Prof. Laura Itzhaki - Group Leader
Professor of Structural Pharmacology
Newnham College
Member of the Naked Mole-Rat Initiative
Member of the CRUK Cambridge Centre
E-mail: lsi10@cam.ac.uk
Tel:+44 1223 334017
Fax:+44 1223 334100
Keywords
Tandem-repeat proteins, protein engineering, protein folding, protein design, protein-protein interactions, cancer therapeutics
Investigator biography
Research summary
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.
Lab Members
Dr Piyush Kumar Chaturbedy, Aurora Diamante, Zhen Du, Rohan Eapen, Harry King, Cynthia Okoye, Juliane Ripka, Dr Pam Rowling, Cameron Smith, Sian Stockton, Marie Synakewicz, Grasilda Zenkeviciute
Selected recent publications
Perez-Riba, A., Lowe, A.R., Main, E.R.G., Itzhaki, L.S. Context-dependent energetics of loop extensions in a family of tandem-repeat protein. Biophys. J.114: 2252 (2018).
Guttenplan, A.P.M., Young, L.J., Matak-Vinkovic, D., Kaminski, C.F., Knowles, T.P.J., Itzhaki, L.S. Nanoscale click-reactive scaffolds from peptide self-assembly. J. Nanobiotech. 5: 70 (2017).
Xu, W., Lau, Y.H., Fischer, G., Tang Y.S., Chattopadhyay, A., de la Roche, M., Hyvonen, M., Verma, C., Spring, D.R., Itzhaki, L.S. Macrocyclized extended peptides: Inhibiting the substrate-recognition domain of tankyrase. J. Am. Chem. Soc. 139: 2245 (2017).
Hutton, R.D., Wilkinson, J., Faccin, M., Sivertsson, E.M., Pelizola, A., Lowe, A.R., Bruscolini, P. Itzhaki, L.S. Mapping the topography of a protein energy landscape. J. Am. Chem. Soc. 137: 14610 (2016).
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).
Funding
