include developing business opportunities and recruiting doctors to subscribe to MedTrust.

Clark has more than 25 years of experience in health care, legal and business ventures.

UA Departments of Chemistry and Biochemistry and Molecular Biophysics to Merge

[Source: Johnny Cruz, University Communications] - Faculty in The University of Arizona's departments of chemistry and biochemistry and molecular biophysics have overwhelmingly agreed to develop a plan to merge their respective departments, instantly creating one of the nation's most highly ranked chemistry departments.

The new department of chemistry and biochemistry will rank among the top 12 such departments in the country – as measured by federal research expenditures. There are approximately 160 doctoral degree-granting chemistry and biochemistry departments in the country, and most of them share a similar model to the new UA department.

The combined departments will form a teaching and research powerhouse, along with becoming the UA's third largest teaching program – behind only mathematics and English.

"The University Transformation gives us an opportunity to better position the disciplines represented by many departments around campus by aligning the strengths of the disparate units," said Joaquin Ruiz, dean of the UA College of Science. "There is perhaps no better example of this than the merger of the departments of chemistry and biochemistry and molecular biophysics. This merger will elevate the national ranking of the new unit, but more importantly will allow for exciting new opportunities in research and teaching."

The new department will house more than 650 undergraduate majors and 210 Ph.D. students – with combined teaching in excess of 40,000 student credit hours per year.

"Both of the faculty and staff groups merging are incredibly strong in research and teaching, as well as service," said Mark Smith, head of the UA department of chemistry. "Many of the ways we compete for resources depend on being able to project a formidable strength, and this merger will accomplish just that."

Smith also believes that the merger will enhance the UA's ability to compete with the nation's most prestigious institutions for the very best students, faculty and staff. "For perhaps the first time, chemistry and biochemistry at the UA will be recognized as the research and teaching leaders they are," Smith said.

"I have been a member of the two departments (chemistry and biochemistry and molecular biophysics) for the past 8 years and have experienced firsthand the great strengths that each department brings to the proposed merger," said Vicki Wysocki, head of the UA department of biochemistry and molecular biophysics. "This is an excellent example of bringing together two different cultures to form a new department that will be stronger than the sum of the parts."

When combined, the new department will attract approximately $16 million annually in federal research support to department research groups, which interact with faculty from nine other UA colleges. Chemistry and biochemistry faculty have collaborative research programs with UA researchers in optical sciences, astronomy, planetary science, the BIO5 Institute, molecular and cellular biology, medicine and other departments.

"This merger is about excellence, and it exemplifies the spirit of what the UA is striving for through the Transformation Plan," said Meredith Hay, UA executive vice president and provost. "These two strong departments joining forces will result in an exceptional unification of talent, greater quality through more collaborative research and more opportunities for our students through the combined resources of chemistry and biochemistry."

The teaching program will include undergraduate and graduate degrees in the traditional fields of chemistry and biochemistry as well as an accelerated master's degree, a graduate degree and distance learning programs for science teachers. The department also will continue educating medical school students and will join forces to become the UA's largest Ph.D. program.

The nationally ranked faculty in chemistry and biochemistry and molecular biophysics will continue performing research over a broad range of molecular science, which includes areas such as solar energy, chemistry of the planets and interstellar space and intervention in disease.

According to Smith, the merger will promote the best training of future scientists and technologists that will help Arizona to solidify its economic base. "It is strength in science that will help the state of Arizona weather the economic storm," Smith said.

Chemistry and biochemistry and molecular biophysics have been separate departments at the UA since 1977.

Answering the Question: ‘Which Drug Therapy Is Right for Me?’

[Source: Karin Lorentzen, AHSC Office of Public Affairs] - In the world of pharmaceutical science, the question of why two very similar individuals can react differently to a drug is the subject of intense interest.

At The University of Arizona College of Pharmacy, researchers are striving to find answers to seemingly simple questions asked by patients, such as, "Why did I have to try three different high blood pressure medications before my doctor found one that worked for me?" and "Why did my cancer stay in remission with drug treatment, but my friend who had the same treatment was not so fortunate?"

At the basis of the answers to these questions is a field of study called pharmacogenomics, the analysis of how the expression of the human genome, the DNA code that instructs the making of the machinery of a cell, is key to the body's response to drugs.

"Importantly," said Walt Klimecki, assistant professor at UA College of Pharmacy, "pharmacogenomics helps us understand why two apparently similar individuals could have very different responses to the same drug. It holds the promise that drugs might one day be tailor-made for individuals and adapted to each person's own particular makeup."

