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INVESTIGATOR: Wilusz, J.; Quackenbush, S.

PERFORMING INSTITUTION:
COLORADO STATE UNIVERSITY
FORT COLLINS, COLORADO 80523

ANIMAL BIOSECURITY PATHOLOGY TRAINING GRANT

NON-TECHNICAL SUMMARY: This program is designed to create 2 well-trained PhD-level animal pathologists with in-depth biosecurity awareness to help address the growing national need in this area. We will use a variety of coursework and experiential learning activities to accomplish this goal.

OBJECTIVES: This project focuses on the Targeted Expertise Shortage Area of Sciences (TESA) for Agricultural Biosecurity, specifically in the area of animal pathology. It will address discipline code X (Agricultural Biosecurity). The goal of the proposal is to train two national needs fellows at the doctoral level specifically in the area of animal pathology with a strong emphasis in biosecurity. This will be accomplished through a three year integrated training experience involving investigative pathology, diagnostics and biosecurity/biosafety that takes full advantage of the extensive resources in these three areas available at Colorado State University. Four innovative aspects of our animal pathology biosecurity training program include (1) A close knit connection between this training program and the ~35million dollar NIH funded Rocky Mountain Center for Biodefense which provides a rare and outstanding opportunity for students to receive training in both animal pathology and biosecurity. (2) Industry connections between our training program and regional and national agricultural and biotechnology industries is available through the CSU Infectious Disease Supercluster (also called MicroRX). (3) Efforts are currently underway to create a parallel certificate program in biosafety/biosecurity to help address the national need in this area. (4) The plethora of research opportunities in our department supported by ~$33 million in extramural funding will provide a goldmine of exposure of trainees to many areas of pathology and pathogenesis. A detailed set of eleven independent assessment rubrics are in place and will be applied annually to ensure trainee progress. Finally, a strong defined administrative structure will promote the smooth operation and effective delivery of the Program. This program will have national impact in that it will develop 2 well-trained PhD-level animal pathologists with in-depth biosecurity awareness to help address the TESA.

APPROACH: The goals of this program will be accomplished through a three year integrated training experience involving investigative pathology, diagnostics and biosecurity/biosafety that takes full advantage of the extensive resources in these three areas available at Colorado State University. The new training program will involve more than 20 core faculty members who have an excellent record of mentorship and collaboration. In addition to extensive research opportunities, 25 graduate level pathology, infectious disease and biosafety courses, along with a comprehensive course in the responsible conduct of research, are available for trainees to provide a strong theoretical foundation for the Program. Frequent seminars, journal clubs, grantsmanship/laboratory management workshops and an annual retreat will ensure a high level of communication in the Program as well as a well-rounded training experience. A detailed set of 11 assessment rubrics are in place and will be applied annually to ensure trainee progress. These rubrics include the ability to digest and apply course material, oral and written communication skills, ability to interpret data and pose hypotheses, knowledge of 21st century lab skills, ability to work independently, the responsible conduct of research and post-graduation follow-ups to monitor to overall impact of the program.

PROGRESS: 2010/01 TO 2014/12
Target Audience: Two graduate students seeking to obtain their PhD degree (Marta Lishnevsky and Stephanie Moon) were the focus of this award. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? As indicated above, this project has provided the coursework foundation and laboratory experiences for the development of two PhD-level scientists. This training also includeda formal coursein 'grant writing' along with other professional development activities to build the students communication skills that will be invaluabel for future success. How have the results been disseminated to communities of interest? Throughout the lifespan of this Award, all results have been disseminated through publications in major journals as well as meeting presentations - including regional,national and international conferences in the field What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

IMPACT: 2010/01 TO 2014/12
What was accomplished under these goals? This training program will have reached its stated goal in the Spring of 2014 by successfully training two PhD graduates in the area of animal pathology. Marta Lishnevsky received her PhD in 2013 and is doing a postdoctoral fellowship at Baylor University.As listed above, Marta published one additional paper (first author journal article) with her mentor Dr. Alan Schenkel. Stephanie Moon continued her highly productive graduate work by publishing two papers in a collaborative project. One of these papers wasin the highly respected journal 'Science'.The NIFA training proposal was not acknowledgedon these papers as the work wasperformed after her support from the award had ended. Stephanie defended her PhD dissertaion in the Summer of 2014 and is currently a postdoctoral fellow working at the University of Colorado in Boulder in the laboratory of Dr. Roy Parker.

