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Fall/Winter 2012

INSIDE FRALIN

Welcome to Fralin I want to welcome you to our Fall 2012 edition of Inside Fralin, our quarterly newsletter that keeps you updated on all the activities that are going on in the Fralin Life Science Institute. This edition is the first that we have printed, and not just sent out electronically; so, if you have a function and would like to take some copies to give out, please come see us and we’ll get you some.

The Fralin Life Science Institute is one of three investment institutes on campus. (The other two are ICTAS and ISCE). We are charged with furthering life science research at Virginia Tech and our mission statement says, in part, that “The Fralin Institute will strategically invest in targeted research areas within the life sciences. Such investments will include recruitment and set-up support for new faculty, retention and recognition of established faculty, seed funds for new research projects, equipment purchase, graduate student recruitment and support, undergraduate research support, and support of outreach activities.” I am proud to say that we met our mission in FY12 and we are working hard to meet it in FY13.

I thought that since the fiscal year has recently ended, I would give you an overview of what we spent our Educational and General (E&G) allocation on last year (FY12). The figure below shows the overall breakdown of these expenditures.

Total: approx. $1.9 million

A more detailed description of spending is on our website at http://www.fralin.vt.edu/about. As always, the Fralin staff are here to support you and aim to make it easier for you to do your job. We can help you with proposal development and submission, setting up websites and communicating your successes, and helping you with facility renovations and construction. Please let us know how we can help.

Associate Director, Fralin Life Science Institute

Research news..........................................................................2 Student Spotlight.......................................................................4 Outreach news..........................................................................6 Recent and upcoming events....................................................7


Research

Mosquito genetics may offer clues to malaria control Closely related African mosquito species originated the ability to transmit human malaria multiple times during their recent evolution, according to a study published Oct. 4, 2012, in PLoS Pathogens by Igor Sharakhov, an associate professor of entomology in the College of Agriculture and Life Sciences, and Maryam Kamali, a Ph.D. student in the department of entomology. The discovery could have implications for malaria control by enabling researchers to detect and target specific genetic changes associated with the capacity to transmit a parasite. Malaria causes as many as 907,000 deaths each year, mostly among children in sub-Saharan Africa. Anopheles mosquitoes, which bite mainly between dusk and dawn, transmit human malaria by spreading Plasmodium parasites that multiply in the human liver and infect red blood cells. But of the more than 400 species of mosquito belonging to the Anopheles genus, only about 20 are effective vectors of human malaria, according to the World Health Organization. The most dangerous of these is the Anopheles gambiae mosquito species, one of seven in the Anopheles gambiae complex, which was thought to have recently evolved the ability to transmit malaria. However, Virginia Tech scientists’ discoveries suggest that this species is actually genetically linked to an older, ancestral lineage. Scientists used chromosomal analysis to compare gene arrangements for mosquitoes both inside and outside the Anopheles gambiae family to trace the evolutionary connections. “The outside species served as a reference group for understanding the evolutionary relationship among Anopheles

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Igor Sharakhov and Maryam Kamali gambiae mosquitoes,” Kamali said. “Our goal was to determine how different species arose in the Anopheles gambiae complex, as they all look identical, but have different behaviors and capacities to transmit human malaria.” When resolving the Anopheles gambiae evolutionary history, the scientists identified breaks in DNA that lead to new chromosomal arrangements, and used these rearrangements to demonstrate the repeated evolution of the ability to transmit a parasite, in a back-and-forth fashion. “This curious stop-and-go flexibility could help us to better understand the nature of the mosquito’s capacity to transmit malaria, and calls into question what is driving the genetic flexibility,” Sharakhov said. The discovery is innovative in the field of genetics research. “The surprising aspect of the paper is the proposal of an ancestral and relatively ancient 2La polymorphism

which arose in a hypothetical ancestor and has been maintained in Anopheles gambiae ever since,” said Nora Besansky, the Rev. John Cardinal O’Hara C.S.C. professor of biological sciences at the University of Notre Dame, who was not involved in this study. “If confirmed, this would certainly lend novel insight into the evolutionary dynamics of chromosomal inversions in general, not only in mosquitoes.” Ai Xia, a former Ph.D. student of Sharakhov, and Zhijian Tu, professor of biochemistry in the College of Agriculture and Life Sciences, are co-authors on the paper. Kamali is the recipient of numerous awards and scholarships, including the Department of Entomology’s Scholarship for Outstanding Achievement in Systematic Entomology, the College of Agriculture and Life Sciences’ Cyrus McCormick Scholarship, and the 2008-2009 Fralin Life Science Institute Graduate Assistantship.


