Brian Poole, Microbiology and Molecular Biology
Evaluation of how well the academic objectives of the proposal were met:
The academic objectives of this proposal were met. Using the funding provided by the MEG, we generated data that was used to publish three peer-reviewed journal articles:
- Daniel N. Clark, Jared P. Lambert, Rodney E. Till, Lissenya B. Argueta, Marinya G. Roznik Kathryn E. Greenhalgh, Brandon Henrie, Tyson F. Hawkley, Jason M. Sloan, Trieste Bills, Loc Woodland, Eric P. Nelson, Meng-Hsuan Tsai, Brian D. Poole. Molecular effects of the rs2004640 autoimmune risk allele on mRNA translational efficiency and exon choice in interferon regulatory factor 5. Journal of Interferon and Cytokine Research. 2014 May;34(5):354-65. doi: 10.1089/jir.2012.0105.
- Daniel N. Clark, R. D. Read, Vera Mayhew, Stephen C. Petersen, Lissenya B. Argueta, Lance A. Stutz, Rodney E. Till, Sean M. Bergsten, Brandon S. Robinson, Douglas G. Baumann, J. C. Heap and Brian D. Poole. Four promoters of IRF5 respond distinctly to stimuli and are affected by autoimmune-risk polymorphisms. Front. Immunol. 2013. doi: 10.3389/fimmu.2013.00360
- Caleb Cornaby, Lauren Gibbons, Vera Mayhew, Chad S. Sloan, Andrew Welling, Brian D. Poole. B cell Epitope Spreading: Mechanisms and Contribution to Autoimmune Diseases. Accepted for publication pending review, Immunology Letters.
All three of the journal articles have undergraduate student authors. We also have two manuscripts in progress using the data generated during the last funding period. These will both be submitted by the end of 2014
- Lissenya Argueta, Rodney Till, Brian D. Poole. Epstein-Barr virus. In Viral Arthritis, Stanley J. Naides, Editor. Manuscript in preparation. Estimated submission date Nov 31, 2014.
- Caleb Cornaby, Jillian Markham, Cameron Birrell, Brian D. Poole. Mechanisms and timing of the activation of the EBI2 gene by Epstein-Barr Virus. Manuscript in preparation: Estimated submission date Dec 1 2014
Two undergraduate students presented their research at an international conference during the funding period.
Evaluation of the Mentoring Environment:
The mentoring environment is strong. I am currently mentoring 11 undergraduates and 1 graduate student. I have mentored 65 undergraduate students and three graduate students in my lab during my time at BYU. Many of these students have since moved on to graduate school, scientific employment, medical school, and dental school, among other pursuits.
My students are skilled at reading, analyzing, and using primary literature due to our journal club. They are evaluated by me and the other students at journal clubs, showing their proficiency. They are skilled at laboratory techniques and designing and analyzing experimental results due to their experience working in the lab and the system of responsibility for their own projects. Evidence for this is the strong number of papers that have been accepted for publication, and which all had sections written by the undergraduates. The research in these papers was performed by the undergraduates in large part. Their scientific writing has improved due to their writing of ORCA grants, which I require for each student, although not all are submitted.
List of students and academic deliverables.
Only students who were in the lab during the time of the 2013-2014 MEG, are listed.
|Rodney Till||2 Journal Articles, 1 Presentation, 1 ORCA Grant Funded|
|Jeffrey Mella||1 Presentation, 1 ORCA grant awarded|
|Jillian Markham||1 Journal Article, 1 ORCA grant awarded|
|Lissenyi Argueta||2 Journal Articles, 1 ORCA grant awarded|
|Michael Ahlborn||1 ORCA grant awarded|
|Vera Mayhew||2 Journal Articles, 1 ORCA grant awarded|
|Lauren Gibbons||1 Journal Article, 1 ORCA grant awarded|
|Marinya Rosnick||1 Journal Article, 1 ORCA grant awarded|
|Jared Lambert||1 Journal Article|
|Jason Sloan||1 Journal Article|
|Eric Nelson||1 Journal Article|
|Stephen Peterson||1 Journal Article|
|Lance Stutz||1 Journal Article|
|Chad Sloan||1 Journal Article|
|Andrew Welling||1 Journal Article|
|Caleb Cornaby (MS student)||2 Journal Articles|
|Daniel Clark (Ph.D. Student)||6 Journal Articles, 8 Presentations|
|Allison Youngberg||New in lab|
|Andrew Miner||New in lab|
|Cameron Birrell||New in lab|
|Eric Stutz||New in lab|
|Maite Antola||New in lab|
|Samantha Sorensen||New in lab|
|Steven Thrap||New in lab|
Description of the Results/Findings of the Project:
This project led directly to the writing of the manuscript “Mechanisms and timing of the activation of the EBI2 gene by Epstein-Barr Virus” which is slated for submission to Journal of Virology before the end of 2014. Our work with EBV also lead to an invitation to author a book chapter, “Epstein-Barr Virus” in the upcoming scholarly book Viral Arthritis. The drafts for this book chapter are due by Nov 30th, 2014. The funding from the MEG also allowed for the publication of three other journal articles with student co- authors. These works were finishing up our previous work on IRF5 in lupus, and a review article dealing with how pathogens, such as Epstein-Barr virus, contribute to the spreading of immunity and autoimmune disease.
We had several unexpected findings during this project. We found that EBI2 expression is transient after infection with EBV, and that long-term infected cells actually express this gene at very low levels. We investigated the viral genes responsible for EBI2 expression and found that BRRF1, a viral gene expressed during lytic infection and early EBV infection, has an excellent correlation with EBI2 expression. Furthermore, the use of a recombinant virus that does not express BRRF1 does not upregulate EBI2. General cell stimulation also does not increase the levels of EBI2.
Since EBI2 is important in terms of establishing the adaptive immune response and for B cell movement and localization, it is important to know how this gene is regulated by infection with Epstein-Barr virus. The experiments done using this grant demonstrate that EBI2 is upregulated early in infection and during latent infection. The virus likely uses this gene to force B cells to areas where other B cells cluster, making infection and viral spread more efficient.
Description of how the budget was spent:
Stipend for Daniel Clark, Ph.D. student: $10,000
Due to the generosity of the college and MMBIO department, we were able to pay for undergraduate wages and travel without using the MEG funds.