Recognition and Cleavage of Biological Phosphates
Molecular Recognition, Mechanism and Biomedical Applications
This Marie Curie network was set up to provide young researchers with hands-on research experience and formal training in the classically separate disciplines of Chemistry and Biology.
It is fully funded by the European Union (project number FP7-MC-ITN-2009-238679).
Research in this network is centred around understanding the central biological process of phosphate transfer and combines experts in synthetic chemistry, enzyme model building, kinetic analysis, protein chemistry and directed evolution in a concerted effort to gain a quantitative understanding of transition states that are key to understanding how biological systems can achieve phosphate transfer with unrivalled efficiency. Efficiency is also key for drugs, prodrugs or drug delivery reagents that target phosphate bonds.
Training in this area is highly interdisciplinary in nature requiring a joint effort of chemists and biologists centred around mechanistic thinking, which is at the core of the workshops and accompanying training measured offered. The quantitative language (i.e. kinetic and molecular recognition studies) used to describe and improve natural systems unites all participants and provides the theme for our training programme on analysis of phosphate transfer catalysis and recognition. The training programme builds on a previous Marie-Curie initiative, ENDEVAN, coordinated by Prof. A. J. Kirby FRS.
Technology Transfer. Research and training in this area strongly interface basic research with industrial applications. Ultimately our understanding of this central bio-reaction should lead to useful applications on the long term, e.g. as artificial nucleases, with potential roles in gene regulation, if efficient catalysis can be combined with selective recognition. This proposal is part of a long-term strategy aimed at developing reagents which act by binding or catalytically (thus as artificial enzymes) to interfere with the expression of specific genes. This can be achieved through selective binding eventually (but not necessarily) followed by cleaving the nucleic acid backbone. Crucially for therapeutic success these reagents have to be delivered into the cell, which is why delivery issues are also addressed. The incorporation of industrial partners (one SME, one larger company) ensures that the full life-span of drug development is covered in this training programme – and may provide a conduit for utilising and marketing the results of this collaborative programme.
The network is composed of the following units
|#||unit name||Principal Investigator||Affiliation|
|01||UCAM||Dr Florian Hollfelder||Dept of Biochemistry, University of Cambridge|
|02||UPAD||Prof Paolo Scrimin||Dept of Chemical Sciences, University of Padua|
|3A||KI||Prof Roger Stromberg||Dept of Organic and Bioorganic Chemistry, Karolinska Institutet|
|3B||KI||Prof Edvard Smith||Dept of Molecular Genetics, Karolinska Institutet|
|04||UT||Prof Harri Lönnberg||Dept of Chemistry, Turun Yliopisto|
|05||USFD||Prof Nick Williams||Dept of Chemistry, University of Sheffield|
|06||UGENT||Prof Dr Annemieke Madder||Dept of Organic Chemistry, Universiteit Gent|
|09||JWGU||Prof Dr Michael Göbel||Dept of Organic Chemistry and Chemical Biology, Goethe-Universitaet Frankfurt|
The marie Curie Fellows Association integrates MC fellows and associated researchers. It is is the common platform for the MC researchers to network, discuss research, career prospects, get news updates about conferences, events and many other interactive sessions.
- © 2011-2013 Florian Hollfelder, University of Cambridge