Undergraduate Research Project Application Form

INSTRUCTIONS - PROFESSORS: Fill out Sections A & B then submit this form online. (You will receive an email copy of the form. The Office for Undergraduate Research in Science will also post the project online, indicating whether the project is open for students to apply or taken.) DONE

INSTRUCTIONS - STUDENTS: You may receive this form by email, or you may download it after it has been posted. Either way, print this form. Complete and sign Section C on the hardcopy. Ask your supervisor to sign Section D. Take it to the department corresponding to the course number in Section A (this may or may not be your own department). Do not register for a '396' course on Minerva until you receive departmental permission.

INSTRUCTIONS - DEPARTMENTS: After the unit chair/director/designate approves (or not) this project, 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.

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

Name: Dr. Nahum Sonenberg
Email: nahum.sonenberg [at] mcgill.ca (nahum.sonenberg) -at-mcgill.ca
Phone: 514 398 7274
Supervisor's department: Biochemistry
Supervisor's department (if none of the above)  
Course number: ANAT396 (Anatomy and Cell Biology)
Term: Winter 2008-2009
Project start date: January 5, 2009
Project end date: April 30, 2009
Project title: Role of 4E-BP1/2 in the Progression of Leishmania Infection
Project description: The parasitic protozoan Leishmania, the causative agent of leishmaniasis, is an obligate intracellular pathogen that inhabits the macrophages. Although, it is well documented that Leishmania suppresses several cellular functions, such as gene expression and phosphorylation, it is currently not known the role of translational control in Leishmania infection. Translational control of gene expression provides the cell with a rapid response to external triggers or cues. In eukaryotes, translational control mostly occurs at the rate-limiting initiation step, during which the small 40S ribosomal subunit is recruited to the mRNA, a process which is facilitated by the cap structure. The cap structure is recognized by eukaryotic initiation factor 4F (eIF4F), which consists of eIF4E, the cap-binding subunit, eIF4A, a bidirectional RNA helicase, and eIF4GI or eIF4GII, scaffolding Proteins. eIF4F complex assembly is inhibited by the translational repressors 4E-binding proteins (BPs) mTOR-mediated phosphorylation of 4E-BPI (the best characterized 4E-BP) stimulates translation by dissociating 4E-BPs from eTF4F. Hypophosphorylated 4E-BPI has an opposite effect.
Since Leishmania has developed several strategies to hijack the cellular machinery, we wished to study the role of 4E-BPs in this parasitic infection. We found that Leishmania induces dephosphorylation of 4E-BP 1 in macrophages. Interestingly, this event requires the activation of host tyrosine phosphatases (PTPs), which in turn mediate Leishmania-dependent inhibition of microbicidal and immunogenic molecules.
In addition, genetically susceptible Balb/C mice either carrying (wild type - WT) or lacking (double knock out - DKO) the 4e-bp1 and 4e-bp2 genes were infected in the footpad with Leishmania major. Interestingly, 4E-BP 1/2 DKO mice were less susceptible to the infection than their WT littermates, as revealed by a dramatic reduction in the inflammation and the size of lesion in the footpad. Consistent with these data, the parasitic load in the footpad and the adjacent lymph nodes was reduced in the 4E-BPI/2 DKO mice. Remarkably, only in WT mice the parasite was able to migrate to the spleen. Our data support the notion that the 4E-BPs are key factors for the development of the disease. Currently, we are investigating the molecular mechanisms underlying these processes.
Prerequisite: 1 term completed at McGill + CGPA ≥ 3.0; or permission of instructor.
Other prerequisite, if applicable:  
Grading scheme (The final report must be worth at least 50% of final grade): 50% on lab performance, 50% on Final Report
Other project information:  
Project status - This project is: Taken. The professor has no more '396' projects this term.
How students can apply: N/A; this project is filled.
If other, please specify:  
Ethics, safety, and training
Which of the following, if any, is involved? One or more of the following
Animal subjects [x]
Human subjects [ ]
Biohazardous substances [x]
Radioactive materials [ ]
Handling chemicals [x]
Using lasers [ ]
Supervisors are responsible for the ethics and safety compliance of undergraduate students.
Do not complete this section unless/until the student is identified.
McGill ID:  
Email (first.last [at] mail.mcgill.ca):  
Program (E.g., B.Sc. Maj. Chem. Min. Biol.):  
Level (U0 / U1 / U2 / U3):  
Student signature - I have not applied for another '396' course in this term:  
Do not complete this section unless/until the student is identified.
Supervisor: I give my permission for the student identified in section C to register for this project under my supervision.
Supervisor's signature:  
Unit chair/director/designate: I certify that this project conforms to departmental requirements for 396 courses.
Unit chair/director/designate's name:  
Unit chair/director/designate's signature: