ASU News - Bioscience / Biotech

Young biochemist seeks to discover medical breakthrough

dfossum — Thu, 04 Sep 2008 23:00:00 -0600

Conor Cox, a biochemistry major in the College of Liberal Arts and Sciences, came to ASU for its numerous research opportunities and immense resources.

As for his decision to go into biochemistry, Cox acknowledges his high school biology class. As part of the class, the teacher required all students to participate in an internship. “I interned with a virologist microbiologist,” says Cox. “This piqued my interest in molecular biology. And after completing two semesters at ASU, I knew that I had made the right decision.”

When asked how he came to participate in undergraduate research at ASU, Cox mentioned that he had heard a lecture concerning evolution at a meeting of the ASU Student Affiliates of the American Chemical Society (SAACS). After talking to some professors, he came to find that Neal Woodbury of the Biodesign Institute was doing research in this area. “I jumped right in,” says Cox, “and it has worked well.” Woodbury is now Cox’s advisor.

Matt Greving, a graduate research associate at the Biodesign Institute, is his immediate mentor. “He helps me learn the procedures that I am not familiar with,” says Cox, “and is teaching me how to analyze the data which is being generated by this project.”

At its core, the research Cox is working on involves discovering ways to bind peptides selectively to proteins. Peptides are small chains of amino acids, and proteins are large folded chains of peptides that make up much of our bodies. “Currently, I am working to determine where on a protein a peptide binds and how this binding location changes with mutations.”

To begin this research, Cox selects a peptide which has specific binding characteristics. Then, Greving takes that peptide and alters it randomly to see what mutations optimize it. Then, the mutated and original peptides are bound to a protein. By treating the mix with a few chemicals and enzymes, Cox and Greving wipe out everything but the protein piece bound by the peptide.

“We then use a mass spectroscopy device to discover the weight of the bound portion,” says Cox. “This allows us to discover the biding site of a given peptide on a given protein, and allows us to examine how the mutations, which allow a peptide to bind better, chemically improve that binding.”

Cox and his mentor hope to discover why peptides bind where they do on proteins and how this can be improved by less difficult methods than guess and check. If successful, the research could also allow for a big change in medical diagnostics, drug design or medical treatment regimens. “If we can design a peptide that only binds to one protein, or even one spot on the protein, nearly anything in the body can be targeted by it,” says Cox, “If it can be targeted, it can hopefully be destroyed or changed which will aide is fighting disease, infection and the like.”

“Conor is a talented student with the ability to analyze and explain unexpected results from complex experiments,” says Greving. “His rapid success in research is providing him an opportunity to be a key part of scientific publications related to the work, which will make Conor a very strong candidate for graduate school. I'm sure Conor has a very successful scientific career ahead of him.”

Cox hopes to continue this research throughout his undergraduate career and is looking into Neuro-Biochemistry for graduate school. He is interested because it seems like a field where researchers try to answer the philosophical question “Why are humans the way they are?” in the most accurate and scientific way possible. “I am interested in anything that involves society and the nature of human interaction,” he says.

Moreover, his ambitions and achievements have not gone unnoticed. He was recently awarded the CRC Handbook Award for top (out of state) undergraduate in chemistry and is currently receiving a National Merit Scholarship at ASU. He also has made the CLAS Dean’s list every semester. “I have not yet won any scholarships for research,” he says. “Hopefully next year that will change!”

Cox also enjoys practicing martial arts at ASU and is interested in materials science and media studies, especially copyright and the nature and growth of the internet. “Basically,” he says, “I really like complex things that grow and adapt to the conditions placed on them and manage to work around those conditions to form unique behaviors.”

He has a philosophy that applies both to his work and his personal goals. “In research you think something will work, you test it and you work the kinks out and test it again. If it works go with it. If it fails, try something new,” he says. “That is the way I try to live life.”

Algae-based technology nets $3 million in funding

sjkeele1 — Tue, 02 Sep 2008 17:45:09 -0600

Arizona State University has entered into a groundbreaking research and commercialization collaboration with Heliae Development, LLC and Science Foundation Arizona (SFAz) to develop, produce and sell kerosene-based aviation fuel derived from algae.

Arizona Technology Enterprises (AzTE), the technology venturing arm of ASU, announced the initiative today.

This biofuel project will focus on the commercial production of kerosene from algae using patented technologies developed by Professors Qiang Hu and Milton Sommerfeld at ASU’s Laboratory for Algae Research & Biotechnology.

The research efforts of Hu and Sommerfeld in algal-based biofuels and biomaterials have already moved from the laboratory to field pilot-scale demonstration and production. Their pioneering discoveries have demonstrated significant cost-reduction benefits when compared with traditional methods of producing kerosene from petroleum.

