Objective
The calcium signal is involved in cell cycle and cell differentiation. It is deciphered through the binding to calcium binding proteins. Upon calcium binding, the proteins undergo conformational changes and interact with specific target enzymes or supramolecular complexes.
Calmodulin (CaM) will be studied in particular as the prototypical calcium binding protein by using recombinant proteins with different electrostatic potentials. Molecular chaperons such as heat shock protein hsp 90 seem to interact with CaM and this new calcium signal transduction regulation will be considered. Moreover, Ca and Ca-calmodulin complex play a fundamental role in the microtubular system formation through a calcium dependent assembly-disassembly process.
To understand the transduction of the quantitative calcium signal into the qualitative cellular response, research in the project will focus on the calmodulin/calcium/peptide complexes with synthetic peptides derived from the calmodulin binding domain of calmodulin target proteins. Besides classical biophysical methods (fluorescence, CD, direct binding by flow dialysism), the thermodynamic characterisation of the systems by isothermal and scanning microcalorimetry will be investigated.
In addition, knowledge will be gained on the structural and thermodynamic characterisation of these complexes and such studies will be the starting point for the design and screening of new classes of more specific calmodulin inhibitors. In return, these inhibitors will be valuable tools to analyse the role of the CaM/hsp 90 interaction in vivo and to settle the controversy over the role of calmodulin in the regulation of the microtubular system.
Topic(s)
Call for proposal
Data not availableFunding Scheme
Data not availableCoordinator
13385 Marseille
France