Iowa State University

BCB Faculty member, and GDCB Associate Professor, Hui-Hsien Chou, receives a $1.6m sponsored research award from NSF

Dr. Hui-Hsien Chou, Associate Professor of Genetics, Development and Cell Biology and Computer Science, was awarded a National Science Foundation (NSF) grant for his research project entitled "Optimal siRNA Design Based on Whole Genome Thermodynamic Analysis" to start in September 2009. This continuing grant, with a total of $1,595,295 for up to four years, will be used to develop novel small interference RNA (siRNA) design software.   RNA interference (RNAi) is a natural phenomenon in cells where siRNAs guide the recognition, inhibition and potential degradation of target messenger RNAs (mRNA), resulting in the loss of their gene functions. RNAi is an important molecular biology technology that can be used to perform functional genomic studies. It is also suggested that siRNAs can be used as drugs to stop oncogenes in cancer cells or to fight off viruses.

The two main goals of this project are to create novel siRNA design software that can select high quality, gene-specific siRNAs based on the comprehensive thermodynamic analysis of an entire genome and to validate the quality of the designed siRNAs with RNAi experiments. The software developed under this project will be made available from the Complex Computation Lab website at Iowa State University http://www.complex.iastate.edu

Petascale Computing in 2011 -- Srinivas Aluru represents Iowa State in Blue Waters Consortium

Blue Waters is expected to be the most powerful supercomputer available for open scientific research when it comes online in 2011. The project includes the NCSA, the University of Illinois, IBM and the Great Lakes Consortium. Iowa State is one of the consortium's founding members. Srinivas Aluru serves as the consortium board member representing Iowa State.

A key element of the Blue Waters project, the consortium of universities, colleges, national research laboratories and other institutions is designed to foster use of petascale computing, among other things through development of new software, applications and technologies. The group's educational and workforce development program is aimed at making sure advances are passed to the next generation of researchers and applied to frontier questions in science, technology, engineering and the social sciences. more

The USDA Funds Dr. Honavar and Dr. Tuggle's Research on Elucidating Gene Networks Involved in Immune Response to Viral Infections

The resulting tools from this research effort will be applicable to a broad range of problems in identifying and characterizing gene networks that orchestrate important biological functions. This project will help advance additional collaborations involving researchers from the Center for Computational Intelligence, Learning, and Discovery (www.cild.iastate.edu) and the Center for Integrated Animal Genomics (www.ciag.iastate.edu) at Iowa State University to further identify and characterize the role of gene networks in biological functions.

Interdisciplinary Research Continues to Grow at ISU --

First year of Center for Biorenewable Chemicals builds bridges to science, industry

by Mike Krapfl, ISU News Service, Sept. 18, 2009 --

AMES, Iowa - Brent Shanks studies chemical catalysts in Iowa State University's Sweeney Hall. Just a few buildings to the north, Basil Nikolau, BCB Faculty member and Professor in the Biochemistry, Biophysics and Molecular Biology Department, studies biological catalysts.

Nikolau said the two researchers used to talk twice a year about the science of using different kinds of catalysts to accelerate chemical reactions. But now, thanks to the NSF Engineering Research Center for Biorenewable Chemicals based at Iowa State, they're meeting 20-plus times a year to talk catalysis. That's just one way the center is beginning to bring together two research camps that haven't been working together.

And that's a small example of the progress the center has sparked in the year since it was established by a five-year, $18.5 million grant from the National Science Foundation (NSF).

The center - by getting researchers to work together, teaching students to cross disciplines, bringing industry into the research and developing collaborations overseas - is working toward its goal of transforming the ways industrial chemicals are produced. Rather than an industry based on petroleum, center researchers want to see an industry based on biorenewable resources.

Shanks, the director of the Center for Biorenewable Chemicals and professor of chemical and biological engineering, and Nikolau, the center's deputy director and the Frances M. Craig Professor in the departments of biochemistry, biophysics and molecular biology and food science and human nutrition, said the center has made good progress in its first year.