In his lab at the UA's BIO5 Institute, Klimecki and Alicia Bolt, a graduate student in pharmacology and toxicology, are conducting pharmacogenomic research on a collection of white blood cells taken from about 200 healthy individuals from diverse global populations in the United States, China and Africa. The cells have been manipulated experimentally so that they can easily be grown in a plastic flask with growth media. Klimecki stores stocks of these individuals' cells in a lab freezer at the BIO5 Institute – a "town in a tube," he said.

This system allows Klimecki and Bolt to explore the diversity of individual variation in drug response in a much more controlled way than could be possible with the short-lived samples taken directly from human study participants.

In the lab, Klimecki and Bolt expose the white blood cells to arsenic trioxide, a relatively recent addition to the cancer-treatment arsenal in the United States, to measure how different expression patterns of the genome can predict response to this anti-cancer drug.

To measure differences in drug response, they use a technology called microarrays, a highly miniaturized analysis technology that allows scientists to measure the levels of each and every product contained in the master recipe book that is the human genome. For example, on one typical microscope slide, 44,000 such products can be measured four separate times.

Bolt reported he results of the research this month at the Mountain West Society of Toxicology meeting. In her abstract, Bolt states that a frequent observation in humans is the scenario of a relatively uniform toxicant exposure that is associated with a variable response. "The results are exciting," said Bolt. "Our observations suggest that this cell line model reproduces the inter-individual variation seen in arsenic-induced cell-killing observed in humans."

"Our research to date is encouraging," Klimecki said, "but these are complicated problems to solve. We need to study the effects of both genetics and the environment. The long-term solutions to these complex problems are going to involve multidisciplinary teams that include pharmacist-scientists, pharmacologists, toxicologists, chemists and computational/statistical scientists. But the results will be worth the work. These approaches and tools are an important part of the movement away from ‘trial-and-error' drug selection to the more individually targeted drug choices that are on the horizon."

Caste in the colony

[Source: EurkaAlert] - "The history of all past society has consisted in the development of class antagonisms…the exploitation of one part of society by the other". – Karl Marx and Frederick Engels, The Communist Manifesto.

Although diversity in social groups can increase group well being, it also may increase the potential for conflict. All societies are characterized by struggles for control: which individuals gain the spoils and which toil in the fields. In colonies of social insects this struggle is embodied by a reproductive division of labor. Some individuals (the queens) reproduce, while the workers provide the labor that maintains colony function. In many social insects queens enjoy nearly complete control over reproduction and workers have diversified in form and function to increase their efficiency at performing different labors.

How, then, is it determined which individuals, as developing larvae, becoming queens or different types of workers? A collaborative research team of scientists at four universities has found that caste determination in the Florida harvester ant is much more than meets the eye. Larvae become different castes (small workers, large workers, or new queens) based largely on the nutrition they receive. Those fed more insects than seeds are more likely to become larger individuals (queen>large worker>small worker). However, genetic differences also contribute and bias the larva's developmental pathway. Even once caste is determined, nutritional, social (colony size), and genetic factors all contribute, but in different ways, to how big an individual grows. "Caste determination in most social insects likely involves both nature and nurture, but most interestingly in this species, these two forces contribute differently in different castes," says lead researcher Chris R. Smith of the University of Illinois. Although genetic factors contribute to what caste an individual becomes, the environment of the larva is controlled by the workers. Quite generally, ant colonies are supreme examples of both conflict and cooperation – each extreme of the nature-nurture continuum.

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"Caste determination in a polymorphic social insect: nutritional, social, and genetic factors" by C.R. Smith (University of Illinois Urbana-Champaign), K.E. Anderson (University of Arizona), C.V. Tillberg (Linfield College), J. Gadau (Arizona State University), and A.V. Suarez (University of Illinois Urbana-Champaign). American Naturalist (2008) 172:497-507 DOI: 10.1086/590961

Making Flies Sick Reveals New Role For Growth Factors In Immunity

[Source: ScienceDaily] - Salmonella infection is not a positive experience. However, by infecting the common laboratory fruit fly Drosophila melanogaster with a Salmonella strain known for causing humans intestinal grief, researchers in the School of Life Sciences at Arizona State University have shed light on some key cell regulatory processes – with broad implications for understanding embryonic development, immune function and congenital diseases in humans.
Associate Professor Stuart Newfeld and laboratory coordinator Joel Frandsen, along with colleagues in the College of Liberal Arts and Sciences and Biodesign Institute at ASU, released their findings online on September 24 in the journal Proceedings of the National Academy of Sciences.

Strong parallels exist in the regulation of immune system function in animals as diverse as flies, mice, and humans. Newfeld's own investigative connection between fly and human immune systems came about through his research with a well-studied family of proteins called Bone Morphogenetic Proteins (BMP).