Hu and Sommerfeld have identified specific algal strains that can convert a significant portion of their cellular mass into a type of oil that is a group of “medium-chain fatty acids”. The oil produced by these particular algae is high in concentration of medium-chain fatty acids, which, after deoxygenation treatment, closely mirrors the length of the hydrocarbon chains found in what is commonly called kerosene.

Kerosene, when mixed with minor amounts of fuel additives, is known as JP8 or Jet A, which is suitable for use in jet aviation applications. A competitive advantage of the medium-chain fatty acid-based kerosene production is elimination of an expensive chemical or thermal cracking process, which is otherwise necessary for long-chain fatty acids commonly found in animal fat, vegetable oils, and typical algae oils.

Heliae Development, LLC (Heliae) was recently formed by several out-of-state private equity investors (including individuals who are members of an extremely successful private family business with a long-standing commitment to the environment) for the purpose of licensing and developing these algal strains for jet fuel. The company will lease space at SkySong, the ASU Scottsdale Innovation Center.

Under the license agreement with Heliae, AzTE will receive an equity stake in the company along with other standard forms of consideration including licensing fees and a share of any commercialization income. In addition, Heliae will provide research funding of $1.5 million to ASU to support further development of the specific algal strains towards commercial production of jet fuel. The Heliae funding will be matched dollar for dollar by a Strategic Research Group award from SFAz, so that ASU will receive a total of $3 million for the project.

“The world needs sustainable alternative fuel sources, and most critically the airline industry,” said Frank Mars, coordinating investor in Heliae. “Each year, more than 600 million barrels of kerosene-based fuels are refined from petroleum for the U.S. military and commercial jet fleets. Our goal is to help ensure that ASU’s world leading research in this field gets developed to a point that algae is seen as a cost-effective, real-world alternative to our dependency on fossil fuel. Our willingness to partner with ASU on this important project was facilitated by its flexibility and innovativeness in structuring the kind of collaborative relationship necessary to look long term and to advance technologies into the marketplace.”

“The partnership with Heliae and SFAz reflects ASU’s leadership and research efforts to bring high-value renewable energy sources to the market in an expedient manner,” added ASU president Michael Crow. “We are supporting an innovative portfolio of multidisciplinary approaches for discovering alternative energy sources that are cost-effective and carbon-neutral. The jet fuel initiative is another example of the high-impact research being conducted by ASU researchers to find disruptive solutions to complex environmental and global problems.”

“We are pleased to support this cutting-edge collaboration between ASU and Heliae to develop aviation fuel from algae,” said William C. Harris, president and chief executive officer of SFAz. “At a time when significant policy issues are being raised about the sustained viability of using food stocks to produce biofuel, ASU researchers are at the forefront of renewable energy technologies that conserve high-value land.”

John Mars, an individual investor in Heliae, noted that “this jet fuel initiative with ASU comes at a critical point in the world’s search for alternative fuels that are truly sustainable over the long term. We welcome the opportunity to support this endeavor.”

According to Charlie Lewis, AzTE’s vice president for venture development, “ASU’s investments in photosynthesis and bioenergy research are starting to lead to commercial opportunities for investors and companies searching for green technologies. We already have spin-out companies and industrial collaborations in these areas.”

With numerous programs and projects to address global environmental issues and challenges, Arizona State University is among the world’s leading research universities in the area of sustainability. Home to the nation’s first School of Sustainability and the Global Institute of Sustainability (GIOS), ASU has research initiatives in solar energy, biofuels, and fuel cells. Its bioenergy portfolio (http://biofuels.asu.edu) includes the following areas: biofuels using algae and cyanobacteria as feedstocks; biomimetic photovoltaics & artificial photosynthesis; novel catalysts; biohydrogen from cyanobacteria; novel fuel cells; and methanogenesis and increased bioavailability.

Located at SkySong, Arizona Technology Enterprises was established in 2003 as an Arizona limited liability company whose sole member is Arizona State University Foundation. Staffed by professionals with extensive industry and university experience in intellectual property and related business development, AzTE operates as the exclusive IP management and technology transfer organization for ASU. For more information about AzTE, visit www.azte.com.

SkySong, the ASU Scottsdale Innovation Center, is currently home to 35 enterprises from 11 countries, with clusters of companies in e-learning, information communications technologies, and sustainability. SkySong is an interactive business environment in which individual entrepreneurs, global enterprises, ASU researchers, and community members connect to bring new technologies to the marketplace and expand globally.

