Dr. Brian Poole, Department of Microbiology & 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 four peer-reviewed journal articles and one peer-reviewed book chapter. These are:

1. Daniel N. Clark, Jill Markham, Chad R. Sloan, Brian D. Poole. Cytokine Inhibition as a Strategy for Treating Systemic Lupus Erythematosus. Clinical Immunology 2012 Accepted for publication
2. Daniel N. Clark, Jared P. Lambert, Rodney E. Till, Kathryn E. Greenhalgh, Brandon Henrie, Tyson F. Hawkley, Lissenya B. Argueta, Marinya G. Roznik, 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 2012. Accepted pending revisions
3. Guthridge, Joel M.; Clark, Daniel N.; Templeton, Amanda; Dominguez, Nicolas; Lu, Rufei; Vidal, Gabriel; Kelly, Jennifer A; Kauffman, Kenneth; Harley, John B.; Gaffney, Patrick; James, Judith A.; Poole, Brian D. Effects of IRF5 lupus risk haplotype on pathways predicted to influence B cell functions. Journal of Biomedicine and Biotechnology. 2012; 2012: 594056
4. Clark Daniel N.; Poole, Brian D. Interferon and apoptosis in Systemic Lupus Erythematosus. In Systemic Lupus Erythematosus, Hani Almoallim, editor. Intech Publishing. 2012 pp 77-96.
5. Clark, Daniel N.; Poole, Brian D.; Hedman, Tyler J.; Hammond, Daniel V.; Catts, Daniel S.; Stewart, Amanda; Johnson, F. Brent. Characterization of herpes simplex virus clinical isolate Y3369 and its bearing on HSV typing. Virol J. 2011 Jun 9;8(1):290)

Three of the four journal articles have undergraduate student authors. We also have three manuscripts in progress using the data generated during the last funding period. Undergraduate students have presented their research in 11 presentations at two national and three statewide or regional scientific meetings.

Evaluation of the Mentoring Environment

The mentoring environment is strong. I am currently mentoring 13 undergraduates and 1 graduate student. I have mentored 40 undergraduate students 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 2011 MEG are listed. Only students receiving ORCA grants in the past year are listed.

Description of the Results/Findings of the Project

This project led directly to the writing of the manuscript “Molecular effects of the rs2004640 autoimmune risk allele on mRNA translational efficiency and exon choice in interferon regulatory factor 5.”which is now accepted for publication by the Journal of Interferon and Cytokine Research, pending some minor revisions. We found that a risk allele for Systemic Lupus Erythematosus in the IRF5 gene creates a transcript with a hairpin structure that suppresses translation. We also found that the risk allele allows for dramatically increased transcription of the IRF5 gene, as well as altered first exon usage and RNA splicing. These results have important implications for the etiology and pathogenesis of lupus.

The funding from the MEG also allowed for the publication of five other journal articles with student co- authors. These works include the mapping of gene pathways that are involved in the response to Epstein- Barr Virus infection in cells with the Lupus risk or protective IRF alleles, the discovery of a mutation in a clinical isolate of Herpes Simplex Virus that has worldwide implications on virus typing. Students were also able to participate in writing two review articles about the role of interferon and other cytokines in Lupus, and a book chapter about interferons in lupus.

With our MEG funding over the past two years, we were able to study the effects on apoptosis and interleukin-10 secretion of the IRF5 risk allele, and these studies are being polished and written up for publication. Our research led in exciting directions for new projects, including the evaluation of the IRF5 exon 1B promoter, and the development of reagents that are currently being used to generate preliminary data for submission of a grant to the NIH.

Description of how the budget was spent

Stipend for Daniel Clark, Ph.D. student: $10,000
Supplies: $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.