It has passed an NSF evaluation. It has assembled a team of 24 researchers from nine academic institutions who are working with 70 graduate students and post-doctoral researchers and more than 20 undergraduate students. It is working with 14 high school and middle school teachers. It has signed on five industrial partners and is working with the Iowa Department of Economic Development to bring in more. It has ties to six scientific journal publications, including "Catalytic Conversion of Biomass to Monofunctional Hydrocarbons and Targeted Liquid-Fuel Classes," published by Science in October 2008.

Shanks said a highlight of the center's work so far has been watching all of that come together: "I can now see the pieces taking shape for what's required to make this center successful."

For Nikolau, the highlight was watching meeting rooms fill during the NSF's annual site visit in May: "I was pleased that by May the center had grown by so many people."

All those people are involved in the center's core mission: to find ways to integrate biological and chemical catalysts to produce biorenewable chemicals. Advances could move the $400 billion U.S. industrial chemical industry toward more sustainable feedstocks and technologies.

And Shanks thinks Iowa State is in a unique position to research and develop those advancements.

First, Shanks said, Iowa's farms are a tremendous source of biomass. And second, Iowa State has developed scientific expertise in biorenewable technologies and plant sciences.

"We have the biomass and the technical expertise here," he said. "Those are some of the pieces that make our center unique."

But can the center actually help transform the chemical industry?

"Just by the fact we have a broad vision to use both chemical and biological catalysts to attack this problem is something that's been missing," Shanks said. "The industry has been developing biorenewable technologies product by product. Pulling these ideas together into a general framework for creating a range of chemicals is a big part of the battle."

And, Nikolau said, "The other way we'll transform this industry is through our students. They'll take the training they receive from the center out into industry."

The NSF Engineering Research Center for Biorenewable Chemicals is based at Iowa State and is working with academic partners at the University of New Mexico in Albuquerque, Rice University in Houston, the University of Wisconsin-Madison, the University of Virginia in Charlottesville and the University of California, Irvine. The center is also working with affiliated faculty from the University of Michigan in Ann Arbor and the Salk Institute for Biological Studies in San Diego. International partners are the Fritz-Haber-Institute of the Max-Planck-Society in Berlin, Germany, and the Technical University of Denmark in Lyngby. The center is also developing pre-college programs with Des Moines Public Schools and the Heartland Area Education Agency in Johnston. The center has industrial partnerships with the Grain Processing Corp. of Muscatine; the Chevron Phillips Chemical Co. of The Woodlands, Texas; POET of Sioux Falls, S.D.; Novozymes of Denmark (with an office in the Iowa State University Research Park); and Elevance Renewable Sciences Inc. of Bolingbrook, Ill. The center will develop additional partnerships with industry and start-up companies through Iowa State's Pappajohn Center for Entrepreneurship and venture capital firms Khosla Ventures and Kleiner Perkins Caufield & Byers.

Iowa State researchers looking for catalyst that allows plants to produce hydrocarbons

But, she said, researchers don't know the exact structures, mechanisms, genetics and metabolism of that conversion.

Shanks and a team of researchers recently won a four-year, $2 million grant from the National Science Foundation's Office of Emerging Frontiers in Research and Innovation to study the production of biological hydrocarbons.

The research team includes BCB Faculty member, Basil Nikolau, Iowa State's Frances M. Craig Professor in the departments of biochemistry, biophysics and molecular biology and food science and human nutrition, who's also the deputy director of the NSF Engineering Research Center for Biorenewable Chemicals based at Iowa State; Tom Bobik, an ISU associate professor of BBMB and 2 faculty at other institutes.

The project will also support the research, training and education of a number of post-doctoral researchers, graduate students and undergraduate students at Iowa State and the other universities. And it will provide these young researchers with an opportunity to broaden their training experience with national and international collaborations.