Algae fuel makes splash at international show

ckussala — Mon, 11 Aug 2008 12:51:45 -0600

Researchers Qiang Hu and Milton Sommerfeld from ASU’s Department of Applied Biosciences recently flew to London to share their findings and research on the application of algae-based oils for creating biofuels at the Farnborough International Air Show.

The exhibit was part of a collaboration and ongoing relationship between the researchers and aviation giant Boeing.

While many exhibits showed off the latest improvements on turbines and designs for commercial aircraft and jet fighters, the researchers ended up stealing the show and attracting numerous visitors to their booth.

The star attraction of the Boeing exhibit was a 75-gallon tank of bright green algae.

The tank was, in fact, a bioreactor – a “feeding ground” container that promotes accelerated algae growth. The exhibit was the high note of a one-year relationship between the ASU researchers and Boeing.

The company has committed a $225,000 grant to support ongoing algae research at ASU, and to provide three scholarships for graduate students.

“The experience was very positive, because most shows are too technical for the public,” Hu says. “With the live algae, we can explain to children and families how algae grow, and how we extract the oil and convert it to jet fuel.”

Hu and Sommerfeld were a big hit with children – and they also attracted the attention of aviation business leaders and engineers.

The two researchers earned an immediate nod from Boeing to keep a presence at the air show.

“Not many people knew about ASU,” Sommerfeld says. “However, they expressed great interest in the growing algae and the potential it has for production of oil that can be used for transportation fuel, especially since using algae eliminates the problem associated with converting crop foods to fuel.”

The use of algae for multiple applications has several appeals, including:

• Algal oil is very similar to other vegetable oils, but its yield is projected at 100 times that of soybean per acre of land on an annual basis.

• Unlike other plants, algae reproduce quickly without roots and stems, and they never go dormant.

• Algae can remove carbon dioxide from power plant emissions and recover nutrients from wastewater.

According to Hu, the technology to help algae reproduce effectively is still five years away.

“The critical issue is the biomass feedstock, not oil conversion,” Hu says. “To bring the cost down we need much more breakthroughs and innovations. Bioreactors are expensive at this stage. We need a cost-efficient way to sustain high growth.”

Once algae reach a critical mass, traditional methods can be used to extract oil from the plants. In turn, these oils can be refined into gasoline, biopolymers and jet fuel.

So what’s next in the process of making jet fuel from algae?

“Our effort will be geared to developing a pilot-scale facility that will enable us to integrate various components of oil production and evaluate the economics of the process,” Sommerfeld says. “Since ASU is a leader in developing approaches to sustainability, it could, for example, incorporate the use of algae-produced biofuels on some of its vehicles over the next several years as our production increases.”

Hu and Sommerfeld are the co-directors of the Laboratory for Algae Research & Biotechnology (LARB) at the Polytechnic campus.

The duo has been able to take their combined 40-plus years of research with algae and apply it to use in air and water remediation, alternative fuels and animal feed. Considered a nuisance by many, algae have the potential to someday become an environmentally sound substitute for crude oil.

Students, teachers participate in bioscience program

lccampb — Fri, 08 Aug 2008 17:48:44 -0600

While many of their peers were off enjoying summer vacations, 58 talented and dedicated Valley high school students and teachers engaged in solving real-world problems alongside Biodesign Institute scientists as part of Arizona’s largest high school bioscience internship program at ASU.

Twenty-four high schools in 14 districts with existing or emerging biotechnology programs were invited to send a teacher to participate in the internship program. The teachers, in turn, helped select students for the paid six-week internship. Among the participating teachers were three from the Teach For America initiative, the nation’s largest provider of teachers for low-income communities.

Now in its third year, the Biodesign Institute High School Internship program’s expanded scope was made possible through a $50,000 grant from the ASU Foundation’s Women and Philanthropy program.

“By including teachers for the first time in our internship program, we are helping them introduce more students to potential bioscience careers than ever before, with a potential impact on more than 4,000 Arizona high school students in the coming academic year,” says Richard Fisher, the Biodesign Institute’s director of educational outreach. “The timing couldn’t have been better. As more Arizona high schools develop biotechnology programs, teachers can use their Biodesign experience to bolster their expertise and curriculum development.”

“Introducing science concepts to students this early will reap a lot of rewards for building a brain-based industry like biotechnology,” says Ben Perodeau, a biology teacher from Tolleson Union’s University High School.

Each student-teacher team worked on a research project tackling a pressing societal problem, ranging from decontamination of groundwater to building nanostructures for diagnostics or working on cures for infectious diseases and cancer. Perodeau and his student partner, upcoming junior Dulce Gomez, spent their internship with a Biodesign research team that is developing a vaccine against the disease tularemia, which is a potential biothreat against which no effective vaccine exists.

