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'Analysis of the Functions of Deubiquitinase USP21 in the Toll-like Receptor and TNFα Receptor Signaling' - PHGY 396 Undergraduate Research Project Application Form.

INSTRUCTIONS - PROFESSORS: Please print and 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 after it has been posted here. 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 in Section A; this may or may not be your own department. (* EXCEPTIONS: For NSCI 396 and COGS 396, please bring it to the Interdisciplinary Programs Adviser in Dawson Hall.) 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 send a copy of this form (with signatures) to the Office for Undergraduate Research in Science (either fax, or internal mail to Dawson Hall 408-A, or PDF scan + email).

QUESTIONS OR FEEDBACK? Contact the Office for Undergraduate Research in Science.

Supervisor's Name: Dr. Ana Nijnik (Nyzhnyk)

Supervisor's Email: anastasiya [dot] nyzhnyk [at] mcgill [dot] ca

Supervisor's Phone: 514-398-5567

Supervisor's Website:  www.mcgill.ca/complextraits/scientists/anastasia-nijnik

Supervisor's department: Physiology

Course number: PHGY396 (Physiology)

Term: Winter 2012-2013

Project start date: January 7, 2013

Project end date: April 16, 2013

Project title: Analysis of the Functions of Deubiquitinase USP21 in the Toll-like Receptor and TNFα Receptor Signaling

Project description: USP21 is a poorly characterized member of the ubiquitin-spccific protease family, previously implicated in the deubiquitination of histone H2A and also of cytosolic kinase RIP1 involved in the signal transduction pathways downstream of TNFα receptor (TNFR). These studies relied on over-expression and knockdown of Usp21 in transformed epithelial cell lines. We have recently generated a novel Usp21-knockout mouse line. In this work the mouse line will be used to test the requirement ofUsp21 in the RIP1-dependent signaling pathways of the innate immune system in macrophagcs and dendritic cells (DCs). Wild type and knockout macrophages and DCs will be generated from the bone marrow of the mice, and stimulated in vitro with TNFα and a range of Toll-like receptor ligands. Cell responses to the stimulation will be monitored by measuring the inflammatory cytokine production by ELISA and the expression of activation markers by flow cytometry, and comparing wild type and knockout cells. If USP21 acts to deubiquitinate RIP1 in these cell types, we predict to see enhanced responses to stimulation in the knockout as compared to wild type cells. To analyze the signaling mechanisms responsible for any differences between the wild type and knockout cells, RIP1 ubiquitination levels and NFαB pathway activation may be compared by Western blotting. This work will address the role of Usp21 as in the critical signaling pathways of the innate immune system that protect us against infections but also mediate the pathology of many inflammatory diseases.

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): Performance in the lab during the course = 50%, Final Report = 50%.

Project status: This project is taken. The professor has no more posititions available this term.

How students can apply: This project is taken.

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

Student's Name:

Student's McGill ID:

Student's McGill Email:

Student's Phone:

Student's Program:

Student's Level (U0 / U1 / U2 / U3):

Student's signature - I certify that this course is with a different supervisor and on a different topic than any previous '396' course I have taken. I have not applied for another '396' course in this term:

Supervisor's signature - I give my permission for the student identified above to register for this project under my supervision:


Unit chair/director/designate's name:

Unit chair/director/designate's signature - I certify that this project conforms to departmental requirements for 396 courses: