'Identification and characterization of the ENU-induced mutation, Grisou.' 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. 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, 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.
QUESTIONS OR FEEDBACK? Contact Victor Chisholm by email, or phone 514-398-5964.
Name: Vidal, Silvia
Email: silvia.vidal [at] mcgill.ca (silvia dot vidal at mcgill dot ca)
Phone: 5143982362
Supervisor's department: Microbiology and Immunology
Supervisor's department (if none of the above)  
Course number: MIMM396 (Microbiology)
Term: Winter 2010-2011
Project start date: Janurary 4, 2011
Project end date: April 8, 2011
Project title: Identification and characterization of the ENU-induced mutation, Grisou.
Project description: Background and rationale: The identification of the genetic basis underlying deficits in immune cell compartments or functions in mice has provided an invaluable tool to understand fundamental mechanisms of immune homeostasis and host response against malignancies and infection. For example, the gene encoding the transcription factor Foxn1 directing thymus development was found to be mutated in nude mice, which have a severe T cell deficiency. Further, the human orthologous gene (FOXN1 ) was found to be mutated in severely immunodeficient patients patients with an absent tymus . However, limiting factors to this approach include the fact that only a finite number of inbred strains with limited genetic variation are available. Chemical (ENU) mutagenesis, a method that has been successfully applied to the study of several different model organisms (bacteria, Caenorhabditis elegans, Zebrafish, Drosophila melanogaster), is an innovative approach to the study the mouse immune system. Furthermore, ENU mutagenesis creates random point mutations throughout the genome, representing an unbiased method for identifying novel physiologic pathways (for which little biochemical or genetic information is available) since no assumptions are made about the relevant genes.
Previous work: A mouse ENU screen has been initiated at the Life Sciences Complex, leading to the identification of several new mouse models. Among them, Grisou, was identified based on a phenotype involving coat color, splenomegaly and abnormal lymphocyte counts. Genetic mapping localized the mutation to the central region of chromosome 10.
Hypothesis: We hypothesize that a single mutation involved in lymphocyte development or function underlies the phenotype observed in Grisou mice.
Objectives: Our main objective is to identify the Grisou mutation, provide a detailed immunophenotypic characterization, and ultimately probe the mutation in the host response to infection.
Specific aims: 1) Narrow down the Grisou genetic interval using single nucleotide polymorphism analysis for four new chromosome 10 markers in a small population (N = 24) segregating the coat color phenotype. 2) Identify candidate genes within the Grisou critical interval using bioinformatic analysis and publicly available mouse genome sequence. 3) Identify putative ENU-mutations by sequencing exons (and their flanking sequences) of the strongest candidate genes. 5) Enumerate immune cell populations in spleen and peripheral ganglia using specific antibodies against NKT, NK, T, B lymphocytes, macrophages, neutrophils, dendritic cells and mast cells. 6) Based on the gene mutation and cell deficit, probe the influence of gene mutations in the host response to infection with DNA, positive and negative stranded RNA viruses.
Expected results and significance: We expect to identify a single ENU-induced mutation in the Grisou interval, which will be associated with a specific immune cell deficit and host susceptibility to infection. This knowledge should enhance our understanding of normal immune functions.
Prerequisite: 1 term completed at McGill + CGPA of 3.0 or higher; or permission of instructor.
Other prerequisite, if applicable:  
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%).
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: