Search for European Projects

29 European Projects Found

Searched on 125080 European Projects

 FINISHED 

Tumour suppressor p53: structure, stability and novel anti-cancer drug development (P53LAZARUS)

Start date: Aug 1, 2011, End date: Jul 31, 2017,

Elimination of the tumour suppression activities of p53 is common to all cancers. p53 is inactivated directly by mutation in ~50% of human cancers, and ~30-40% of these oncogenic mutants are just temperature sensitive, ts, being active at lower temperatures. Wild-type p53 spontaneously denatures, with a half-life of 10-20 minutes at body temperature, and ts mutants far faster. The melting temperat ...
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Systematic dissection of molecular machines and neural circuits coordinating C. elegans aggregation behaviour (ACMO)

Start date: Apr 1, 2011, End date: Mar 31, 2017,

Elucidating how neural circuits coordinate behaviour, and how molecules underpin the properties of individual neurons are major goals of neuroscience. Optogenetics and neural imaging combined with the powerful genetics and well-described nervous system of C. elegans offer special opportunities to address these questions. Previously, we identified a series of sensory neurons that modulate aggregat ...
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Macromolecular machines that regulate mRNA poly(A) tails: mechanisms of polyadenylation and deadenylation (POLYAMECHANISMS)

Start date: Jan 1, 2011, End date: Dec 31, 2016,

The objective of my laboratory is to understand the mechanisms of mRNA polyadenylation and deadenylation, thereby providing fundamental insight into the regulation of eukaryotic gene expression. These objectives will be met through an integrated, multidisciplinary approach combining structural, biochemical, biophysical and yeast genetic techniques. Specifically, I propose to establish how mRNA p ...
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Intracellular antibody Immunity (IAI)

Start date: Jan 1, 2012, End date: Dec 31, 2016,

Antibodies are a critical component of immune defence but they provide purely extracellular protection – once inside a cell, a pathogen is safe. This is the view of humoral immunity that has existed for over 100 years. However, recent work in my lab has led to the discovery of a missing system of antibody-mediated immunity that takes place inside infected cells. I have identified a novel cytosolic ...
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Decoding genetic switches in T helper cell differentiation (THSWITCH)

Start date: Jan 1, 2011, End date: Dec 31, 2015,

The central question of this proposal is: how are changes in cell state regulated at the transcriptomic and epigenetic level? I will tackle this question using an integrated computational and experimental approach with the T helper cell system as my model. The Th system consists of a naïve precursor cell type, and four main differentiated cell types that have some capacity to interconvert, known a ...
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 2

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European Research Training in the Ubiquitin Proteasome System (UPStream)

Start date: Nov 1, 2011, End date: Oct 31, 2015,

The main objective of the international training network UPStream is the training of a novel generation of European scientist in a critical and complex field of modern biology: the understanding of the regulation of the UPS and its potential use for drug development. The importance of this process is illustrated by the imperious necessity to destroy certain proteins during several phases of the ce ...
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"""RNPnet"" - RNP structure, function and mechanism of action" (RNPNET)

Start date: Nov 1, 2011, End date: Oct 31, 2015,

RNA molecules are at the heart of life. It is now commonly admitted that nearly all the human genome is transcribed, and a wealth of new coding and non-coding RNAs have been discovered. Importantly, modern RNAs are never naked, but always exist in complex with proteins to form RNPs (Ribonucleoproteins). In the case of non-coding RNAs, these proteins are usually stably associated with the RNA and h ...
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 15

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MOLECULAR MECHANISM OF CAVEOLAR STRUCTURE AND FUNCTION (FUNCTION OF CAVEOLAE)

Start date: Dec 21, 2012, End date: Jul 11, 2015,

Caveolae are small invaginations of the plasma membrane, with characteristic flask-shaped morphology, found in most mammalian cells. Phenotypes of mice lacking genes for caveolins, key protein components of caveolae, show that these structures are involved in many physiological processes, such as vesicle trafficking, cholesterol homeostasis, signal transduction, tumor suppression and mechanosensin ...
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Systems Biology of Mitosis (MitoSys)

Start date: Jun 1, 2010, End date: May 31, 2015,

"MitoSys will generate a comprehensive mathematical understanding of mitotic division in human cells, a process of fundamental importance for human health. To create the critical mass and multidisciplinarity that is needed to achieve this ambitious goal, internationally leading mathematicians, biochemists/biophysicists and biologists working at twelve universities, research institutes, internation ...
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 14

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Encoded Cellular Synthesis of Unnatural Biopolymers (ECSUB)

Start date: Jan 1, 2009, End date: Dec 31, 2014,

We are building a parallel and independent (orthogonal) translational machinery for the encoded biosynthesis of unnatural polymers in living cells. The orthogonal translation system has many potential applications beyond those possible with the natural translation system: I propose to use it: 1) To expand the chemical scope of monomers that can be polymerized by the ribosome in living cells, allow ...
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Intracellular protein aggregation: fitness and evolution (Fitness & Evolution)

