Research Bursary Program

Supervisor Project Proposal (Summer 2015)

Supervisor Last Name: Li / Supervisor First Name: Nicole Yee-Key
McGill Dept/School: Faculty of Medicine
Faculty Professor (Full, Associate or Assistant): Assistant Professor
Email: / Phone No. (optional):
Research Field: laryngeal injury and repair / Proposal No. (1 or 2): 1
Research Location (McGill or affiliated institution): McGill University
Ethics approval will be required for proposed project (Yes/No): No
Proposed project will involve chart reviews (Yes/No): No

Project Title(maximum 1 line): Effects of extracellular matrix and phonation on vocal fold cells

Hypothesis/Question to be Addressed(maximum 4 lines):

Voice problems constitute the most common communication disorder across the lifespan, with direct health costs a minimum of $1.75 billion/ year in Canada. This project seeks to advance the science of voice restoration.

The extracellular matrix (ECM) is a natural scaffold that provides structural support to cells in living tissue. When cells interact with the surrounding ECM, they sense and react to changes in their physical environment. One working hypothesis is that ECM stiffening contributes to the scarring process. The temporal changes of ECM stiffness activate a profibrotic positive feedback loop between ECM and neighboring cells during tissue repair, which exacerbate the scarring outcome.

In addition to ECM stiffness, the effects of mechanical deformation on vocal fold cell activities will be investigated in this project. During speech and singing, the vocal folds deform in wave motion (i.e., oscillation) at high frequencies ranging from 20 Hz to 3 kHz. An existing vocal fold bioreactor will be used to generate phonation-like mechanical stimulation to synthetic vocal fold replicas. Cells will be cultured in the bioreactor for long-term phonatory loading.

Specific Aims(maximum 10 lines):

(1)Evaluate the influence of the extracellular matrix environment on vocal fold cells. Cells react to changes in their physical environment, such as matrix stiffening during tissue repair. We will investigate the short-term and long-term effects of matrix stiffening on vocal fold cell motility, proliferation, viability, cytokine protein expression, and the volume of collagen fibers, using a stiffness-tunable synthetic scaffold.

(2) Evaluate the influence of phonation on vocal fold cells. In addition to matrix stiffening, mechanical deformation affects cell activities in tissue growth and pathology. The vocal folds deform at high frequencies during speech. Dr. Li will use an existing vocal fold bioreactor to generate phonation-like mechanical stimulation to vocal fold cells grown in scaffolds. Cellular activities related to inflammation and repair will then be investigated in this in vitro model system.

Role of Student(maximum 15 lines):

The student will be responsible for:

1)Literature search

2)Help for cell culturing

3)Help for cell and protein data collection and analysis

4)General housekeeping of laboratory

Interested students are invited to send a cover letter andtheir Curriculum Vitae to Dr. Li (see contact information above).