Type XI collagen isoforms in skeletal biology

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DESCRIPTION (provided by applicant): Candidate: Dr. Julia Oxford has recently received an appointment to a tenure track position at Boise State University. She is trained in protein biochemistry and utilizes bioinformatic tools in her research on extracellular matrix molecules in development and disease. Environment: Boise State University has a commitment to the career development of faculty in scientific research and also the training of students by faculty who are actively carrying out research using current technologes. The University recognizes the importance of the inclusion of bioinformatics for genomics and proteomics research and training and strongly supports these, demonstrated by the recent NIH BRIN grant application. Research project: Type XI collagen is an integral component of the collagen fibrils of cartilage. The heterotypic fibrillar assembly functions with the proteoglycan component of cartilage to provide the necessary biomechanical properties during development, growth and as adult articular cartilage. This research aims to determine the mechanism by which type XI collagen plays a role in extracellular matrix assembly and maintenance of tissue integrity. To date, the effect of regulated fibril growth attributed to type XI collagen has been explained by steric hindrance by the amino propeptides on the surface of collagen fibrils. The actual mechanism is likely to be more complex. The proposed efforts are designed to test the hypothesis that isoforms of an I (XI) collagen modulate fibril diameter and that the amino terminal domain is involved in molecular interactions with other components of the extracellular matrix that mediate matrix assembly and tissue integrity. The cc I (XI) chain may have additional functions; the expression of a specific isoform may indicate the fate of cartilage (i.e. permanent cartilage or to become bone). Understanding the mechanism of type X1 collagen function has relevance to regulated matrix assembly and organization. This information could facilitate the rational design of therapeutic agents with the potential to modulate excessive collagen deposition and poor organization of collagen fibrils characteristic of fibrosis, a problem in major organs such as the heart, kidney, liver, lung, eye, blood vessels and skin. The ability to modulate the assembly of the extracellular matrix could be of great significance in the field of tissue engineering as well. Research career development plan: The immediate career goal is to establish a productive research laboratory that will make significant contribution to the field of extracellular matrix in development and disease. The long term goal is to integrate research and teaching efforts, with focus on musculoskeletal disease and development. The emphasis on molecular interactions will utilize protein biochemistry, tissue culture and molecular biology. Dr. Oxford will receive necessary training, including the responsible conduct of research, to support the research effort and to teach students these methods in an academic setting.