Shanks said the researchers' specific task is to isolate, characterize and bioengineer a catalyst that creates the biological hydrocarbons.

Nikolau said the current project will not address which plants or algae are the best producers of biological hydrocarbons or how the biological process can best be exploited. He said those studies would build on the discoveries of the current project.

But can plants directly produce hydrocarbons for biofuels? Is that too good to be true? Shanks said the research could lead to technologies that transform how liquid fuels are produced. And that's the kind of project the science foundation's Office of Emerging Frontiers in Research and Innovation is supporting.

According to the foundation, the office's goal is to support "transformative opportunities potentially leading to: new research areas …; new industries or capabilities that result in a leadership position for the country; and/or significant progress on a recognized national need or grand challenge."

A new, sustainable source of hydrocarbons could lead to all of that: "The production of renewable hydrocarbons that would integrate directly into the existing fossil-carbon infrastructure would represent an important advance in biofuels technology," the researchers wrote in their project proposal. "Transforming this existing industry to a bio-based carbon feed-source is a grand challenge that will need to integrate unique and proficient biological solutions with new engineering efficiencies."

William D. Beavis named interim director of the Plant Sciences Institute at Iowa State University

AMES, Iowa - by Kan Kuester, ISU News Service - William D. Beavis, George F. Sprague Endowed Chair and professor in the department of agronomy has been named interim director for the Plant Sciences Institute (PSI) at Iowa State University, effective Sept. 15, 2009. Beavis is a BCB Faculty member at Iowa State.

Prior to joining Iowa State as a faculty member in August, 2007, Beavis was chief scientific officer for the National Center for Genome Resources, in Santa Fe, NM. In this role, Beavis developed and implemented the strategic and tactical vision for this sustainable non-profit research institute, experience he will now apply to advance the PSI.

Stephen Howell, the institute's director for nearly nine years, steps down this month to become the new Director of the Division of Molecular and Cellular Biosciences at the National Science Foundation in Washington, D.C.

"I am delighted that we were able to recruit such an accomplished scientist and experienced administrator to serve as interim while we conduct the search for a new director," said Sharron Quisenberry, vice president for research and economic development.

Beavis earned a bachelor's degree in range management from Humboldt State University and an interdisciplinary master's degree in biology and statistics from New Mexico State University. He received a doctorate in plant breeding from Iowa State in 1985.

Beavis was a research statistician at Pioneer Hi-Bred International from 1986 to1998, gaining extensive experience in the application of statistical genetic methods. While at Pioneer, Beavis worked on optimization of biotechnologies and became widely recognized for development of statistical methods for identification of quantitative trait loci. The latter efforts resulted in recognition that genetic effects are overestimated when evaluating genomic regions with small sample sizes of segregating families. This general result has become known as "the Beavis Effect."

The Plant Sciences Institute is dedicated to advancing fundamental discoveries of plant systems and new molecular technologies that support a sustainable biobased future. Institute researchers are Iowa State faculty, whose research efforts help feed a growing world population, strengthen human health and nutrition, improve crop quality and yield, foster environmental sustainability and expand the uses of plants for biobased products and bioenergy. The Institute supports the training of students and promotes new technologies to aid in the economic development of agricultural industries throughout Iowa. The Institute is supported through public and private funding.

BCB Faculty member and GDCB Professor, Drena Dobbs, receives sponsored funding from NSF

Dr. Drena Dobbs, Professor of GDCB; Dr. Daniel Voytas, collaborating faculty in GDCB and Director of the Beckman Center at the University of Minnesota; and Dr. J. Keith Joung, Professor at Harvard Medical School; have been awarded $3,365,001 by the National Science Foundation for their collaborative research project entitled “NSF TRPGR: Precise Engineering of Plant Genomes using Zinc Finger Nucleases.” Dr. Kan Wang, Professor of Agronomy and Director of ISU's Plant Transformation Facility is coPI on the ISU sub-contract award of $916,295.   The newly funded project will develop improved methodologies to enable genomics scientists to readily target and modify specific genes in plants and other organisms, including human. In collaboration with the Zinc Finger Consortium http://www.zincfingers.org/, the team has generated efficient platforms and computational resources for zinc finger protein (ZFP) engineering.