PUBLICATIONS (not previously reported): 2010/01 TO 2014/12
1. Type: Journal Articles Status: Published Year Published: 2014 Citation: Chapman EG, Moon SL, Wilusz J, Kieft JS. (2014). RNA structures that resist degradation by Xrn1 produce a pathogenic Dengue virus RNA. Elife. Apr 1;3:e01892. doi: 10.7554/eLife.01892.
2. Type: Journal Articles Status: Published Year Published: 2014 Citation: Chapman, E.G., Costantino, D.A. Rabe, J.L. Moon, S.L. Wilusz, J., Nix, J.C. and Kieft, J.S. (2014). The structural basis of pathogenic subgenomic flavivirus RNA (sfRNA) production. Science, 344: 307-310.
3. Type: Journal Articles Status: Published Year Published: 2014 Citation: Lishnevsky M, Young LC, Woods SJ, Groshong SD, Basaraba RJ, Gilchrist JM, Higgins DM, Gonzalez-Juarrero M, Bass TA, Muller WA, Schenkel AR. Microhemorrhage is an early event in the pulmonary fibrotic disease of PECAM-1 deficient FVB/n mice. Exp Mol Pathol. 2014 Aug;97(1):128-36.

PROGRESS: 2013/01/01 TO 2013/12/31
Target Audience: Two graduate students seeking to obtain their PhD degree ( Marta Lishnevsky and Stephanie Moon) are the focus of this award. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? As indicated above, this project has provided the coursework foundation and laboratory experiences for the development of two PhD-level scientists. How have the results been disseminated to communities of interest? Results have been disseminated through publications in major journals as well as meeting presentations - including regional, national and international conferences in the field What do you plan to do during the next reporting period to accomplish the goals? One student finished her PhD in 2013 and the other trainee (Ms. Moon) is nearly done writing her dissertation and will defend in the Spring 2014. Therefore the next reporting period will simply involve the final PhD defense of the program and a small celebration for the successful completion of all of the aims of this project.

IMPACT: 2013/01/01 TO 2013/12/31
What was accomplished under these goals? In summary, the training program will have reached its stated goal in the Spring of 2014 by successfully training two PhD students in the area of animal pathology. I am pleased to report that Marta Lishnevsky received her PhD in 2013 and has recently started a postdoctoral fellowship at Baylor University. Marta published one editorial with her mentor Dr. Alan Schenkel in the Journal of Immunology & Clinical Research (Lishnevsky M, Schenkel AR (2013) Contusions, Blood Leakage, and the Immune Response. J Immunol Clin Res 1: 1010.) Stephanie Moon had a very productive year in the program. She was co-first author on a Cell Reports manuscript that received two recommendations from the Faculty of 1000. She also published a review article in Plos Pathogens in December that was an invited ‘PLoS Pearls’ paper. Additional papers are in the pipeline. She is currently writing her dissertation and plans to defend her dissertation in March and graduate in May. She has lined up postdoctoral training in the discipline at the University of Colorado, Boulder. Recently, Stephanie received an ‘Honors’ award for her poster presentation at our local graduate student recruitment day in February 2014.

PUBLICATIONS: 2013/01/01 TO 2013/12/31
1. Type: Journal Articles Status: Published Year Published: 2013 Citation: Barnhart MD, Moon SL, Emch AW, Wilusz CJ, Wilusz J. (2013) Changes in Cellular mRNA Stability, Splicing, and Polyadenylation through HuR Protein Sequestration by a Cytoplasmic RNA Virus. Cell Reports 5: 909-917.
2. Type: Journal Articles Status: Published Year Published: 2013 Citation: Moon SL, Wilusz J. Cytoplasmic viruses: rage against the (cellular RNA decay) machine. PLoS Pathog. 2013 Dec;9(12):e1003762. doi: 10.1371/journal.ppat.1003762. Epub 2013 Dec 5.