The challenging work is motivating 16-year-old Gomez to take a 90-minute bus ride to and from Tolleson each day.

“I’ve always loved science, although sometimes the work can be a little difficult to explain to my parents,” she says.

Each student-teacher pair was mentored by a Biodesign Insititute researcher who supervised their day-to-day progress.

The daily exposure to the large research teams and world-class facilities of the institute gave the interns an in-depth introduction to the career of a research scientist.

Biology teacher Michelle Landreville from the Mesa High School Biotech Academy marveled at the pace of innovation and discovery.

“We didn’t even extract DNA when I was in college, so this is all new to me,” Landreville says. “The Biodesign Institute is a very stimulating environment where everyone encourages you to think out of the box.”

For upcoming senior Jennifer Lino of La Joya Community High School, the opportunity to investigate the causes of esophageal cancer had a very special, personal motivation. “My father had throat surgery (for cancer) when I was a little kid,” she says. “Now he breathes through a tube in his throat. I hope that, someday, nobody else will have to go through his struggle.”

Julie Kurth, julie.kurth@asu.edu
(480) 727-9386
Biodesign Institute

ASU researchers use salmonella to administer vaccines

cderra — Tue, 08 Jul 2008 13:59:27 -0600

Researchers at the Biodesign Institute at Arizona State University have made a major step forward in their work to develop a biologically engineered organism that can effectively deliver an antigen in the body. The researchers report that they have been able to use live salmonella bacterium as the containment/delivery method for an antigen.

The work is a major step forward in development of a new means of biological containment that would be a key component to a new way to deliver vaccines in animals and humans. If fully developed, the new method could be used to administer vaccines to many of those who do not benefit from traditional vaccines because of their cost, because of drug resistance or because of limited effects on children.

Outlined in the paper, “Regulated programmed lysis of recombinant Salmonella in host tissues to release protective antigens and confer biological containment,” published on the online version (July 7) of the Proceedings of the National Academy of Sciences, the researchers describe a new, novel and effective means of biological containment for antigen delivery. The method not only effectively delivers the antigen in the body, but does so in a way that does not infect the body with salmonella and does not leave any vaccine cells in the environment.

The research team includes scientists formerly at Washington University, St. Louis, and Megan Health Inc., St. Louis, as well as those at ASU’s Biodesign Institute and the School of Life Sciences.

“Our goal is to design, engineer and evaluate a live bacterial (using salmonella) antigen delivery system that would display regulated delayed lysis in vivo after invasion into and colonizing internal lymphoid tissues in an immunized individual,” said Roy Curtiss, director of the Center for Infectious Diseases and Vaccinology at the Biodesign Institute and a professor in ASU’s School of Life Sciences. Curtiss was part of the research team that made the discovery.

“We wanted to do this in a way so that no disease symptoms due to salmonella would arise, a protective immune response would be induced to the pathogen whose protective antigen was delivered by the vaccine construction (in this case against S. pneumoniae due to an immune response to PspA), and there would be no ability for live bacterial vaccine cells to either persist in vivo or to survive if shed into the environment,” Curtiss added.

“The biological containment system we developed is sufficient by itself on conferring attenuation, the inability to cause disease symptoms, and ability to deliver an antigen to induce protective immunity,” Curtiss said. “We have high expectations that this delivery system will be safe and effective when administered to animals and humans.”

A key to the project, according to Curtiss, is “turning a foe into a friend.” That foe is the salmonella bacterium—the leading cause of human food-borne illness and which is currently in the news due to contaminated tomatoes and other food crops. Curtiss’ team, through genetic know-how, has developed a variety of ways to tame salmonella in the lab and use it as a delivery vector for vaccines.

“We try to genetically modify the salmonella bacterium to eliminate its harmful effects -- the diarrhea, gut inflammation and fluid secretion -- while keeping the wherewithal to induce immunity against the bacteria causing pneumonia or other infectious diseases,” Curtiss said. Several in his research team attack the problem from different angles, with some focusing on weakening salmonella, others boosting the immune response and others optimizing the self-destruct mechanism.

Speaking about the application of a pneumonia antigen, team leader Wei Kong, of the Biodesign Institute, said: “If we tried to use live Streptococcus pneumoniae causing pneumonia for a vaccine, we would obviously kill the patient. The benefit of a live vaccine that uses a weakened form of salmonella, is that the salmonella can be taken up through the intestinal lining and stimulate an immune response by using just a portion of the bacteria causing pneumonia that itself is not deadly.”