Drug screening laboratory available to life scientists A new laboratory in Fralin Hall, administered by the Virginia Tech Center for Drug Discovery, provides more than 35,000 chemical compounds for screening by Virginia Tech researchers. The three libraries of compounds were purchased from Analyticon, MicroSource, and Chembridge, and include natural products and synthetic drug-like compounds. The laboratory is equipped with robotic systems for assay preparation in microtiter plates and has the capacity to run biological assays based on fluorescence change, absorbance, and luminescence. The overall goal of the drug screening laboratory, according to the drug discovery center's director and University Distinguished Professor David Kingston, is to further the discovery of bioactive compounds. The plan is to steadily increase the number of compounds in the repository and the number of bioassays available. "Researchers can take two different approaches when using the laboratory,"

Pablo Sobrado, Nancy Vogelaar, and David Kingston said Kingston. "If they have a set of compounds they have made, they can have it tested in one of the assays available in the laboratory. Alternately, if they have developed a new assay, they can work with the screening laboratory to install their assay and test it against the compounds in the repository. This will probably lead to the discovery of bioactive compounds which can serve as lead compounds for

drug discovery." In order to use the screening laboratory’s services, researchers should contact the laboratory director Pablo Sobrado, associate professor of biochemistry and a principal participant of the Virginia Tech Center for Drug Discovery, or the facility manager Nancy Vogelaar.

Noted Publications “Carbon dioxide reduction to methane and coupling with acetylene to form propylene catalyzed by remodeled nitrogenase,” Zhi-Yong Yang, Vivian R. Moure, Dennis R. Dean, and Lance C. Seefeldt, Proceedings of the National Academy of Sciences, 2012. “Structure, Sulfatide Binding Properties, and Inhibition of Platelet Aggregation by a Disabled-2 Protein-derived Peptide.” Daniel Capelluto, Carla Finkielstein, Pavlos Vlachos, Rafael Davalos, Alireza Salmanzadeh, Xiangping Fu, John Charonko, Shyan Xiao. Journal of Biological Chemistry, 2012. “Effects of Incentives and Genetics on Food Choices and Weight Phenotypes in the Neuroendocrine Gene Tubby Mutant Mice.” George C. Davis, Johanna Jacob and Deborah J. Good. The Open Neuroendocrinology Journal, 2012. “Comparative Genomics of Early-Diverging Brucella Strains Reveals a Novel Lipopolysaccharide Biosynthesis Pathway.” Alice R. Wattam, Thomas J. Inzana, Kelly P. Williams, Shrinivasrao P. Mane, Maulik Shukla, Nalvo F. Almeida, Allan W. Dickerman, Steven Mason, Ignacio Moriyon, David O’Callaghan, Adrian M. Whatmore, Bruno W. Sobral, Rebekah V. Tiller, Alex R. Hoffmaster, Michael A. Frace, Cristina De Castro, Antonio Molinaro, Stephen M. Boyle, Barun K. De, and Joao C. Setubal. mBio, 2012.

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Education Rushing evolution

Millions of dollars of crop loss in the United States and billions of dollars worldwide can be attributed to Phytophthora sojae, a deadly plant pathogen attacking soybeans. Twin brothers and Ph.D. students Kevin and Mike Fedkenheuer are working in John McDowell’s lab with oomycete pathogens Phytophthora sojea and Hyaloperonospora arabidopsis to examine their molecular genetics and how they alter the immunological responses of soybean cultivars, Arabidopsis thaliana and other bean species. Oomycete pathogens contain effector proteins that suppress the plants immunological response and ability to fight off the pathogen. The pathogen infects the plant and secretes its proteins. However, in certain instances the plant identifies these effector proteins and is then able to defend itself from the pathogen. The Fedkenheuers are trying to determine which novel resistance genes make the plant able to identify effector proteins and determine the structural domains of these proteins recognized by the host. Ultimately, they would like to use this information to engineer resistance genes into the plants’ seeds.

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STUDENT SPOTLIGHT For two years, Kevin Fedkenheuer has worked with McDowell, an associate professor of plant pathology, physiology, and weed science in the College of Agriculture and Life Sciences and an affiliated faculty member with the Fralin Life Science Institute. Through a process called effector directed breeding, they work towards engineering a transgenic seed of elite soybean cultivar that is resistant to the P. sojea pathogen. Effector directed breeding involves growing hundreds of different soybean cultivars, infecting them with the pathogen, identifying which plants survive and then determining what resistance genes make it possible to identify and then fight off the pathogen. Once those novel resistance genes are found they will speed the process of evolution by breeding these genes into the elite soybean cultivar species used by the majority of farmers today. Concurrently, Kevin is also conducting transcript profiling of A. thaliana plants and the pathogen, H. arabidopsis. This

process involves “looking at how all the genes in the plant respond to the pathogen, which will determine its disease susceptibility,” said Kevin Fedkenheuer. On this project he is collaborating with researcher Brad Day, assistant professor of plant pathology at Michigan State University and Ruth Grene, professor of plant pathology, physiology, and weed science at Virginia Tech. “Kevin is a very bright and creative student. In only a few months, he set up a system for screening for new pathogen resistance genes, in soybean,” McDowell said. “I recently learned that a large group in China had been trying to set up a similar system for two years without success. Now we are going to collaborate with this group and they are going to use Kevin’s system. Kevin is also bringing new technologies into my lab as part of his second project on transcript profiling.” Mike Fedkenheuer is in his first year in McDowell’s lab and working on two projects. Much like Kevin’s first project,