PROGRESS: 2012/01/01 TO 2012/12/31
OUTPUTS: Since May, 2010, two excellent students have been participating in this training program - Ms. Marta Lishnevsky and Ms. Stephanie Moon. Thus our retention rate through 2102 continues to be 100%, a strong indicator that our program is effective. In 2012, Ms. Lishnevsky is finished with her formal coursework in the training program and continued her work in the laboratory of Dr. Alan Schenkel to study microhemmorrhaging and the pathology of pulmonary fibrotic disease using a mouse model. She presented one poster at a regional meeting. Notably, she gave an invited talk at an institution in Denver CO in 2013 and submitted a manuscript to Disease Models and Mechanisms for publication. She is tentatively planning her PhD defense seminar for May 2013, and thus will likely be the first graduate of our Training Program. Ms. Stephanie Moon is continuing to make outstanding progress towards her PhD degree in the laboratory of Dr. Jeffrey Wilusz focusing on molecular aspects of viral pathogenesis and cytopathology. In 2012, she presented 5 abstracts at local and national meetings. Notably, she received two awards for these presentations - a first place graduate student speaker award from the Rocky Mtn Virology Association and High Honors at the multi-program research symposium held at CSU in conjunction with new graduate student recruitment in Feb 2012. Stephanie also published three papers as first author that are listed below. In summary, both trainees performed very well this year and are well on their way to obtaining the PhD degree and fulfilling the grant's main output goal of producing two PhD-level trainees in this field. Overall our Training Program Steering Committee remains satisfied with the training regimen and the progress of these students As reported previously, the results of our program will be disseminated in a number of key ways. Publications in respected peer-reviewed journals will be generated by the trainees that will significantly contribute to our understanding of animal health and disease. Stephanie Moon, for example, published three such manuscripts in 2012 and is working on 3 more for 2013. Students will continue to regularly presenting their research findings at regional, national and international meetings (and with a little luck, continue to receive awards for their efforts which the Program Steering Committee is particularly proud of). Web-based notifications of progress/key accomplishments of trainees are regularly disseminated in the department/college via our monthly newsletter. PARTICIPANTS: PI/PD: Dr. Jeffrey Wilusz - served as Director of the Training Program and monitors student progress co-PI: Dr. Sandra Quackenbush - Associate Dept Head for Graduate Education serves as co-Director of the Program and assists the Director when needed. Trainees - Stephanie L. Moon and Marta Lishnevsky - these students are working towards their PhD degrees as part of the Training Program funded by this award. Primary Mentors of Trainees: Drs J. Wilusz and Alan Schenkel - serve as the primary research mentors for trainees Moon (Wilusz) and Lishnevsky (Schenkel). TARGET AUDIENCES: Not relevant to this project. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

IMPACT: 2012/01/01 TO 2012/12/31
We are well on our way (likely within this calendar year) to accomplishing the designated output goal of this grant - The generation of two well-trained PhD level scientists that will substantially contribute to US animal health over the course of their careers. Biosecurity is not only of major importance to the US agricultural community but also to US society as a whole. This training program will generate two well-trained PhD researchers in the pathological aspects of animal biosecurity. This increase in our workforce in this area is vital to effectively address microbial threats and preserve the integrity of our food supply. The training program that was established by this award is unique in our region and should serve as a model for future related training initiatives in the state/region.

PUBLICATIONS: 2012/01/01 TO 2012/12/31
1. Moon, S.L., J.R. Anderson, Y. Kumagai, C.J. Wilusz, S. Akira, A.A. Khromykh, J Wilusz. (2012). A noncoding RNA produced by arthropod-borne flaviviruses inhibits the cellular exoribonuclease XRN1 and alters host mRNA stability. RNA. 18(11):2029-40. doi: 10.1261/rna.034330.112.
2. Moon, S.L., M.D. Barnhart, J. Wilusz. (2012). Inhibition and avoidance of mRNA degradation by RNA viruses. Curr Opin Microbiol. 15(4):500-5. doi: 10.1016/j.mib.2012.04.009.
3. Moon, S.L., and J. Wilusz. (2012). In vitro transcription of modified RNAs. Methods Mol Biol. 941:171-80. doi: 10.1007/978-1-62703-113-4 13.

PROGRESS: 2011/01/01 TO 2011/12/31
OUTPUTS: In May, 2010 we appointed two excellent students to this training program - Ms. Marta Lishnevsky and Ms. Stephanie Moon who have continued in the program through 2011. Thus our retention rate is 100%, a sign in our opinion that the program is meeting its goal. This was a year that can best be described as one where our trainees put their nose to the grindstone and finished up their formal coursework and made substantial progress in the research side of their projects. Ms. Lishnevsky continues to work in the laboratory of Dr. Alan Schenkel. In 2011 she reached a major milestone in her training by passing her preliminary examination to become a candidate for the PhD degree in our program. She continues to perform well in classes as her GPA is now 3.87 out of 4.0. She made one international meeting presentation at the International Thoracic Society Conference that was well received. In summary, Ms. Lishnevsky's progress has been solid. Stephanie. Moon continues to pursue her research project in the laboratory of Dr. Jeffrey Wilusz and has achieved a number of important training milestones this grant year. First and foremost, she passed her preliminary examination for PhD candidacy on November 8, 2011. Stephanie has also received a number of awards for her research work at several regional meetings in her field. She received an Honors award for a poster presented at the highly competitive CSU Multi-Program Recruiting Day Symposium in February 2011. She also received two second place awards for her platform oral preserntation of her work at the Rocky Mountain Branch of the American Society for Microbiology meeting in April 2011 and at the Rocky Mountain Virology Association meeting in September 2011. Her graduate coursework GPA is a crisp 3.932/4.0. Interestingly, Stephanie also received an Honorable Mention at the annual CSU Science and Art Exhibition held in March 2011. Thus from the numerous perspectives, Ms. Moon is progressing very well. Overall our Training Program Steering Committee is very pleased with the training regimen and the progress of these students to date. The results of our program will be disseminated in various ways. Publications in respected peer-reviewed journals will be generated by the trainees that will significantly contribute to our understanding of animal health and disease. Stephanie Moon is currently preparing her research findings for a first author manuscript that will be submitted to a major journal in the infectious disease field. Students will continue to regularly presenting their research findings at regional, national and international meetings. Web-based notifications of progress/key accomplishments will be generated on a regular basis through our departmental newsletter. PARTICIPANTS: Two trainees participated in our program: Stephanie L. Moon Marta Lishnevsky Details of their participation and progress in the training program have been discussed above TARGET AUDIENCES: Not relevant to this project. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

