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Bacillus subtilis mRNA metabolism and gene expression : a study on the function and structure of the novel and essential ribonucleases Y and J – RNAJAY
Proteins are synthesized from amino acids using messenger RNA (mRNA) molecules as a matrice in a process called «translation«. These mRNAs represent copies of the genes that code for these proteins. However, in contrast to DNA which is very stable, mRNA is a very fragile molecule which generally has
Cap-driven Internal Translation Initiation – MITIC
We have recently shown that histone H4 translation is initiated by an new mechanism that recapitulates some cellular (cap-dependence) and viral features (absence of scanning and internal ribosomal entry site). In opposition to classical mRNAs, the 5’-cap of histone H4 mRNA is not free but tightly pa
Structure/function study of the respiratory syncytial virus polymerase and search for inhibitors – BRONCHIOLITEASER
The respiratory syncytial virus (RSV) is the main cause of bronchiolitis and pneumonia in young children and newborn calves. There is no vaccine for humans nor antiviral drugs available. The aim of this project is to better characterize the RNA-dependant RNA polymerase complex (RdRp) of RSV at the s
Structure-function relationships of retinoic acid receptors from genome-wide to atomic scales. – RAR-SCALES
The objective of this proposal is to profile RAR-and RXR genomic occupancy during differentiation, identify and characterise non-canonical binding elements and determine if and how the primary sequence and topological organisation of the RAR binding sites may act as allosteric regulators of the RAR/
Structure-properties relationship within highmolecular weight protein oligomeric species associated to Parkinson’s and Huntigton diseases – STRUCTOXIC
The neurodegenerative diseases of Alzheimer, Parkinson, Huntington etc… have high societal costs for our ageing societies. We aim to characterize the structural properties of alpha-synuclein assemblies at the origin of Parkinson’s disease After sequential assignments of an alpha-synuclein polymorph,
Integrative study of Mediator function in transcription regulation. – IntegraMed
Transcription regulation constitutes a key mechanism in the regulation of gene expression and, hence, in the regulation of gene expression and in the functioning of live cells. This process is highly regulated to ensure that cells mounts appropriate responses to their external or tissular environme
Structural and functional exploration of a novel family of proteins having RNase P activity – PRO-RNase P
The discovery and characterisation of this novel kind of proteinaceous RNase P is very recent. Thus, the proposed research aims at getting a much deeper insight into the functions and mode of action of the new proteinaceous RNase P. This research will be multidisciplinary. Through complementary appr
Mechanism of protein biosynthesis in prokaryotes and eukaryotes studied by X-ray analysis – SSOTR
Our study will increase the knowledge about the main cellular factories responsible for making proteins (ribosome). Subsequently this will bring us closer to the ultimate goal- understanding of human ribosomes, its structure and biochemical details of protein synthesis in human cell. There are many
Molecular assembly of the pneumococcal pilus . From a natural to a biotechnological toolbox – PILIPATH
Streptococcus pneumoniae causes most cases of pneumonia, otitis, sinusitis, sepsis and meningitis in humans leading to about 1.6 million people yearly. Combating pneumococcal diseases is hampered by the replacement of vaccine serotypes within populations and the dissemination of antibiotic resistant
Structural determinants of lactococcal Siphoviridae phages infectivity – Lacto-Phages
Phages with tails (Caudovirales) belong to three families, among which Siphoviridae possess a non contractile tail terminated by a tail tip or a baseplate serving for phage adsorption on its host. While the mechanism of bacterial infection by the two other Caudovirales families has been well documen
The Orange Carotenoid Protein : a photoactive protein involved in photoprotection in cyanobacteria – CYANOPROTECT
The ambition of CYANOPROTECT is to create a multidisciplinary network of field-leading, highly -productive laboratories able to unravel the basic molecular mechanism of photoprotection in cyanobacteria, elucidate the photocycle of a new photoactive protein and further understand the role of proteins
Rhabdovirus fusion machinery – MAFUR
The goal of this project is to obtain a detailed understanding at a molecular level of membrane fusion mechanisms using the rhabdovirus glycoprotein as a model system. We have already characterized two structures of the glycoprotein of vesicular stomatitis virus (the so-called post-and pre-fusion fo
Propagation of an amyloid fold as a mean of signal transmission between a STAND protein and a prion – STANDPRION