In experiments, the genetically modified Salmonella enterica bacterium colonizes the lymph tissues of the host and manufactures a protein from the S. pneumoniae bacterium, which then triggers a strong antibody response. Unlike most vaccines that are entirely manufactured by a vaccine company, the attenuated recombinant salmonella vaccine after entry into the immunized individual serves as its own factory to produce (manufacture) the protective antigens (proteins) from the S. pneumoniae pathogen. This ability to cause manufacture in the immunized individual dramatically decreases the cost of such vaccines to make them affordable for use in the developing world, Curtiss said.

An important factor for the research team was to genetically program the S. enterica bacterium to destroy itself so that it is not released into the environment, Curtiss said.

“Biological containment systems are important to address the potential risk posed by any unintentional release of the modified salmonella into the environment,” he explained. The salmonella life cycle is balanced to allow enough time to enter the body and build an immune response, while leading to cell death by bursting the cells and preventing the vaccine strain from spreading into the environment.

“The data show that the system we have devised results in cell lysis in the absence of arabinose and clearance of the strain from host tissues,” the researchers state in the PNAS article.

“More importantly, our strain was fully capable of delivering a test antigen and inducing a robust immune response comparable to that of a vaccine strain without this containment system, thereby demonstrating that this system has all of the features required for biological containment of a recombinant attenuated salmonella vaccine,” they added.

The research was funded by the U.S. Department of Agriculture and the National Institutes of Health.

Rittmann offers fresh insight on energy challenge

jcasper — Wed, 02 Jul 2008 16:03:16 -0600

Biodesign Institute researcher touts bioenergy alternatives

Perhaps there is no greater societal need for scientific know-how than in finding new ways to meet future energy demands. Skyrocketing gas prices, an uncertain oil supply, increasing demand from around the world, and the looming threat of climate change have made identifying and developing realistic energy alternatives a national priority.

For Biodesign Institute researcher Bruce Rittmann, the threat of global warming also presents a significant opportunity for innovation and fresh solutions to today’s energy challenges.

“Beginning with the Industrial Revolution, the unprecedented expansions of human population and economic activity have been based on combusting fossil fuels,” Rittmann says. “Today, fossil fuels provide 80 percent of the energy needs to run human society worldwide: 34 percent petroleum, 32 percent coal and 14 percent natural gas.”

In a new “Perspective” article published in the journal Biotechnology and Bioengineering, Rittmann points the way toward developing bioenergy as the best realistic alternative to meet our current and future energy needs while cutting back on the use of fossil fuels.

Rittmann directs the Center for Environmental Biotechnology and is a professor in the Ira A. Fulton School of Engineering’s Department of Civil and Environmental Engineering.

“The only way that human society has a realistic way of slowing and reversing global warming is bioenergy – and it has to be bioenergy that is done right,” says Rittmann, who leads many of Biodesign’s sustainability-themed research projects. “Most critically, we need to be able to have bioenergy sources that work on a very, very large scale.”

Besides the scalability issues of bioenergy, any technologies developed also must be able to produce energy while minimizing damage to the environment or affecting the world’s food supply.

For Rittmann, the most obvious renewable-energy solution – one that passes the tests of scalability, environment and food – stems from the very factor that makes life on Earth possible: sunlight.

“The good news is that we have plenty of energy from the sun,” Rittmann says. “Every day, the sun sends to the earth’s surface about 173,000 terawatts of energy, or more than 10,000 times more that is used by human society. So, we have a lot of what we like to call ‘upside potential’ for capturing sunlight energy.”

Up to now, harnessing the energy of the sun has proven to be technically and socially challenging. In particular, approaches to make biofuels from crops such as corn have been met with skepticism in recent days.

“When people think of capturing sunlight energy in biomass, they focus on plants, which are familiar,” Rittmann says. “However, plants are quite inefficient at capturing sunlight energy and turning it into biomass that can be used a fuel.”

As a result, he says, plants could provide only a tiny fraction of our society’s energy needs.

“Obviously, we need the plants for producing food and sustaining natural ecosystems,” Rittmann says. “Plants simply fail the scalability, environmental and food tests.”

In contrast, microorganisms – the smallest forms of life on Earth – can meet the scalability and environmental tests. Rittmann sees a vast untapped potential of using microbes in service to society to meet our energy challenges.

“Photosynthetic bacteria can capture sunlight energy at rates 100 times or more greater than plants, and they do not compete for arable land,” Rittmann says, adding that this high rate of energy capture means that renewable biofuels can be generated in quantities that rival our current use of fossil fuels.

In addition, non-photosynthetic microorganisms are capable of converting the energy value of all kinds of biomass, including wastes, into readily useful energy forms, such as methane, hydrogen and electricity.

“Microorganisms can provide just the services our society needs to move from fossil fuels to renewable biofuels,” Rittmann says. “Only the microorganisms can pass all the tests, and we should take full advantage of the opportunities that microorganisms present.”