Start date: Sep 1, 2012, End date: Aug 31, 2014,

Protein misfolding and aggregation are associated with an increasing number of human disorders, such as Alzheimer’s disease and Parkinson’s disease. Additionally, the formation of insoluble deposits during recombinant protein production impedes the commercialization of several peptide drugs. Recent computational studies highlight the existence of a selective pressure to escape from protein aggrega ...
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Neural Basis of Olfactory Perception in Drosophila (OlfPercept)

Start date: Sep 1, 2008, End date: Aug 31, 2014,

In insects the axons of primary olfactory receptor neurons terminate in specific glomeruli in the antennal lobe. Second order neurons relay this information to two higher olfactory centres, the mushroom body and the lateral horn, the special focus of this proposal. Functional inactivation and ablation of the mushroom body suggest that it is specific to olfactory learning, while the lateral horn is ...
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Structure and Function of the Dynein Tail (DYNTAIL)

Start date: Jul 1, 2012, End date: Jun 30, 2014,

"Movement is a defining characteristic of life at the sub-cellular level. Dynein is one of the motor proteins that power this movement. It carries a wide range of cargos and dynein dysfunction has been implicated in many human diseases. Unlike other motors only one cytoplasmic dynein exists which suggests that it has unique mechanisms for controlling specificity i.e. how it carries cargo to the ri ...
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Molecular mechanims of mRNA transport in neurons (neuroRNAtransport)

Start date: Jul 1, 2012, End date: Jun 30, 2014,

RNA transport coupled to local translation presents an efficient means to regulate gene expression in time and space. Recent studies have indicated that this mode of post-transcriptional regulation is used in many different cell types and applied to hundreds to thousands of transcripts. mRNA transport is of particular importance in neurons, where it is involved in processes such as axon guidance a ...
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The molecular regulation of T helper cell subtype plasticity (ThPLAST)

Start date: Aug 8, 2011, End date: Feb 4, 2014,

Naïve CD4+ T cell differentiate into distinct lineages to achieve successful adaptive immune responses to diverse categories of pathogens. The development of these effector cells is controlled by cytokines, transcription factor interactions and chromatin modifications. In addition, several of the differentiated subtypes can interconvert, a property known as plasticity. However, the molecular regu ...
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How is phosphoinositide 3-kinase beta regulated by G-Protein Coupled Receptors and by Rab-5? (beta)

Start date: Jan 1, 2012, End date: Dec 31, 2013,

Many signaling pathways in human cells involve lipid recognition events. The phosphorylation state of these lipids is under the control of both lipid kinases and lipid phosphatases. The phosphorylated second messenger lipids recruit lipid adaptor molecules, which regulate fundamental cellular processes including cell survival, proliferation, motility, differentiation and intracellular trafficking. ...
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How protein complexes recognize and modify chromatin: Structural studies on MSL1-MSL3-MOF Dosage Compensation Complex bound to nucleosomes (MSL1-MSL3-MOF)

Start date: Oct 1, 2011, End date: Sep 30, 2013,

"Metazoa evolved homogametic and heterogametic sexes. In heterogametic sexes one of the two sex chromosomes underwent loss of essential genes and molecular mechanisms evolved to compensate for this loss.In fruit flies, males up-regulate the transcription levels of many genes on the only sex chromosome by 2-fold. This effect is associated with acetylation of H4K16 mediated by MOF, the catalytic sub ...
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Mapping functional protein-RNA interactions to identify new targets for oligonucleotide-based therapy (CLIP)

Start date: Sep 1, 2008, End date: Aug 31, 2013,

An important question of modern neurobiology is how neurons regulate synaptic function in response to excitation. In particular, the roles of alternative pre-mRNA splicing and mRNA translation regulation in this response are poorly understood. We will study the RNA-binding proteins (RBPs) that control these post-transcriptional changes using a UV crosslinking-based purification method (CLIP) and u ...
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Fast and slow endocytosis at the synapse (FSES)

Start date: Jun 1, 2011, End date: May 31, 2013,

"The mechanism of neurotransmitter release is a fundamental aspect of nervous system function, but it is still highly controversial. There is overwhelming evidence that vesicles can release their contents by fully collapsing into the cell surface, after which they are retrieved slowly (10-20 s) by formation of a clathrin cage around the membrane. But it has also been suggested that there is a seco ...
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Structural and Biochemical Examination of the Yeast U4/U6 snRNP (StructureU4U6snRNP)