Mike conducts effector directed breeding in beans and other legumes. He also hopes to engineer seeds that are resistant to the Phytophthora pathogens. “The benefit is that these seeds are not considered genetically modified,” he said. “The genes are already there, we just need to find them and breed them in; we are essentially rushing evolution,” said Kevin. In Mike Fedkenheuer’s second project he moves away from working with the plant and focuses specifically on the pathogens the conserved effector proteins in P. sojea and H. arabidopsis. Using a process called homology modeling, he seeks to identify the smallest structural domain within the protein that the plant recognizes to trigger an immunological response. A structural domain is a sequence of amino acids

within a protein that can function and fold independently without the rest of the protein. ”Finding the domain that is recognized by plants can reap several benefits, such as identifying effectors in other pathogen species or for intelligently designing proteins for plant immunity,” Mike Fedkenheuer said. “Mike is leveraging his previous training in structural biology and biochemistry to bring a new perspective and skill set to an ongoing project,” McDowell said. While working on his master’s degree, Mike Fedkenheuer worked in Pablo Sobrado’s lab for the Virginia Tech Drug Discovery Center, where he excelled at x-ray crystallography. This skill gives him an advantage in identifying structural domains in McDowell’s lab. His xray crystallography background includes

working at Virginia Tech’s Crystallography Laboratory and also at Brookhaven National Labs, NY, in their synchrotron facilities. “Mike had ‘the magic touch’ for crystallizing proteins,” Sobrado said. While working in Sobrado’s lab, Mike Fedkenheuer also co-authored two papers: Structural Insight into the Mechanism of Oxygen Activation and Substrate Selectivity of Flavin-Dependent N-Hydroxylating Monooxygenases and Dual role of NADP(H) in the reaction of a flavin dependent N-hydroxylating monooxygenase. A third is expected to be published soon. McDowell considers both Fedkenheuers assets to his lab. “As twins, it’s clear that Kevin and Mike share a rather unique intellectual synergy, and I’m looking forward to mentoring them in the upcoming years. “

Student Notes . Hassan Mahsoub, a graduate student working with Dr. Frank William Pierson and Dr. Roger Avery, won Second Place Poster Presentation Award at the Virginia Tech Graduate Research Symposium, for his poster entitled “Improved methodology for titration of hemorrhagic enteritis (HE) vaccines using real-time quantitative polymerase chain reaction (qPCR).” . Mary Etna Haac, a Ph.D. student in Dr. Zach Adelman’s lab, received the Virginia Tech’s Gladys and Clarence Hill Travel Scholarship to present her research findings at the Third Panamerican Dengue Research meeting in Cartegena, Columbia. . Ngoc Pham, a master’s student in Dr. Troy Anderson’s lab, and Astha Verma, a Ph.D. student in Dr. Paul Carlier’s lab, received third and first place poster awards, respectively, from the Division of Agrochemicals at a recent American Chemical Society meeting. . Plant Pathology, Physiology and Weed Science Symposium poster winners were: Michael Cox for “Annual Bluegrass Control in Kentucky Bluegrass with Amicarbazone,” Shi Yu for “Myristoylation of LOSS OF GDU2 a E3 Ubiquitin Ligase is Important for Its Membrame Localization and the Interaction with GLUTAMINE DUMPER1,” and Gunjune Kim for “Parasitic Plants Exchange Wide Range of mRNAs with Hosts.”

Ngoc Pham and Astha Verma

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Outreach

Bioengineering kit available through Biotech-in-a-Box This year, Fralin Life Science Institute’s Biotech-in-a-Box program, with funding from the Howard Hughes Medical Institute, is introducing a new bioengineering kit that combines concepts from both biology and engineering. The kit, which contains materials and instructions for students to run six experiments investigating the development and manufacture of wound dressings, is available to high schools and community colleges across Virginia. The experiments, which compare materials as diverse as gauze pads and hydrocolloid dressings, examine material characteristics such as elasticity and permeability. Students must consider factors such as the type of wound being treated, the dressing’s biocompatibility, the product cost, ease of sterilization, and the environmental impact of production. The kit was specifically designed to educate students on how to determine the physical parameters of materials, and to evaluate their results in terms of the design and purpose of the dressings. “It is not common that an engineer examines just one part of a product, and that is something this new kit showcases. It was created to familiarize students with the idea of examining products from multiple perspectives,” said Kristi DeCourcy, research associate and laboratory manager at the Fralin Life Science

Kristi DeCourcy, founder of the Biotech-in-a-Box program Institute and founder of the Biotech-ina-Box program. DeCourcy develops and distributes the Biotech-in-a-Box kits, which have successfully reached over 100,000 students across almost every county in Virginia since the program’s inception in 1994.

across Virginia and offer students the opportunity to use science equipment that is not readily available in the typical classroom.