Biodesign Institute adds 2 outreach educators

lccampb — Wed, 02 Jul 2008 13:21:05 -0600

The Biodesign Institute at ASU has appointed Kenneth Costenson and Lisa Osinga as outreach educators. Together, they bring more than 35 years of teaching and educational administrative experience to the institute.

Costenson and Osinga will develop tactile and experiential science-based education for teachers and students in grades K-6, and will seek outside funding to support these programs.

“Ken and Lisa have expertise in delivering science curriculum that engages students that will be a great asset in our efforts to inspire the next generation of scientists,” says Richard Fisher, director of education outreach for Biodesign.

Costensen, a seasoned educator, most recently served as secondary science specialist for the Mesa Public Schools, where he coordinated the delivery of the science curriculum for the junior and senior high schools throughout the district. He supervised and was instrumental in establishing the Mesa Biotech Academy at Mesa High School, which has become a national model for secondary biotechnology programs.

Costenson started working with students in 1969 in Davenport, Iowa. He has inspired students through his 19 years as a teacher at Dobson High School in Mesa and prior teaching roles in Illinois and Texas. Since moving to the Phoenix area, Costenson also served as an adjunct instructor at Rio Salado Community College in Tempe, and at ASU’s Tempe and Polytechnic campuses.

He earned a bachelor’s degree in biology and a master’s degree in zoology from the Western Illinois University-Macomb.

Osinga brings a fresh classroom perspective to the position of outreach educator. Before her current position, Osinga was a biology teacher at Thunderbird High School in Phoenix. There, she taught accelerated biology and general biology courses.

Since 2006, Osinga has been part of Promoting Reform through Instructional Materials that Educate (PRIME), a program that facilitates the selection of quality teaching materials, which align with Arizona science standards. In fact, she completed Project PRIME’s graduate-level program at Northern Arizona University.

Osinga earned a bachelor’s degree in biology and a master’s degree in secondary education from ASU.

Julie Kurth, julie.kurth@asu.edu
(480) 727-9386
Biodesign Institute

Study examines link between gut bacteria, obesity

jcasper — Fri, 13 Jun 2008 12:34:38 -0600

Obesity is more than a cosmetic concern, because it increases a person’s risk for developing high blood pressure, diabetes and many other serious health problems. It’s well-understood that consuming more calories than you expend through exercise and daily activities causes weight gain. But with about one in every three American adults now considered obese, researchers are attempting to identify additional factors that affect a person’s tendency to gain and retain excess weight.

In the April issue of Mayo Clinic Proceedings, researchers from Mayo Clinic Arizona and the Biodesign Institute at ASU examine the role that bacteria found in the human gastrointestinal tract play in regulating weight and the development of obesity.

Known as gut microbiota, the trillions of bacteria that populate the human gastrointestinal tract perform a variety of chores. These “friendly” microbes help extract calories from what we eat, help store these calories for later use, and provide energy and nutrients for the production of new bacteria to continue this work.

According to John DiBaise, a Mayo Clinic Arizona gastroenterologist and lead author of the Mayo Clinic Proceedings article, several animal studies suggest that gut microbiota are involved in regulating weight and that modifying these bacteria could one day be a treatment option for obesity. Other authors of the article include Husen Zhang, Rosa Krajmalnik-Brown and Bruce E. Rittmann of the Biodesign Institute’s Center for Environmental Biotechnology; and Mayo Clinic Arizona researchers Michael Crowell and G. Anton Decker.

One study cited by the authors observed that young, conventionally reared mice have a significantly higher body fat content than a laboratory-bred, germ-free strain of mice that lack these bacteria, even though they consumed less food than their germ-free counterparts.

When the same research group transplanted gut microbiota from normal mice into germ-free mice, the germ-free mice experienced a 60 percent increase in body fat within two weeks, without any increase in food consumption or obvious differences in energy expenditure.

The study was the result of a unique collaboration between physicians at Mayo Clinic and environmental remediation experts at the Biodesign Institute, made possible by seed funding provided by the Mayo Clinic to pursue innovative solutions to leading problems affecting human health.

“In environmental biotechnology, we manage microbial communities, usually to improve environmental quality,” says Rittmann, who directs the institute’s Center for Environmental Biotechnology and is a leading expert in microbial remediation. “The idea to improve human health directly by managing the microorganisms in us is an exciting new path for us, and a wonderful collaboration between medical and environmental scientists.”

Another study reviewed by the authors focused on the gene content of the gut microbiota in mice. Finding more end products of fermentation and fewer calories in the feces from obese mice led researchers to speculate that the gut microbiota in the obese mice help extract additional calories from ingested food.

