'Understanding the role of host lipid mediators during H1N1 infection' - MIMM 397 Undergraduate Research Project Application Form.

INSTRUCTIONS - PROFESSORS: Please review this form. Complete or correct the sections, as applicable, from "Supervisor's Name" to "Ethics, safety, and training". Please sign and date near the bottom ("Supervisor's signature").

INSTRUCTIONS - STUDENTS: You may receive this form by email, or you may download it from www.mcgill.ca/science/research/ours/396/ after it has been posted. Either way, print and review this form. Complete or correct the sections, from "Student's Name" to "Student's Level", and sign ("Student signature). Ask your supervisor to sign her/his section near the bottom. Take it to the department corresponding to the course number; this may or may not be your own department. Do not register for a '396' course on Minerva until you receive departmental permission. Have a discussion with your supervisor about time/work expectations, keeping in mind that this is a 3-credit course (roughly, 10 hours per week for 12 weeks). Remember that a '396' course is an elective.

INSTRUCTIONS - DEPARTMENTS: After the unit chair/director/designate approves (or not) this project, please notify student. If approved, please give student permission to register on Minerva, and fax this form (with signatures) to the Office for Undergraduate Research in Science at 514-398-8102. The Office for Undergraduate Research in Science will later post the project online at https://mcgill.ca/science/research/ours/396/listing/, indicating whether the project is open for students to apply or taken.

QUESTIONS OR FEEDBACK? Contact Victor Chisholm by email, or phone 514-398-5964

Supervisor's Name: Dr. Maziar Divangahi

Supervisor's Email: maziar.divangahi [at] mcgill.ca

Supervisor's Phone: 514-398-3864 Ext.089727

Supervisor's Website: http://meakins.mcgill.ca/meakins/

Supervisor's department: Microbiology and Immunology

Course number: MIMM397 (Immunology

Term: Fall 2011-2012

Project start date: Wednesday, September 1, 2011

Project end date: Tuesday, December 6, 2011

Project title: Understanding the role of host lipid mediators during H1N1 infection

Project description: Despite the worldwide application of vaccination and other anti-viral interventions, influenza infection remains a persistent threat to humans. Intriguingly, most influenza-related death results from an uncontrolled host immune response rather than the cytopathic effects of the virus. Therefore, understanding the mechanisms of immune regulation during influenza virus infection, including the role of virulent influenza in altering such mechanisms, is critical to prevent the severe pathology and mortality associated with this virus.

The balance between host lipid mediators prostaglandin E2 (PGE2) and lipoxin A4 (LXA4) production is determinant toward the regulation of macrophages (M?) death program 1,2,3. Interestingly, the recent identification of a novel influenza pro-apoptotic protein called PB1-F2 and its role in induction of apoptosis, specifically in monocytes, highlights the critical link between M? apoptosis and susceptibility to influenza infection 4. Using bone marrow-derived M? from wild-type (WT) mice, mice unable to produce PGE2 (Pges-/-) and mice unable to produce LXA4 (5-LO-/-), we aim to investigate the regulatory role of these lipid mediators in the fate of M? during influenza infection. To do so, we will infect these cells with parental influenza virus and engineered mutant lacking pro-apoptotic PB1-F2 gene or expressing PB1-F2 from the pandemic 1918 influenza H1N1 strain. Assays will include the determination of apoptosis/necrosis ratio in M?, inflammatory cytokine and type I interferon production as well as reconstitution experiments by addition of exogenous PGE2 and LXA4. Data obtained through these various experiments are expected to guide in vivo studies on the correlates of M? death modality and susceptibility to influenza.

References

  1. Chen,M., Divangahi, M. et al. Lipid mediators in innate immunity against tuberculosis: opposing roles of PGE2 and LXA4 in the induction of macrophage death. J. Exp. Med. 205, 2791-2801 (2008).
  2. Divangahi,M. et al. Mycobacterium tuberculosis evades macrophage defenses by inhibiting plasma membrane repair. Nat. Immunol. 10, 899-906 (2009).
  3. Divangahi,M., Desjardins,D., Nunes-Alves,C., Remold,H.G., & Behar,S.M. Eicosanoid pathways regulate adaptive immunity to Mycobacterium tuberculosis. Nat. Immunol. 11, 751-758 (2010).
  4. McAuley,J.L. et al. Expression of the 1918 influenza A virus PB1-F2 enhances the pathogenesis of viral and secondary bacterial pneumonia. Cell Host. Microbe 2, 240-249 (2007).

Prerequisite: 1 term completed at McGill + CGPA of 3.0 or higher; or permission of instructor.

Grading scheme (The final report must be worth at least 50% of final grade): Final grade shall be based on laboratory performance as evaluated by the research supervisor (50%) and the final written research report (minimum 10 pages) graded by the supervisor and the course coordinator or the coordinator's delegate (50%).

Project status - This project is: Taken. The professor has no more '396' projects this term.

Ethics, safety, and training: Supervisors are responsible for the ethics and safety compliance of undergraduate students. Which of the following, if any, is involved? Animal subjects

Student's Name:

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