Marc Blondel

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• Professor of Cell Biology
• Professor (Full) at Université de Bretagne Occidentale

We have developed a rapid, yeast-based, two-step assay to screen for antiprion drugs. The method allowed us to identify several compounds effective against budding yeast prions responsible for the [PSI+] and [URE3] phenotypes. These inhibitors include the kastellpaolitines, a new class of compounds, and two previously known molecules, phenanthridin...

The oncogenic Epstein-Barr virus (EBV) evades the immune system but has an Achilles heel: its genome maintenance protein EBNA1, which is essential for viral genome maintenance but highly antigenic. EBV has seemingly evolved a system in which the mRNA sequence encoding the glycine-alanine repeats (GAr) of the EBNA1 protein limits its expression to t...

The oncogenic Epstein-Barr virus (EBV) evades the immune system through limiting the expression of its highly antigenic and essential genome maintenance protein, EBNA1, to the minimal level to ensure viral genome replication, thereby also minimizing the production of EBNA1-derived antigenic peptides. This regulation is based on inhibition of transl...

The oncogenic Epstein-Barr virus (EBV) evades the immune system but has an Achilles heel: its genome maintenance protein EBNA1. Indeed, EBNA1 is essential for viral genome maintenance but is also highly antigenic. Hence, EBV seemingly evolved a system in which the glycine–alanine repeat (GAr) of EBNA1 limits the translation of its own mRNA to the m...

BCL-x is a master regulator of apoptosis whose pre-mRNA is alternatively spliced into either a long (canonical) anti-apoptotic Bcl-xL isoform, or a short (alternative) pro-apoptotic Bcl-xS isoform. The balance between these two antagonistic isoforms is tightly regulated and overexpression of Bcl-xL has been linked to resistance to chemotherapy in s...

Mastitis is a major issue for the dairy industry. Despite multiple attempts, the efficacy of available mastitis vaccines is limited and this has been attributed to their incapacity to trigger robust cell-mediated immunity. Yeasts have recently been identified as promising antigen vectors capable of inducing T-cell responses, surpassing the antibody...

Seed dormancy corresponds to a reversible blockage of germination. Primary dormancy is established during seed maturation, while secondary dormancy is set up on the dispersed seed, following an exposure to unfavorable factors. Both dormancies are relieved in response to environmental factors, such as light, nitrate, and coldness. Quantitive Trait L...

Background Microsatellite instability (MSI) due to mismatch repair deficiency (dMMR) is common in colorectal cancer (CRC). These cancers are associated with somatic coding events, but the noncoding pathophysiological impact of this genomic instability is yet poorly understood. Here, we perform an analysis of coding and noncoding MSI events at the d...

Seed dormancy corresponds to a reversible blockage of germination. Primary dormancy is established during seed maturation while secondary dormancy is set up on the dispersed seed, following an exposure to unfavourable factors. Both dormancies are relieved in response to environmental factors, such as light, nitrate and coldness. QTL analyses for pr...

The Epstein-Barr virus (EBV) is the first oncogenic virus described in human. EBV infects more than 90% of the human population worldwide, but most EBV infections are asymptomatic. After the primary infection, the virus persists lifelong in the memory B cells of the infected individuals. Under certain conditions the virus can cause several human ca...

Protein aggregates and abnormal proteins are toxic and associated with neurodegenerative diseases. There are several mechanisms to help cells get rid of aggregates but little is known on how cells prevent aggregate-prone proteins from being synthesised. The EBNA1 of the Epstein-Barr virus (EBV) evades the immune system by suppressing its own mRNA t...

Mitochondrial complex V plays an important role in oxidative phosphorylation by catalyzing the generation of ATP. Most complex V subunits are nuclear encoded and not yet associated with recognized Mendelian disorders. Using exome sequencing, we identified a rare homozygous splice variant (c.87+3A>G) in ATP5PO, the complex V subunit which encodes th...

The role of G-quadruplex (G4) RNA structures is multifaceted and controversial. Here, we have used as a model the EBV-encoded EBNA1 and the Kaposi’s sarcoma-associated herpesvirus (KSHV)-encoded LANA1 mRNAs. We have compared the G4s in these two messages in terms of nucleolin binding, nuclear mRNA retention, and mRNA translation inhibition and thei...