Although information on the link between gut microbiota and obesity in human subjects is more limited, the authors also present some evidence supporting this connection. One study cited placed 12 obese participants in a weight-loss program for a year, randomly assigning them to either a fat-restricted or carbohydrate-restricted low-calorie diet. Researchers noted distinct differences between lean and obese participants when they monitored the type and number of bacteria found in participants’ stool samples before and after the diet changes.

Another study cited followed children from birth to age 7 and analyzed stool samples for the presence of bacteria collected at ages 6 months and 12 months. The children who were normal weight at age 7 had distinctly different bacteria in their samples than those collected from overweight-obese children, suggesting that differences in the composition of the gut microbiota precede overweight-obesity.

The research team acknowledges that much more research is needed to clarify a number of issues related to the relationship between the gut microbiota and obesity. Future studies need to establish whether the small changes in caloric extraction seen in recent studies can produce measurable weight differences in humans. Second, researchers need to prove or disprove the possible relationship between the gut microbiota and the regulation of weight.

Finally, the authors note that the next wave of research should explore the safety and feasibility of modifying the gut microbiota in clinical trials involving humans.

Researchers synthesize molecule that exhibits self-control

cderra — Tue, 10 Jun 2008 17:44:08 -0600

Plants have an ambivalent relationship with light. They need it to live, but too much light leads to the increased production of high-energy chemical intermediates that can injure or kill the plant.

The intermediates do this because the efficient conversion of sunlight into chemical energy cannot keep up with sunlight streaming into the plant.

“The intermediates don’t have anywhere to go because the system is jammed up down the line,” says ASU chemist Devens Gust.
Plants employ a sophisticated process to defend against damage.

To better understand this process, Gust, along with fellow ASU researchers Thomas Moore and Ana Moore, both professors of chemistry and biochemistry, designed a molecule that mimics what happens in nature. They reported results with their molecule in the advanced online publication of Nature Nanotechnology (May 4).

In nature, plants defend against this sunlight overload process using non-photochemical quenching (NPQ). This process drains off the excess light excitation energy as heat so that it cannot generate the destructive high-energy species.

The ASU-designed molecule works in a similar fashion, in that it converts absorbed light to electrochemical energy but reduces the efficiency of the conversion as light intensity increases. The ASU-designed molecule has several components, including two light-gathering antennas: a porphyrin electron donor, a fullerene acceptor and a control unit that reversibly photoisomerizes between a dihydroindolizine (DHI) and a betaine (BT).

When white light (sunlight) shines on a solution of the molecules, light absorbed by the porphyrin (or by the antennas) is converted to electrochemical potential energy. When the white light intensity is increased, the DHI on some molecules change to a different molecular structure, BT, that drains light excitation energy out of the porphyrin and converts it to heat, avoiding the generation of excess electrochemical potential.

As the light becomes brighter, more molecules switch to the non-functional form, so that the conversion of light to chemical energy becomes less efficient. The molecule adapts to its environment, regulating its behavior in response to the light intensity.

“One hallmark of living cells is their ability to sense and respond to surrounding conditions,” Thomas Moore says. “In the case of metabolic control, this process involves molecular-level recognition events that are translated into control of a chemical process.

“Functionally, this mimics one of the processes in photosynthesis that severely limits the energy conversion efficiency of higher plants. One way in which this work is important is that, by understanding these events at the molecular level, one can imagine redesigning photosynthesis to improve energy conversion efficiency – and, thereby, come closer to meeting our energy needs.”

The research also is important to one aspect of the exploding field of nanotechnology, that of regulation, Gust says. Biological systems are known for their ability to engage in adaptive self-regulation. The nanoscale components respond to other nanoscale systems, and to external stimuli, to keep everything in balance and functioning properly. The ASU research shows how a bio-regulation system has been captured in a non-biological molecular scale analog process.

“Achieving such behavior in human-made devices is vital if we are to realize the promise of nanotechnology,” Gust says. “Although the mechanism of control used in the ASU molecule is different from that employed in NPQ, the overall effect is the same as occurs in the natural photosynthetic process.”

In addition to Gust, Thomas Moore and Ana Moore, the ASU work was carried out by Stephen Straight, Gerdenis Kodis, Yuichi Terazono and Michael Hambourger.

Jenny Green, jenny.green@asu.edu
(480) 727-6243
Department of Chemistry and Biochemistry

Personalized medicine initiative targets lung cancer

jcasper — Tue, 10 Jun 2008 16:32:57 -0600

A U.S.-based personalized medicine initiative led by scientists from the Biodesign Institute, Translational Genomics Research Institute (TGen) and Seattle’s Fred Hutchinson Cancer Research Center has secured its first major international collaboration with the government of Luxembourg.