At ISU, the Dobbs group will generate improved computational tools that reduce the time and expense required to design ZFPs and choose target sites that function successfully in vivo; the Wang group will develop improved protocols for gene targeting in rice, allowing researchers to better exploit the many genetic resources available for this model crop. Graduate research assistantships and seed funding for preliminary experiments that contributed to the success of the NSF proposal were provided by GDCB, BCB and CIAG at ISU, and an MGET training grant from the USDA.

August 2009: GDCB Professor Don Sakaguchi receives sponsored funding award from the NIH

Iowa State faculty attract $7.7 million in American Recovery and Reinvestment Act grants

Iowa State University researchers have so far won 19 grants worth a total of $7.7 million from federal agencies awarding money from the American Recovery and Reinvestment Act.

The grants range from $2 million for a study of a bio-engineering technology that could produce biological hydrocarbons for biofuels to $600,000 for a study of cell membranes to $51,710 for a study of how the Ebola virus can inhibit a body's antiviral response. Fifteen of the grants are from the National Science Foundation and four are from the National Institutes of Health.

"These competitive grants are another example of Iowa State researchers leveraging the university's strengths in science and technology," said Sharron Quisenberry, Iowa State's vice president for research and economic development. "These grants will allow Iowa State researchers to build their research programs, work with more students and advance their projects. The ultimate benefit will be to advance our knowledge and, ultimately, to provide for the well-being of people in Iowa as we build a better future."

The recovery and reinvestment act provided the National Institutes of Health with $8.2 billion and the National Science Foundation with $3 billion to help stimulate the country's economy by supporting scientific research.

Arden L. Bement Jr., the director of the National Science Foundation, said the funding is "sorely needed to ensure that America remains a leader in science and engineering research and education."

The following BCB Faculty members at Iowa State received grants supported by the American Recovery and Reinvestment Act:

August 2009: GDCB Professor Thomas Peterson receives sponsored award from NSF

This project research will provide significant new insight into the role of transposable elements in generating duplications, and the impact these duplications have on genetic recombination and gene expression. Research results may lead to significant advances in breeding of crop plants, which will improve agricultural efficiency and environmental sustainability.

ISU's Outstanding Achievement in Departmental Leadership Award to Jonathan Wendel, EEOB

BCB Faculty Member, and Chair of EEOB, Jonathan Wendel recently received ISU's Outstanding Achievement in Departmental Leadership Award which recognizes department chairs who have demonstrated exceptional leadership qualities in advancing the faculty, staff, students and programs in their departments:

Jonathan Wendel, professor and chair, department of ecology, evolution and organismal biology, is a BCB faculty member. Dr. Wendel is a leader who was selected to be chair during a challenging time of Biological Sciences reorganization at ISU. Since that time, the ecology, evolution and organismal biology department has “evolved” into a department with an enviable reputation for excellence in research and teaching as well as collegiality. Dr. Wendel’s positive energy, enthusiasm, and a touch of humor work well to create a department that is welcoming and a good place to work. He has made campus-wide impacts as a leader in the development of the Biological Sciences programs, ADVANCE efforts, and as a mentor for other chairs.

Sad News for the BCB Program

Bob Farnham joined the Bioinformatics and Computational Biology (BCB) program in Fall 2006 to pursue his PhD. We are sad to say that he lost his battle with brain cancer on Saturday, August 22, 2009.

He had been fighting a reoccurrence of the cancer, which had initially appeared in November, 2001. In 2003, it was successfully treated into remission.  Unfortunately, the cancer returned in June 2007 and the biopsy at that time, as Bob described in an email to family and friends, revealed a grade 4 glioblastoma multiforme (GBM). His previous tumor was a grade 3 anaplastic astrocytoma. Until December, Bob had been undergoing chemotherapy treatments for this reoccurrence.