"Bones and flies?" one might scoff. These proteins are named because of their involvement in the formation of bone and cartilage in humans; however, they have also been linked to many other aspects of early development and to essential cellular processes in virtually all animals.
One type of morphogenetic protein, intensively studied in fruit flies and the focus of the published study by the Newfeld group, is the growth factor Decapentaplegic (Dpp). Dpp acts as a hormonal signaling device, binding to cells and communicating, for instance, whether to divide or to stop growing or even to become a different type of cell.

Studies have shown that Dpp in the fruit fly and its counterparts in other animals have diverged little from one another in evolutionary time. Although there are tiny changes in the genes that code for this protein from animal to animal, the morphogenetic proteins are still structurally and functionally very similar – a testament to their crucial role as signaling devices in all animals, including humans.

"Dpp from flies has been shown to be completely functional in mammalian cells, and the human version of Dpp – BMP 2/4 – also works just fine when injected into flies," explains Newfeld.

Newfeld's research builds on earlier observations made by Aaron Johnson, then a graduate student in the Newfeld lab, now a postdoctoral fellow with University of Texas Southwestern Medical Center in Dallas, Tex. Johnson first observed that fruit fly mutants that lacked the ability to generate Dpp protein in one tissue (at a particular time in embryonic development) suffered from excess cell growth in the neighboring tissue. The lack of communication between the tissues resulted in uncontrolled cell growth, in this case in the heart. "Dpp mutant flies have large hearts which are stiffer and beat inefficiently," says Newfeld.

Johnson went on to uncover Dpp's role in heart development. He discovered that when the embryo is nearly ready to hatch, Dpp signals tell heart cells to stop growing. These instructions also insure a proper boundary between the heart and surrounding muscle tissue.

While these were fundamentally exciting discoveries, Newfeld made them even more so when he extended Johnson's project. Since both the heart and the lymph glands in the fly originate from the same tissue (cardiogenic mesoderm), he postulated that when heart development goes awry in fruit fly Dpp mutants that the lymph glands might also be affected.

"One of the functions of the lymph gland in fruit flies is to produce blood cells," notes Newfeld. "This is in contrast to humans where the processes take place in our bone marrow."

With support from Science Foundation Arizona, Frandsen built on Johnson and Newfeld's early discoveries by looking into the mutant fruit fly's immune system and blood cells. He noticed that, in addition to excess cell growth during heart development, Dpp mutants also had an excess of plasmatocytes (blood cells involved in digesting small infectious particles) – an important clue that Dpp was affecting the regulation of the immune system of the flies.
Plasmatocytes are one of three types of immune cells that arise from hematopoietic stem cells – embryonic cells that only take on their adult roles based on signals they receive from signaling molecules, including Dpp. However, how Dpp might specifically function in blood cell formation remained a mystery, and required fresh thinking.

With help from School of Life Sciences Professor Roy Curtiss, director of the Center for Infectious Diseases and Vaccinology at the Biodesign Institute at ASU, and his technician Bronwyn Gunn, Frandsen and Newfeld developed a novel experimental approach. Rather than curing their fly patients, they sought instead to make the Dpp mutants sick, hoping the infection with Salmonella would provide a new avenue to study their immune system defects in greater detail.

"The problem with the traditional approaches to studying immunity is that we keep our flies in a pretty clean lab – they see few, if any, pesticides or parasites or anything they would need to defend themselves from," says Newfeld.

Getting flies sick wasn't trouble free, Frandsen says. At first, the fruit flies wouldn't eat the type of Salmonella that infects humans. But, with some clever cookery, a feeding technique was identified that led to Salmonella-infected flies. Once inside the flies, the Salmonella activated their immune systems. Newfeld points out that it was then that Frandsen made a key observation: Dpp mutant flies are unable to produce one type of immune cell that normal flies do in response to an attack by pathogens. This was the first piece of evidence that Dpp might regulate the options available to hematopoietic stem cells.

The lack of Dpp in fly mutants meant that their stem cells would only become plasmatocytes. The inability of Dpp mutant fruit flies to produce a particular immune cell type was not obvious under regular lab conditions. This type of defect is considered "cryptic"; a defect that is not immediately obvious because until the fly requires an immune response there is no way to know that something is wrong.

"Up to this point Dpp had not been implicated in hematopoiesis in flies," states Newfeld.
The discovery that Dpp plays a direct role in immune system regulation in flies may have some direct implications for humans, offering new insight into human diseases caused by mutations in bone morphogenetic proteins. Newfeld says too, that scientists who study these morphogenetic proteins in mammals (proteins very similar to Dpp) have known for some time that these proteins are involved in the hematopoietic stem cell growth in the bone marrow. The similarities between the two organisms are intriguing.

"These are exciting parallels; ones which can stimulate collaboration, provide inspiration and reveal new research directions relevant to the understanding of development and immune diseases," Newfeld notes.