The aim of the project, is to establish and describe, a functional interplay between STAND proteins and their effector domains. The activation of the effector domain is ensured by transmission of an amyloid fold from the STAND protein to the effector domain by propagation of an amyloid fold. In this
Impacts of RNA polymerase II transcription on EJC assembly – EJCbirth
The EJC is assembled onto mRNA by splicing. It is essential for mRNA lifecycle; mRNA transport, translation and stability can be affected by EJC. We recently showed that EJC is not constitutively deposited suggesting that it assembly is regulated. When transcription is affected, pre-mRNA splicing c
Tolerance of DNA lesions – ForkRepair
Le génome de tout organisme vivant est continuellement endommagé par des agents endogènes (mécanismes oxydatifs,…) ou par des agents exogènes chimiques (fumée de cigarette,….) ou physique (rayonnement solaire). Les mutations sont des changements irréversibles du message génétique qui s’induisent lor
Centriole and cilia: organization and dynamics – CCOD
Centrioles (in the centrosome) and basal bodies (in cilia and flagella) are alike and play essential roles in cell division and cell motility. Deregulation of the duplication of centrioles is linked to tumor generation. Similarly, structural and functional modifications of cilia and flagella can lea
The Hsp90-R2TP machinery and the assembly of macromolecular complexes: role in RNP biogenesis. – Hsp90assembly.com
The Hsp90 molecular chaperone and its R2TP cochaperone form an assembly and maturation system for complex molecular machines that are essential to cell life. To shed light on the mode of action of the Hsp90-R2TP system, we will analyze its architecture and the interactions it forms during the assem
Molecular basis of post-meiotic male genome reprogramming – EpiSperm2
In mammals, post-meiotic male genome reorganization and compaction could be considered as conceptually related to sporulation in lower eukaryotes or pollen formation in plants, since all consist in preparing the genome to confront the hostile exterior environment. All involve post-meiotic genome com
Regulation of alternative splicing by the RNAi machinery – iSPLICE
In the cytoplasm, Argonaute (AGO) proteins in the context of the RISC complex use small RNAs to target mRNAs for degradation or inhibit their translation. In the nucleus, we find these proteins associated with splicing factors. Our preliminary data indicates that AGO proteins affect alternative spli
Control of cell proliferation and genetic stability by the Tip60 and p400 enzymes – PinGS
The objective of this project is to study the role of p400 and Tip60 in cell proliferation and in the maintenance of genetic information, two processes which are defective in human cancers. We will also investigate the role of these two proteins in cancer formation. We showed that the changes in p40
Ubiquitination and de-ubiquitination events in the regulation of viral replication – Ubi-or-not-Ubi
. . . . Cells are tightly regulated by sophisticated processes. Among them, post-translational modifications of proteins is essential. Recently, the covalent modification of proteins by ubiquitin and degradation by the proteasome has emerged as a major, critical process by which virtually all aspect
Structure, dynamics and mechanism of Arpin, a novel inhibitor of the Arp2/3 complex that controls cell migration – Dynarpin
Une cellule en migration est propulsée par la polymérisation, à l’intérieur de la cellule, d’un réseau de protéines, composé d’actine. Il s’agit d’un processus extrêmement complexe et hautement régulé. Nous avons entrepris d’en décortiquer un aspect encore mal connu, qui est le phénomène de dépolymé
Eukaryotic mRNA decapping mechanism – Decapping
Mature translatable eukaryotic mRNAs are protected from fast and uncontrolled degradation in the cytoplasm by two cis-acting stability determinants: a methylguanosine cap and a poly(A) tail at the 5’ and 3’ extremities, respectively. As a consequence, mRNA degradation necessitates a subsequent remod
Structural, mechanistic and inhibitor design studies of the Bunya- and Arenavirus L-proteins – ArenaBunya-L
The overall goal of this project is to derive a structure-based, mechanistic model to explain how segmented, negative-strand RNA viral polymerases function in both transcription and replication. Preliminary results on domain identification and expression, purification and EM of full-length bunyaviru
Structural biology of chromatin assembly and modification – Epistruct
This project addresses a long-term research effort to understand signal integration on promoters and how these signals lead to chromatin modification, remodeling and ultimately gene activation. The switching mechanisms that ultimately lead to gene activation represent relatively complex logical circ
Telomeres and dicentric chromosomes – TELO&DICENs