When it became clear Bob was failing, his major professor, Srinivas Aluru, and chair of BCB at the time, Chris Tuggle, were able to have a Masters degree awarded to Bob.  Srinivas and Suresh Kothari presented his diploma to him in Lamoni in April. Below are Suresh, Srinivas, Bob and Lynda.

Bob had a passion for family and friends and education. His dedication to interdisciplinary research and teaching at Iowa State immediately became apparent as he joined the interdisciplinary consultation organization, the BCB Lab. As part of the BCB Lab, Bob organized and led the creation of a computer cluster for use in bioinformatics research and teaching that is accessible to all students at Iowa State.

As a faculty member at Graceland University, Bob further established a connection between the Computer Science Department at Graceland and the BCB program at Iowa State in the spring of 2009. As part of this connection, a class of eight students from Graceland was able to utilize the Bioinformatics cluster at Iowa State to learn about algorithms and hardware architectures in parallel computing.

Bob has been a great mentor and colleague to all graduate students in the BCB program, especially his fellows in the Fall 2006 incoming class. His passion for interdisciplinary teaching and research and his enthusiasm for academic discussions has been an inspiration for pushing the limits of our knowledge and to always seek out opportunities to educate and cooperate with others in different disciplines.

Bob had wide ranging interests.  He was a ham radio operator, a strong-minded libertarian willing to discuss the Federal Reserve system at length, and took flying lessons in early 2000.  He had a wonderful speaking and singing voice, and students remember him fondly for making melodious announcements at the monthly BCB Thursday Night Suppers.  We will miss his warmth and enthusiasm and presence.

At the time of the reoccurrence of his cancer in June, 2007, Bob wrote to family and friends in an email:

"I want you to know how much we value your friendship and support.  We receive much strength from the knowledge that there are so many persons who care about us.  Nearly every day, we hear that we have been added to another prayer list.  We receive notes and calls from others who have us in their thoughts and prayers as well.  Just knowing there are so many caring people is tremendously helpful.  If I have learned anything through this, it is the importance of our relationships with other persons; in our families, in our circle of close friends, and in the local and more distant communities in which we interact with each other.  For when everything else falls apart, it is these relationships that will sustain us.  As the hymn text proclaims, Bear each others burdens, bear each others suffering, and love as the Savior has shown.

I also receive strength from Isaiah 41:30:  They that wait upon the Lord shall renew their strength; they shall mount up with wings as eagles; they shall run, and not be weary; they shall walk and not faint.  If I have had a blessing, it is truly remarkable that, over the past [nearly] six years since my original cancer diagnosis, I have been able to work full-time.  I have enjoyed a full life ... I have successfully completed my first year as a student at Iowa State University in the Bioinformatics and Computational Biology PhD program.  I have continued to participate in the lives of our children as they develop in their own lives.  I have experienced the joy of our two granddaughters, Briana and Kiera, who just turned four years old on June 18.  Although I had to give up my flying lessons in 2001, I feel that I can still soar with eagles.  I can run to catch the CyRide bus in Ames, and - except for my knees hurting - not be weary.  I can walk the mile or so from my apartment to most buildings on the ISU campus, and not faint.

Finally, I can empathize with Frodo of J.R.R. Tolkiens Fellowship of the Ring:  I wish none of this had happened.  So do I , said Gandalf, and so do all who live to see such times.  But that is not for them to decide.  All we have to decide is what to do with the time that is given us.  Lynda and I, our children Adam (with his fiance Sami), Corinne (with her husband Brian) Erin, and our extended families, all very much appreciate your caring support as we celebrate the joy of living for the time that is given us."