IMPACT: 2011/01/01 TO 2011/12/31
We are well on our way to accomplishing the output goal of this grant: The generation of two well-trained PhD level scientists that will substantially contribute to US animal health over the course of their careers. Biosecurity is not only of major importance to the US agricultural community but also to US society as a whole. This training program will generate two well-trained PhD researchers in the pathological aspects of animal biosecurity. This increase in our workforce in this area is vital to effectively address microbial threats and preserve the integrity of our food supply. The training program that was established by this award is unique in our region and should serve as a model for future, related training initiatives in the state and region.

PUBLICATIONS: 2011/01/01 TO 2011/12/31
Moon, S. L. and J. Wilusz. (2011) In vitro transcription of modified RNAs. Volume TBD in Methods of Molecular Biology, Graeme Conn, ed. Humana Press, In Press.

PROGRESS: 2010/01/01 TO 2010/12/31
In May, 2010 we appointed two excellent students to this training program - Ms. Marta Lishnevsky and Ms. Stephanie Moon. The recruitment of these two students is a major milestone in our training program as our available slots are now filled. Ms. Lishnevsky is working in the laboratory of Dr. Alan Schenkel and Ms. Moon is doing her research in the laboratory of Dr. Jeffrey Wilusz. Both students have been progressing well and have achieved some notable training milestones as well in their first 7 months in the Training Program. Ms. Stephanie Moon won second place in the graduate student poster competition at our regional Rocky Mountain Virology Meeting in Pingree Park CO in September. An abstract on her involving mechanisms of cytopathology of viral infections is planned for the national ASV meeting in July 2011. She also performed well in all 11 didactic credits of her course work in the Fall 2010 semester. Stephanie finished her biosafety training and certification by the CSU Biosafety Office in Fall 2010. Additionally, she was a member of the Department's student seminar committee and joined a professional society in her field of interest. Thus from the perspective of her coursework, research productivity, presentation skills and the development of career networking opportunities, Stephanie is progressing very well. Ms. Marta Lishnevsky achieved a 4.0 GPA for her coursework in the Fall 2010 semester and was awarded an A+ for her research efforts by her advisor Dr. Schenkel. Marta received a travel award and presented a poster at the American Thoracic Society meeting in New Orleans this year on her work on pulmonary fibrosis. A manuscript on this work is in preparation. Marta completed CSU Biosafety Training this year and joined a professional society in her field of interest (ATS). Marta's preliminary examination for PhD candidacy is scheduled for February 2011. Thus Marta's training and professional development appear to be going smoothly as well. PRODUCTS: Two PhD level researchers will be trained and will join the work force involved in the animal biosecurity with an emphasis on pathology OUTCOMES: Two well-trained PhD level scientists will be generated that will substantially contribute to US animal health over the course of their careers. DISSEMINATION ACTIVITIES: Publications in respected peer-reviewed journals will be generated by the trainees that will significantly contribute to our understanding of animal health and disease. Students will continue to regularly presenting their research findings at regional, national and international meetings. Web-based notifications of progress/key accomplishments will be generated on a regular basis through a departmental newsletter. FUTURE INITIATIVES: The training program that was established by this award is unique in our region and should serve as a model for future, related training initiatives in the state and region.

IMPACT: 2010/01/01 TO 2010/12/31
Biosecurity is not only of major importance to the US agricultural community but also to US society as a whole. This training program will generate two well-trained PhD researchers in the pathological aspects of animal biosecurity. This increase in our workforce in this area is vital to effectively address microbial threats and preserve the integrity of our food supply.

PUBLICATIONS: 2010/01/01 TO 2010/12/31
No publications reported this period