Imperial College London


Faculty of Natural SciencesDepartment of Life Sciences

Reader in Cell Cycle Control



+44 (0)20 7594 5302d.mann




605Sir Ernst Chain BuildingSouth Kensington Campus





Our lab is focused on using modern chemical biological techniques to probe biological function.  To this end, we have developed a novel screening platform (quantitative irreversible tethering, qIT) to identify chemical fragments that specifically and covalently bind to a given protein.  This method allows us to rapidly identify compounds that can act as starting points for the development of selective biological probes and potential therapeutics for a given target protein.

Figure 1Figure 1: Overview of quantitative irreversible tethering.

We have extensively validated the qIT methodology using the cell cycle regulatory kinase cyclin-dependent kinase 2 (cdk2) demonstrating hit identification and subsequent use of covalent determining structure/activity relationships to improve hit selectivity.  We are currently pursuing a range of targets in the oncology space using qIT. 


Figure 2: Development of covalent structure/activity relationships (covSAR) developed against a cdk2 model.

In addition, we have a long-standing interest in the determination of the substrates of protein kinases.  These enzymes are key regulators of almost all eukaryotic processes but substrate identification is difficult: there are over 500 kinases encoded by the human genome, each performing the same biological transformation on a range of overlapping protein substrates.  We are currently exploring the incorporation of non-natural amino acids into protein kinases to enable crosslinking of kinase and substrate with subsequent substrate purification and proteomic identification.


Eiji Hara, Division of Cancer Biology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo

Paivi Ojala, Univerisity of Helsinki

Kwee Yong, UCL Cancer Centre

Michal Optyeka, University of Palacky

Richard Bishop, International Livestock Research Institute, Nairobi

Prof Mauricio Barahona, Maths, Imperial College London

Prof Alan Armstrong, Chemistry, Imperial College London

Prof Ramon Vilar, Chemistry, Imperial College London

Dr Rudiger Woscholski, Chemistry, Imperial College London

Prof David Klug, Chemistry, Imperial College London

Prof Sophia Yaliraki, Chemistry, Imperial College London

Dr Ed Tate, Chemistry, Imperial College London