PI: Brian Poole
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 were used to publish two peer-reviewed journal articles:
- Cornaby, Caleb; Jafek, Jillian L.; Birrell, Cameron; Mayhew, Vera; Syndergaard, Lauren; Mella, Jeff; Cheney, Wesley; Poole, Brian D. EBI2 expression in B lymphocytes is controlled by the Epstein-Barr virus transcription factor, BRRF1 (Na), during viral infection. Journal of General Virology, 2016. Accepted pending revisions; resubmitted Oct 2016.
- Cornaby, Caleb; Tanner, Anne; Stutz, Eric; Poole, Brian D.; Berges, Bradford K. Piracy on the molecular level: human herpesviruses that manipulate cellular chemotaxis. Journal of General Virology, December, 2015. Doi 10.1099/jgv.0.000370
All three of the journal articles have BYU student authors, indicated by bold in the above citations. We also had an additional manuscripts in progress using the data generated during the funding period. This was submitted and accepted during 2015.
- Cornaby, Caleb; Gibbons, Lauren; Mayhew, Vera; Sloan, Chad S.; Welling, Andrew; Poole, Brian D. B cell epitope spreading: Mechanisms and contribution to autoimmune diseases. Immunology Letters. January 2015: 163(1) 56-68. doi:10.1016/j.imlet.2014.11.001
Five presentations with nine student authors were presented at two national and one regional scientific meeting during the funding period.
Evaluation of the Mentoring Environment:
The mentoring environment is strong. I am currently mentoring 17 undergraduates and 1 graduate student. I have mentored over 80 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 2015-2016 MEG are listed.
Description of the Results/Findings of the Project:
Lupus is a complex disease, with genetic, environmental, and hormonal influences. Interferon Regulatory Factor 5 is one of the genes with polymorphisms most strongly associated with risk for lupus. Interestingly, those polymorphisms do not affect the protein-coding region of the IRF5 gene. We investigated how the risk haplotype affects transcription and splicing of the IRF5 gene. Our previous research demonstrated that the major contribution of the risk haplotype was an increase in expression of the IRF5 gene.
To further pursue this finding, we developed a vector that overexpresses the IRF5 gene. We characterized the vector and used it to transfect B cells. We also developed a vector that expresses IRF5, but without the DNA-binding domain, both to use as a control and to investigate the importance of the different domains of the protein.
We used this vector to transfect naïve B cells that we isolated from volunteers. We then stimulated the B cells and examined them for activation-induced cell death, testing the hypothesis that increased IRF5 expression would lead to decreased cell death. This was the case, with our IRF5-transfected B cells exhibiting significantly less apoptosis than the control-transfected cells. This strongly suggests that overproduction of IRF5 in cells with a lupus genetic risk background contributes to loss of tolerance and the survival of autoreactive B cells.
We are continuing to study the effects of IRF5 overexpression by looking at calcium mobilization and other signs of cell responsiveness in cells transfected with the IRF5 vector.
Description of how the budget was spent:
Stipend for Daniel Clark, Ph.D. student: $7,000
Due to the generosity of the college and MMBIO department, we were able to pay for undergraduate wages and travel costswithout using the MEG funds.