Investigation of P. aeruginosa clinical isolates leading to stronger inflammatory responses via activation of the p38 MAPK - MIMM 396 Undergraduate Research Project Application Form

Supervisor's Name: Simon Rousseau

Supervisor's Email: simon.rousseau [at] mcgill.ca

Supervisor's Phone: 098148

Supervisor's Website: http://simonrousseau-research.mcgill.ca

Supervisor's department: Medicine

Course number: MIMM 396 (Microbiology)

Term: Summer 2014

Project start date: Monday, May 5, 2014

Project end date: Friday, August 29, 2014

Project title: Investigation of P. aeruginosa clinical isolates leading to stronger inflammatory responses via activation of the p38 MAPK

Project description (50-100 words suggested): In CF patients, lung function declines and fails as a consequence of chronic bacterial infections and airway inflammation. A dominant pathological feature of CF lung disease is intense neutrophilic inflammation that is excessive to bacterial burden 1-3. Therefore, it is imperative to identify the molecular mechanisms underlying lung tissue destruction caused by this excessive inflammation. We found that p38 MAPK activity determines the magnitude of airway epithelial cell inflammatory responses to Pseudomonas aeruginosa, a gram-negative bacterium 4. We showed that certain mutations in P. aeruginosa leading to a mucoid phenotype, in addition to activating of TLR5, also engages TLR2 to stimulate more strongly p38 MAPK, and stimulate a more robust inflammatory response 5. We now want to determine whether this relationship between P. aeruginosa and stronger p38 MAPK activation leading to increased neutrophilic inflammation holds true in CF adult patients suffering from severe lung disease. In a study characterizing 51 CF adults at the Montreal Chest Institute, we showed that patients could be stratified in two groups based on circulating levels of calprotectin, an abundant neutrophil protein found during inflammation. Patients who had levels greater than 151 ng/ml had worst respiratory functions as measured by Forced Expiratory Volume at 1 sec % predicted (FEV1% of 43.2), when compared to patients who had levels of calprotectin < 151 ng/ml (FEV1% 72.4). This difference was statistically significant (p value < 0.0008). Interestingly, when the microbiology was investigated, the patients in the calprotecin high group were positive for mucoid PA 82% of the times compared to 32% in the other group.Therefore, during the summer of 2014, teh student will test the hypothesis that bacterial clinical isolates from patients with worst lung disease (calprotectin levels > 151 ng/ml) activate more potently p38 MAPK in a TLR2-dependent fashion.

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.

How students can apply / Next steps: After all parts of this application form are completed, and the hard copy is signed by the professor and the student, bring this application form and your unofficial transcript to Prof. Gregory Marczynski during office hours, who will review/approve as the course coordinator for MIMM 396 (Microbiology) or MIMM 397 (Immunology).

Ethics, safety, and training: Supervisors are responsible for the ethics and safety compliance of undergraduate students. This project involves: Human subjects; Biohazardous substances.