Start date: Apr 1, 2011, End date: Mar 31, 2013,

The spliceosome is a large RNA–protein assembly that catalyzes the removal of introns from mRNA precursors (pre-mRNA) and the splicing of coding exons to produce mature mRNAs. Four small nuclear ribonucleoprotein particles (U1, U2, U5 and U4/U6 snRNPs) assemble onto pre-mRNA substrates together with non-snRNP proteins to form the spliceosome. After binding of the U1 snRNP and the U2 snRNP to the ...
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Biochemical and Structural characterization of signal transduction by OTU family of Deubiquitinases (BISSOT'D)

Start date: Apr 1, 2010, End date: Mar 31, 2012,

"Ubiquitination is a reversible post-translational modification (PTM) regulating diverse cellular functions including cell cycle, apoptosis, gene expression, inflammation and DNA repair. Ubiquitination results in the tagging of proteins with either monoubiquitin or polyubiquitin chains of different linkages that are structurally distinct. Given that protein ubiquitination is involved in so many ce ...
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 1

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GSK-3 in neuronal plasticity and neurodegeneration: basic mechanisms and pre-clinical assessment (NEURO.GSK3)

Start date: Oct 1, 2008, End date: Dec 31, 2011,

"Neuronal circuits in mammalian brain act predominantly via excitatory synapses on dendritic spines. Formation of new spines in adult brain constitutes the structural basis of neuronal plasticity. The underlying molecular mechanisms remain largely unknown but depend essentially on kinase-dependent signalling pathways. Final formation of synapses on spines depends on dynamic interactions of microtu ...
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Structural studies on the ParMRC plasmid DNA partitioning complex (ParMRC)

Start date: Apr 1, 2009, End date: Mar 31, 2011,

The segregation of newly replicated DNA is an essential process in all prokaryotes and eukaryotes, ensuring the propagation of DNA to daughter cells. In bacteria, the plasmid partitioning system helps in the proper segregation of low copy number plasmids during cell division. The type II plasmid partitioning system (ParMRC) consists of three major elements – a parC DNA site, which acts as a centro ...
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Information processing in distal dendrites of neocortical layer 5 pyramidal neurons (Channelrhodopsin)

Start date: Mar 1, 2009, End date: Feb 28, 2011,

The aim of the current proposal is to investigate how synaptic inputs that innervate the distal dendrites of central neurons are integrated to form a neuronal output. The distal dendritic tree is the dendritic compartment furthest away from the action potential initiation zone. In the neocortex ascending afferent and intra-cortical information converges in neocortical layer 1 suggesting a prominen ...
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Microcrystallography of stabilized adrenergic receptors (BAR structure)

Start date: Jan 1, 2009, End date: Dec 31, 2010,

Nowadays microfocus beamlines at intense and brilliant synchrotron radiation sources allow studies of samples with low X-ray scattering power to be curried out with new micro-methods. Structural information of excellent quality can be produced for proteins, which crystallize yielding only tiny crystals. The structure of recombinant rhodopsin obtained recently in host laboratory is an example of su ...
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Control of cell shape in the peripodial membrane of the wing disc of Drosophila melanogaster (cell shape, fly)

Start date: Jun 1, 2008, End date: Dec 31, 2010,

I propose to analyze how epithelial cell shape is controlled, using the Drosophila peripodial membrane as a model system. Drosophila third instar imaginal discs are a composed of two contiguous layers of cells of distinct morphology: a pseudostratified one, called the proper epithelium (PE), and a squamous epithelium, the peripodial membrane (PM). While the PE has been deeply studied, little is kn ...
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Structural characterization of a mammalian mitochondrial ribosome and its complexes by the X-ray crystallography (MITOCHONDR RIBOSOME)

Start date: Jul 1, 2010, End date: Dec 31, 2010,

"The ribosome is a large ribonucleoprotein particle which translates mRNA to proteins through a sophisticated process that combines high speed and accuracy. It thus plays a central role in protein biosynthesis, translation, which is a fundamental and essential process in all cells. Mitochondria contain a translational system that is distinct from that of the cell cytoplasm. Mitochondrial ribosomes ...
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Dissecting dynamic monoaminergic nervous system in C. elegans with genetically-encoded neuron activator protein channelrhodopsin-2 (YTANIZAWA)

Start date: Jun 1, 2008, End date: May 31, 2010,

"Biogenic monoamines are relevant to influential psychological diseases and brain plasicity. Knowledge obtained so far is however not enough for both of scientific and medical purposes. One obstacle against proceeding is the difficulty to find novel genes in genetically-inaccessible system like human brain. Another problem is the complexity of brain making it difficult to link cellular phenomena t ...
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Structural and biophysical mechanism of microRNA nuclear export (MicroRNA Export)

Start date: May 12, 2008, End date: May 11, 2010,

MicroRNAs are a recently discovered class of small non-coding RNAs that act as post-transcriptional regulators of gene expression by silencing target mRNAs. They have wide ranging roles in many cellular processes including cellular proliferation, stress response, apoptosis, development and differentiation. Altered expression of microRNA has been implicated in tumorigenesis, and microRNAs are recog ...
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