Principal Investigator: Derek Logan

The extracellular matrix (ECM) provides the structural and biomechanical properties crucial for tissue function. ECM interactions and signals transmitted via cellular receptors control many aspects of cellular life, for instance proliferation, differentiation, maintenance of differentiation state and survival. Individual components of the ECM are produced locally and secreted into the environment, where they spontaneously assemble into well-organized networks with different properties. The ECM is continuously modified by the resident cells and adapted to changes in the environment. In diseases such as osteoarthritis (OA) and atherosclerosis, the balance between degradation and synthesis of the ECM is disturbed. Understanding the molecular basis for the interactions controlling ECM assembly, particularly at a structural level, is critical for understanding ECM turnover and homeostasis under normal conditions, as well as in diseases such as OA and rheumatoid arthritis, which affect a large proportion of the population. At present only very limited structural information is available on the structural basis for the molecular interactions underlying the genesis and maintenance of ECM networks.

At present we are principally interested in:

1) The polyvalent interactions of the C-type lectin domain of the lectican family in protein-protein and protein-carbohydrate interactions
2) The structural basis for the function of the small leucine-rich repeat protein chondroadherin and its role in osteoarthritis
3) Structural explanations for the function of the fibulins, which consist mainly of calcium-binding EGF repeats and which have recently been implicated in various types of cancer.

Collaborators:
Prof. Dick Heinegård, Dpet. of Connective Tissue Biology, Biomedical Center, Lund University
Dr. Anders Aspberg, Institute of Molecular Biology and Physiology, Copenhagen University, Denmark