The Bioengineering kit is one of six available kits; others explore DNA, protein structure, immunology, and the behavior of organisms. The kits are Biotech-in-a-Box is exactly what it loaned to teachers for two weeks and are sounds like -- boxes full of learning then sent back to Fralin to be prepared tools, equipped with experiments ready to go to another classroom for use. All for classroom use. The kits are loaned to costs for the kits, including shipping, are high schools and community colleges paid by Fralin.

Upcoming News Pulaski County High School students take learning to the next level when they use the protein electrophoresis kit on loan from Fralin’s popular Biotech-in-a-Box outreach program. Look for the story in the winter issue of Virginia Tech’s Research Magazine!

www.research.vt.edu/resmag/

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EVENTS Virginia Tech Life Science Seminars (VTLSS) (all held at 12:20 p.m. in the Virginia Bioinformatic Institute’s Conference Center)

Approximately 200 Fralin, VBI and VTCRI faculty members attended a faculty mixer held Oct. 9 at the Inn at Virginia Tech. Presentations included the 2013 fiscal year budget, and a proposed health sciences graduate program.

Nov. 9: “New paradigms for plant disease epidemiology and for the role of plant-associated micro-organisms in Earth system processes”, Dr. Cindy Morris, director of the Plant Pathology Research Unit at the French National Institute for Agricultural Research Nov. 16: “Building rapidly perfused vascular networks using human endothelial and mesenchymal progenitor cells,” Dr. Joyce Bischoff, research associate and professor at Boston Children’s Hospital Nov. 30: “High Throughout Cell-Based Studies and Protein Microarrays for Biomarker and Target Discovery,” Dr. Joshua LaBaer, director of Personalized Diagnostics at The Biodesign Institute at Arizona State University

Brochures, mugs, and candy were given out at the Fralin booth at Hokie Bugest 2012, held Oct. 20 at the Inn at Virginia Tech, and put on by the VT entomology department. Have an upcoming event? Let us help you promote it within the life sciences community! Contact Lindsay Key at ltkey@vt.edu or Cecilia Elpi at ceciliae@vt.edu!

Dec. 7: “Type III Effectors and the Plant Immune Response,” Dr. Darrell Desveaux, associate professor of cell and systems biology and the University of Toronto

About VTLSS The Virginia Tech Life Science Seminar series is an interdepartmental seminar series funded by Fralin, the College of Agriculture and Life Sciences, and the Virginia Bioinformatics Institute, in an effort to promote education and collaboration with peers outside the university. Look for announcement of the Spring 2013 Series soon on the Fralin website! www.fralin.vt.edu/vtlss

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About Fralin The Fralin Life Science Institute is an investment institute committed to supporting research, education, and outreach in Virginia Tech’s life sciences community. Residents of the institute’s four flagship buildings are automatically considered affiliated faculty members and all other life science researchers on campus are invited to become affiliated faculty members. Affiliated faculty members are given resources necessary to explore new, innovative science that benefits people in the New River Valley, the Commonwealth of Virginia, and the world. Through seminars, conferences and research group support, the institute serves as a meeting point for progressive ideas involving multidisciplinary research. It is closely aligned with Virginia Tech’s other six research institutes, which include the Virginia Tech Carilion Research Institute, Virginia Tech Transportation Institute, the Institute for Critical Technology and Applied Sciences, the Virginia Bioinformatics Institute, the Institute for Society, Culture and Environment, and the Institute for Creativity, Arts and Technology. Research initiatives within the life sciences receiving the highest priority for support include vectorborne disease, infectious disease, plant sciences, ecology and organismal biology, obesity, and cancer biology. The Fralin Life Science Institute is also actively engaged in cooperative partnerships with colleges, departments, and other institutes that also support the life science community.

We are now on social media! www.fralin.vt.edu

Horace Fralin, university benefactor

Fralin Life Science Institute Fralin Biotechnology Center West Campus Drive, Room 101 Virginia Tech 0346 Blacksburg, VA 24061 540-231-6933 (v) 540-231-7126 (f)

Fralin News  

Fralin Newsletter Fall/Winter 2012