In Love,

Bob and Lynda Farnham

Student Activities/Achievements

Zaffarano Research Prize Awarded to Jeff Sander

Jeffry Sander, a BCB graduate student received Iowa State's prestigious Zaffarano Research Prize as a result of research done in Dr. Drena Dobbs' lab. He received his Ph.D. in December. He gave his final oral presentation entitlted "Characterization and design of C2H2 zinc finger proteins as custom DNA binding domains" in October. Here is an abstract of that talk:

As the storage medium for the source code of life, DNA is fundamentally linked to all cellular processes.  Nature employs hundreds of sequence-specific DNA binding proteins as transcription factors and repressors to regulate the flow of genetic expression and replication. By adapting these DNA-binding domains to target desired genome locations, they can be harnessed to treat diseases by regulating genes and repairing diseased gene sequences.

The C2H2 zinc finger motif is perhaps the most promising and versatile DNA binding framework.  Each C2H2 zinc finger domain (module) is capable of recognizing approximately three adjacent nucleotide bases in standard B form DNA.  Through directed mutagenesis, novel zinc finger modules (ZFMs) can be selected for most of the 64 possible DNA triplets.  By assembling multiple ZFMs with the appropriate linkers, zinc finger proteins (ZFPs) can be generated to specifically bind extended sequence motifs.

Several methods of varying complexity are currently available for ZFP engineering. ZFPs generated from the relatively simple modular design method often fail to function in vivo.  Those generated using the most reliable module subsets, those recognizing triplets with a 5' guanine (GNN), only function an estimated 50% of the time, while modularly assembled ZFPs comprised primarily of non-GNN modules rarely function in vivo.  These low success rates are extremely problematic for applications requiring multiple ZFPs targeting adjacent sequence motifs.  More complex approaches provide enhanced success rates as compared to modular design, with the drawback that they are also more labor intensive and require additional biological expertise.

In this work we engineered ZFPs, analyzed characteristics of functional engineered zinc finger proteins and their targets, formulated algorithms predictive of ZFP success for both modular assembly and OPEN (Oligomerized Pool Engineering) selection methods, and generated online software tools to aid others in the successful application of this technology.

He is pictured with Drena Dobbs, his major professor.

Jeff had his research results published in many journals detailing the computational design and experimental testing of zinc finger proteins. These can be used to target protein functional domains to virtually any DNA sequence of interest. Dobbs explained this has great implications for development of novel clinical therapies and they are being evaluated in several human clinical trials, including gene therapies to treat AIDS.

He is currently a postdoc in Molecular Pathology at the Massachusetts General Hospital and Harvard Medical School.

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Past Achievements of Note

Zaffarano Prize Winner - 2008 Zaffarano Prize for superior performance in publishable research by an ISU graduate student. Zaffarano Prize 2008 Winner, Scott Emrich, received his Ph.D. in August 2007 from the Bioinformatics and Computational Biology Interdepartmental Program and the Department of Electrical and Computer Engineering. His research is in bioinformatics, where he has done significant research in the area of genome assembly computations through gene sequencing and discovery, currently one of the most important frontiers in science and engineering.

Scott has had 14 outstanding, high impact publications spanning the diverse areas of computer science, bioinformatics, and plant sciences during the period he was a student at Iowa State. He was the primary author or the joint first author on the majority of publications, and three received special recognition when they were published. Scott was a key member of an Iowa State team involved in Maize genome sequencing. His major professor, Dr. Srinivas Aluru, says that Scott's work on maize genome assembly was the very first successful effort to assemble the sequences from pilot projects. Besides working on maize, Scott has applied similar techniques to sorghum. Dr. Patrick Schnable, Scott's co-major professor and Director of the Center of Plant Genomics, comments that the research team consisted of biologists and computational scientists with very different knowledge and perspectives and Scott served as a bridge between the two. His personality and scientific expertise played a significant role in forging the team's successful cross-disciplinary collaboration. Scott is now an assistant professor in the Department of Computer Science and Engineering at the University of Notre Dame.