Department of Cell and Molecular Biology

Research projects

Life processes depend critically on interactions between macromolecules. These interactions often involve coupled folding and binding, which lies at the heart of many biologically, medically, and technologically important processes and phenomena.

Research in my group focuses on three different systems that involve coupled binding and folding. Many pathogenic bacteria use hair-like structures called fimbriae to attach to host cells and initiate infection. The assembly of adhesive fimbriae via the chaperone/usher pathway provides an elegant example of how protein folding by Nature’s design may be coupled to binding in order to gain control over a complex assembly and secretion process. Spider silks, assembled in a complex process that links folding to polymerization, have extraordinary mechanical properties that make them attractive for development of novel materials. BRICHOS domains are used by mammalian cells to manage the problems associated with aggregation-prone peptides that must be partitioned away from amyloidogenic and potentially harmful pathways into biologically meaningful ones. Understanding how BRICHOS domains inhibit formation of toxic amyloid intermediates at the molecular level can pave the way for new ways of treating amyloid diseases such as Alzheimer’s disease, Parkinson’s disease, and type 2 diabetes.

We study these examples of coupled folding and binding using a powerful combination of X-ray crystallography and other diffraction-based techniques (SAXS, fibre diffraction) with molecular biology, biophysical, biochemical, and computational techniques. The knowledge generated from these studies will shed light on fundamental questions important for many biological processes. Such knowledge can also be used in the development of novel applications in medicine (e.g. novel ways for treating amyloid diseases and bacterial infections) and biotechnology (e.g. novel spider silk-based materials).