Neurocypres participants introductions
This page offers a short discription of the activities of the participants of the Neurocypres project for the interested non-scientists.
Introduction from VU University (I. de Esch)
The Medicinal Chemistry group at the VU University Amsterdam comprises two subgroups; a pharmacology group which focuses mainly on GPCR’s and a structure based drug design group, the latter is involved in the Neurocypres project. For the Neurocypres project a fragment based drug discovery strategy is applied to design new small molecules as ligands for the human 5-HT3A receptor. Several different areas of fragment based drug discovery are touched upon these include high throughput screening, homology modelling and multiple aspects of organic chemistry. Read more >
Introduction from Beatica (H. Danielson)
The role of Beactica in Neurocypres is to characterize ligand binding to Cys-Loop Receptors (CLR) using SPR biosensor technology, enabling a more accurate description of the ligand-binding event. The Sprint™ drug discovery platform will be used to identify novel ligands for Cys-Loop Receptors. Sprint™ offers a fast route for generating optimal starting conditions and development routes in the search for new lead compounds towards any protein target. The details of the interaction between the identified compounds will be characterized in terms of selectivity and kinetics. A major advantage with the present technique is that structural knowledge for the target proteins to be used is not required. Read more >
For more information about Beactica, please visit www.beactica.com.
Introduction from the University of Cambridge (S. Lummis)
The Lummis group at the University of Cambridge has a particular interest in the 5-HT3 receptor, a protein that is the target of anti-nausea and anti-emetic drugs. The 5-HT3 receptor is a member of the pentameric Cys-loop family of neurotransmitter-gated ion channels, but is unusual in that can function with five identical subunits, thus providing a useful experimental system for understanding critical features of all Cys-loop eceptors. Read more >
Introduction from the European Molecular Biology Laboratory (C. Gross)
The Gross laboratory is responsible for the production of transgenic mice expressing genetically encoded fluorescent sensors for the readout of intracellular chloride and CLR activity. Several transgenic technologies will be used to achieve these aims, including gene targeting in mouse ES cells to alter endogenous genes (insertion of intracellular loop FRET tags to monitor CLR activity) or introduce novel genes (recombination mediated exchange [RMCE] at defined chromosomal locations) and pronuclear and intracytoplasmic sperm injection transgenesis for the random integration of promoter-reporter constructs.
Introduction from ProteoSys AG (A. Schrattenholz)
ProteoSys AG is a biotechnology SME with strong track record in European research projects (FP-5-7). We are focused on systems biology based on quantitative and differential analysis of protein biomarker signatures from functional models. This includes proprietary technology platforms, as well as state-of-the-art infrastructure with robotics, automated mass spectrometry, sequencing, liquid chromatography, etc.
Great attention is paid to the integration and synchronisation of functional (cell culture, fluorescent imaging microscopy, enzymatic tests) and molecular data (proteomic detail of posttranslational modifications of key surrogate biomarkers) In terms of bioinformatic resources, ProteoSys has developed a suite of tools and programmes, for statistical treatment of primary data, integration of a variety of data layers, data base solutions and data mining/modelling.
Introduction from Katholieke Universiteit Leuven (C. Ulens)
The Laboratory of Structural Neurobiology investigates the relationship between structure and function for different ion channels. Within Neurocypres we are involved in studying cys-loop receptor homologs from prokaryotic and eukaryotic origin. Our focus is on
1) bacterial ligand-gated ion channels
2) mammalian5HT3 receptors and
3) acetylcholine binding proteins.
We are studying these ion channel homologs using a combination of FSEC detergent screening, X-ray crystallography, two-electrode voltage clamp, site-directed mutagenesis and radiolabeled binding assays.
Introduction from the team Medical University Vienna (W. Sieghart)
Prof. Sieghart has a long standing interest in the structure and pharmacology of GABAA receptor subtypes. He was the first to demonstrate a molecular heterogeneity of GABAA receptors in the brain. He determined the stoichiometry and subunit arrangement of GABAA receptors, and provided important information on the location of allosteric binding sites (sites that do not bind the primary ligand GABA) using homology modelling. The allosteric binding sites modulate activity of the GABA receptor and well-know compounds that bind to it are substances found in todays sleeping pills. Read more >
Introduction from the team Pasteur Institute (PJ Corringer)
The groups based at the Pasteur Institute (channel-receptors headed by Prof. Corringer and structural dynamics of macromolecules headed by Marc Delarue) aim at understanding, at an atomic resolution, the function of cys-loop receptors. Corringer’s group combines structural (X-ray crystallography and other biophysical techniques) and functional (electrophysiology coupled to site-directed mutagenesis) experiments. Read more >
Introduction from the team Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry (V.I. Tsetlin)
Prof. Tsetlin’s task is to provide novel neurotoxins from snake venoms. These toxins bind to the CLRs. With the aid of computer modeling his team designs and synthesizes novel alpha-conotoxins as tools for better distinguishing various subtypes of nicotinic acetylcholine receptors or other Cys-loop receptors. Read more >
Introduction team INMED (P. Bregestovski)
The team of of Prof. Bregestovski is involved in two projects: (i) development of chloride sensors and BioSensors of Cys-loop receptors for non-invasive monitoring their activity; (ii) analysis of the structural basis of glycine receptor channels dysfunction and its up-regulation. These sensors are of interest to Neurobiological researchers. Read more >
Introduction Geneva Team (Daniel Bertrand)
Specialized in functional studies of membrane proteins the Geneva team is focusing on the neuronal nicotinic acetylcholine receptors. Using electrophysiological approaches they can measure the functional properties of proteins expressed in cell lines or Xenopus oocytes. Taking advantage of recent technical developments they were able to investigate the effects of novel toxins at nicotinic acetylcholine receptor subtypes and to characterize new ligand gated channels isolated from bacteria. The Neurocypres consortium represents an enormous advantage for the progress made in such collaborative efforts. Read more >
Introduction UNIMORE team (Michele Zoli)
The expertise of the Zoli group is the analysis of nicotinic acetylcholine receptors (nAChRs) with morphological, neurochemical and behavioural approaches. Our purpose is to study composition and functional role of nAChRs of the living brain in physiological as well pathological states (e.g., nicotine addiction, neurodegenerative diseases). Read more >