Knight lab

Using a powerful combination of X-ray crystallography, molecular biology, and biophysical, biochemical, and computational techniques, we study how proteins and peptides bind to each other to form fibrillar structures such as spider silk, bacterial adhesive fimbriae, or amyloid. Our studies lay the foundation for further work to develop novel applications in medicine (e.g. novel ways for treating bacterial infections or amyloid diseases such as Alzheimer’s disease, Parkinson’s disease, and type 2 diabetes) and biotechnology (e.g. novel spider silk-based materials).

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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).

Group members

Research leader: Stefan Knight

People

Professor Stefan D. Knight

Telephone: +46 18 471 4554
fax: +46 18 530 396
e-mail: stefan.knight@icm.uu.se

Wangshu Jiang

Former group members

  • Devapriya Choudhury (PhD student) (now at JNU, New Dehli)
  • Jenny Mackenzie (nee Berglund) (PhD student) (now at Axis-Shield PoC AS, Oslo)
  • Anton Zavialov (postdoc, assistant professor) (now at University of Turku, JBL, Turku)
  • Anatoly Dubnovitsky (postdoc) (now at Karolinska Institutet, Stockholm)
  • Glareh Askarieh (PhD student) (now at Medivir AB, Stockholm)
  • Yu Xiaodi (“Dee") (PhD student) (now at The Scripps Research Institute, Boston)
  • Wimal Ubhayasekera (senior scientist)

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