Dr Laura Itzhaki - Group Leader
Tel:+44 1223 334017
Fax:+44 1223 334100
Tandem-repeat proteins, protein engineering, protein folding, protein design, protein-protein interactions, cancer therapeutics
Our research focuses on a class of proteins with very distinctive architectures, known as tandem-repeat proteins. Our group and others have shown that the simple modular, one-dimensional architecture of tandem repeat proteins gives them distinctive properties compared with globular proteins and makes it uniquely straightforward to map the energetics of their structures and to rationally redesign their stability, folding and molecular recognition. This class of proteins is thus an exceptionally sensitive and versatile tool that we are now exploiting to dissect otherwise intractable cellular mechanisms. We are focusing on ankyrin, HEAT and ARM repeat proteins that play important roles in disease, in particular cancer, and we are using the insights we obtain to develop therapeutic strategies for targeting them; we are also exploring how to exploit the extraordinary design-ability of these proteins for biomedical and biotechnology applications.
Tsytlonok, M., S. M. Ibrahim, P. Rowling, W. Xu, M. J. Ruedas-Rama, A. Orte, D. Klenerman, and L. Itzhaki. Single-molecule FRET reveals hidden complexity in a protein energy landscape. Structure, 23(1): 190 – 198 (2015).
Rowling, P.J.E., Cook, R., Itzhaki, L.S. Towards classification of BRCA1 missense variants using a biophysical approach. J. Biol. Chem. 285: 20080-7 (2010).
Werbeck, N.D., Rowling, P.J., Chellamuthu, V.R., Itzhaki, L.S. Shifting transition states in the unfolding of a large ankyrin repeat protein. Proc. Natl. Acad. Sci. USA 105: 9982-7 (2008).
Lowe, A.R., Itzhaki, L.S. Rational redesign of the folding pathway of a modular protein. Proc. Natl. Acad. Sci. USA 104: 2679-84 (2007).