The Partnership for Personalized Medicine, formed last fall with funding support from the Virgina G. Piper Charitable Trust and Flinn Foundation, will explore the development of novel diagnostics for lung cancer.

The goal of the Luxembourg lung cancer project is to advance research in personalized medicine by pursuing research projects to develop molecular diagnostics for specific diseases. These research projects center on the selection and validation of biomarkers to more effectively diagnose and manage disease from early detection through therapeutic follow-up.

“The focus on lung cancer came to the forefront of our efforts because it is currently the leading malignancy,” says George Poste, director of the Biodesign Institute. “To make the greatest impact, it is imperative that we find diagnostic markers that can more accurately predict the success of treatment regimens for improved patient care and outcomes.”

Poste notes that lung cancers are notoriously difficult to treat, with most patients failing to respond to their first therapeutic regimen, resulting in highly expensive ($40,000-100,000 each) treatments with an initial success that can be as low as one out of every 10 patients – and, in best-case scenarios, 40 percent.

The Luxembourg project will focus specifically on lung cancer, for which there are no reliable tools for early detection, and for patients with advanced disease with virtually no known cures.

The project also will seek to demonstrate that earlier detection and intervention can reduce health care costs. The initiative capitalizes on the efforts of the U.S.-based Partnership for Personalized Medicine (PPM), led by Fred Hutchinson Cancer Center director and Nobel laureate Lee Hartwell, and will develop use of new personalized, protein-based diagnostic tools.

“This is a tremendous first step, and it’s exactly the right kind of project,” says ASU President Michael Crow.

Crow says he believes that, if the project succeeds, it is a formula that can be repeated for other diseases, and an important demonstration of the type of “leapfrog strategy” that can help Arizona establish itself in the 21st century economy.

The cornerstone of the partnership is the creation of the Virginia G. Piper Center for Personalized Diagnostics that draws upon the scientific strengths of the state’s leading bioscience entities: the Biodesign Institute and TGen.

Biodesign’s role will primary focus on using state-of-the-art instrumentation such as mass spectrometry and bioinformatics approaches to analyze novel proteins expressed in lung cancer. The emphasis on identifying peptides and proteins that could be detectible in the blood stream will allow for earlier detection of this devastating disease.

In addition, identification of abnormal peptides may aid other cross-collaborative institutional efforts such as identifying potential immunization antigens for use in Biodesign colleague Stephen Johnston’s cancer vaccine project. Last year, Johnston received a $7 million award from the Department of Defense to develop a prophylatic cancer vaccine in collaboration with Mayo Clinic Arizona.

The lung cancer initiative was part of the government of the Grand Duchy of Luxembourg’s ambitious plan to increase the pace of innovation based on cutting-edge research in the areas of molecular biology, systems biology and personalized medicine.

This plan will include formation of a centralized biobank/tissue repository, two major projects to further research in the field of molecular biology, which is the cornerstone of personalized medicine, and a project to demonstrate the effectiveness of new diagnostics tests for earlier detection and treatment of lung cancer.

The collaboration consists of interrelated research initiatives that build on each other. They include the Partnership for Personalized Medicine (PPM) led by Leland H. Hartwell, director, Nobel Laureate in Physiology or Medicine in 2001 and president of the Fred Hutchinson Cancer Research Center in Seattle, Washington; the Institute for Systems Biology (ISB), also in Seattle, led by Leroy Hood, president of ISB and co-founder of U.S.-based Amgen Inc.; ASU’s Biodesign Institute, led by Poste; and the Translational Genomics Research Institute (TGen), led by Jeffrey Trent, president and scientific director of TGen and former scientific director at the National Human Genome Research Institute of the National Institutes of Health.

The public-private initiative is expected to serve as a model for other international collaborations among partners looking to share research and development costs and to gain access to each other’s information, networks and markets.

The Luxembourg collaboration was developed and negotiated in consultation with the global professional services organization, PricewaterhouseCoopers, and is built on an integrated approach that links research, education, health care and the economy.

“We thank the foresight and leadership demonstrated by the Luxembourg government,” Poste says. “This model may serve as a driving force of innovation for the European Union, as well as U.S. health care.”

The announcement was made jointly by three branches of Luxembourg’s government: the Ministry of the Economy and Foreign Trade, the Ministry for Culture, Higher Education and Research, and the Ministry of Health.

The Luxembourg government is investing $200 million in the initiative, with the hope that ultimately it will improve the health of its own people by increasing the ability to administer the right drug to the right patient at the right time and in the right dose. In addition, it seeks to accelerate the global pace and integration of biomedical research, education and commercial development around the world.