'Role of fibronectin in the biogenesis and function of microfibrils in vivo' - ANAT 396 Undergraduate Research Project Application Form

Supervisor's Name: Dieter Reinhardt

Supervisor's Email: dieter.reinhardt [at] mcgill.ca

Supervisor's Phone: 514-398-4243

Supervisor's Website: http://reinhardt-lab.mcgill.ca

Supervisor's department: Anatomy and Cell Biology

Course number: ANAT 396 (Anatomy and Cell Biology)

Term: Fall 2013-2014

Project start date: Tuesday, September 3, 2013

Project end date: Tuesday, December 15, 2013
The last day of classes is December 3. December 15 falls during the final exam period. The Faculty of Science allows courses to end during the final exam period, as long as submissions can be reviewed and grades submitted by the appropriate deadline, and also that the workload required to complete the project not exceed that normally required to prepare for final examinations.

Project title: Role of fibronectin in the biogenesis and function of microfibrils in vivo

Project description (50-100 words suggested): Fibrillins are protein components of connective tissue fibers called microfibrils, which are ubiquitously distributed in most tissues including cardiovascular and pulmonary tissues. Mutations in fibrillins give rise to a number of heritable connective tissue disorders summarized as fibrillinopathies. These include Marfan syndrome, acromelic dysplasias, dominant Weill-Marchesani syndrome, stiff skin syndrome and others, with a combined prevalence of ~1 in 3,000. Immense inter- and intra-familial variability is a common feature of all fibrillinopathies, suggesting that other gene products play modifying roles in the disease pathogenesis. Full appreciation of pathogenetic mechanisms resulting in fibrillinopathies requires detailed understanding of fibrillin and microfibril biogenesis and function. We have demonstrated in published cell culture studies that another extracellular protein, fibronectin (FN), acts as an organizer of microfibril formation and function. Based on this finding, modified interactions between FN and mutant fibrillin in patients could be associated with disease pathogenesis. In this project, we aim to determine the role of FN on the formation, homeostasis and function of microfibrils in vivo. Since FN null mice are early embryonic lethal, we generated a conditional and tamoxifen-inducible FN knockout mouse model. In this model, FN can be deleted in smooth muscle cells at any given time point by injection of tamoxifen. Preliminary results demonstrate disorganized blood vessel walls, and enlarged airspaces in the lung after tamoxifen-induced FN deletion. The student will work on the analysis of the phenotype of this mouse model. The student will inject mice with tamoxifen, perform genotyping using various PCR techniques, prepare tissues, perform histological and immunohistological analyses, extract proteins from tissues and quantify them by Western blotting. The student will further work on data analysis and interpretation.

Prerequisite: 1 term completed at McGill + CGPA of 3.5 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 (50%)

Project status: This project is taken.

(How students can apply: Bring a printed copy of this application form and your advising transcript to me during office hours.)

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