cihr_grants: 163307
This data as json
| external_id | title | project_lead_name | co_researchers | institution | province | country | competition_year | award_amount | program | program_type | theme | research_subject | keywords | abstract | duration | source_url |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 163307 | The Biomechanics of Skin Blistering Diseases: A Cellular and Biophysical Approach. | Fudge Douglas S | Fudge, Douglas S | University of Guelph | Ontario | Canada | 200802 | 90322.0 | Catalyst Grant: Skin Diseases and Conditions | Operating Grants | Biomedical | Musculoskeletal Health and Arthritis | Biomechanics; Biophysics; Epidermolysis Bullosa Simplex; Intermediate Filaments; Keratin; Skin | Epidermolysis Bullosa Simplex (EB) is a genetic disease characterized by blistering or erosion of the skin. Here we propose to study the physical basis and mechanisms of this disease. Mutations in a variety of structural proteins in skin can give rise to EB, but it is not known exactly how these defects weaken the skin. This proposal focuses on two components of skin cells that have been implicated in EB - keratin intermediate filaments (IF) and desmosomes. Keratin IFs are protein filaments that form a dense network in the cytoplasm and are believed to impart cells with mechanical strength. Mutations in keratin IF genes have been shown to lead to a form of EB known as EB Simplex (EBS). In EBS patients, the IF network in skin cells is defective, which is believed to make them mechanically fragile. Of course a network of keratin IFs alone does not guarantee mechanical strength - the filaments must be anchored to structures that are equally strong. Indeed, IFs are anchored in spot-weld like structures called desmosomes. Together, IFs and desmosomes link skin cells into a tough mechanical continuum. We will conduct two kinds of experiments using both wild type cells and cells expressing mutant keratin IF and desmosomal proteins. In the first, we will mechanically deform skin cells that are adhered to a deformable substrate and assess the effects on cell viability and the structure of the IF network. In the second set of experiments, we will investigate the biomechanics of wild type and mutant IFs using purified IFs. The results of these experiments will provide new insights into the mechanical function of IFs and desmosomes in skin, and the mechanisms by which defects in these structures can lead to human disease. They will also help us develop an in vitro model that we can use to evaluate the efficacy of potential treatments for this debilitating disease. | 1 yr 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=163307&lang=en |