Work Packages - Objectives
WP1 - Design, synthesis and isolation from marine microorganisms of small molecule mimetics of neurotrophins
Synthesis of focused libraries of novel 17-spiro-neurosteroid derivatives. Hit identification and hit to lead optimisation of UNICAEN compound library. Isolation of natural products from marine fungi and bacteria of the Mediterranean basin. Establishment of Structure-Activity-Relationships for selective activity for TrkA, TrkB, TrkC and p75NTR receptors. Application of ligand-based and receptor-based drug design approaches for optimisation and in silico methodologies for ADMET profiling. Production of purified targets and x-ray crystal structure determination of target-ligand complexes.
WP2 - In vitro assays, study of the underlying molecular mechanisms
In vitro evaluation of the biological functions and the underlying molecular mechanisms of synthetic and natural compounds in relation to neurotrophin receptors (TrkA, TrkB, TrkC and p75NTR) as well as determination of the ADMET properties of the active compounds. Both cellular assays as well as biomolecular NMR approaches will be employed.
WP3 - In vivo studies
WP3 will enable the in vivo brain uptake and evaluation in animal models of AD, MS and MND of selected synthetic and natural compounds, exhibiting potent activity against neurotrophin receptors while being devoid of in vitro toxicity. Furthermore neuroproteomics will unveil their effect on synapse proteome and density.
WP4 - Scientific and industrial training activities
The objective of WP4 is to provide a comprehensive and multidisciplinary research and industrial training to ESRs to contribute to their formation as the future European experts in the neurotrophin field.
WP5 - Dissemination and public engagement
Definition and implementation of a strategy for the dissemination and the promotion of the objectives and results of EuroNeurotrophin to the research community, relevant industry and public stakeholders, schools, wider public and press.
WP6 - Exploitation
WP6 aims to ensure appropriate and efficient exploitation of the intellectual property emanating from the project results.
WP7 - Coordination and project management
The objective of WP7 is to ensure a transparent and effective management of scientific, training, financial and administrative issues.