Prion diseases are caused by the propagation of PrPSc, the pathological conformation of the PrPC prion protein. The molecular mechanisms underlying PrPSc propagation are still unsolved and no therapeutic solution is currently available. We thus sought to identify new anti-prion molecules and found that flunarizine inhibited PrPSc propagation in cel...

Background Hydrogen sulfide (H2S) is an endogenous mammalian gasotransmitter. Cystathionine β-synthase (CBS), cystathionine γ -lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3-MST) are the principal enzymes responsible for its biogenesis. A recent yeast screen suggested that disulfiram (a well-known inhibitor of aldehyde dehydrogenase and a...

The Epstein–Barr (EBV) virus is linked to at least 1% of human cancers that include Burkitt's and Hodgkin's lymphomas, nasopharyngeal carcinoma, and 10% of gastric cancers. EBV is a latent virus that possesses a genome maintenance protein, EBNA1, which is both essential for the virus and highly antigenic. Hence, EBV has evolved a mechanism by which...

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inheritable cause of end stage renal disease and, as of today, only a single moderately effective treatment is available for patients. Even though ADPKD research has made huge progress over the last decades, the precise disease mechanisms remain elusive. However, a wide variety...

La levure a été utilisée de façon empirique pendant des millénaires pour la panification et la fermentation des sucres en alcool. C’est seulement à partir de 1857 que Louis Pasteur décrit le microorganisme à l’origine de ces deux activités agroalimentaires majeures. Dès lors, les souches de levure ont pu être sélectionnées et modifiées sur une base...

The current SARS‐CoV‐2 pandemic is wreaking havoc throughout the world and has rapidly become a global health emergency. A central question concerning COVID‐19 is why some individuals become sick and others not. Many have pointed already at variation in risk factors between individuals. However, the variable outcome of SARS‐CoV‐2 infections may, at...

Fipronil is an insecticide widely used for veterinary and agricultural purposes. While its insecticidal properties mostly rely on its high affinity antagonistic activity on insect γ aminobutyric acid (GABA) receptors, fipronil and its main metabolite fipronil sulfone nevertheless display non-negligible affinity for mammalian GABAA receptor. As seve...

Many pathogens (virus, bacteria, fungi, or parasites) have developed a wide variety of mechanisms to evade their host immune system. The budding yeast Saccharomyces cerevisiae has successfully been used to decipher some of these immune evasion strategies. This includes the cis-acting mechanism that limits the expression of the oncogenic Epstein–Bar...

Fig. S1. Effect of hexestrol and clomifene on mitochondrial morphology and mtDNA in galactose medium Yeast cells expressing the mitochondrial protein Arg11p fused to the fluorescent mCherry protein (Arg11p-mCherry), together with mutated Msp1p (strain msp1 P300S) were cultured at 37°C in galactose medium for 18 hours without (-) or with 20 µM hexes...

Mitochondria continually move, fuse and divide, and these dynamics are essential for the proper function of the organelles. Indeed, the dynamic balance of fusion and fission of mitochondria determines their morphology and allows their immediate adaptation to energetic needs as well as preserving their integrity. As a consequence, mitochondrial fusi...

Identifying dosage-sensitive genes is a key to understand the mechanisms underlying intellectual disability in Down syndrome (DS). The Dp(17Abcg1-Cbs)1Yah DS mouse model (Dp1Yah) shows cognitive phenotypes that need to be investigated to identify the main genetic driver. Here, we report that three copies of the cystathionine-beta-synthase gene (Cbs...

Peptides presented on major histocompatibility (MHC) class I molecules form an essential part of the immune system’s capacity to detect virus-infected or transformed cells. Earlier works have shown that pioneer translation peptides (PTPs) for the MHC class I pathway are as efficiently produced from introns as from exons, or from mRNAs targeted for...

Protein-RNA interactions (PRIs) control pivotal steps in RNA biogenesis, regulate multiple physiological and pathological cellular networks, and are emerging as important drug targets. However, targeting of specific protein-RNA interactions for therapeutic developments is still poorly advanced. Studies and manipulation of these interactions are tec...

Identifying dosage sensitive genes is a key to understand the mechanisms underlying intellectual disability in Down syndrome (DS). The Dp(17Abcg1-Cbs)1Yah DS mouse model (Dp1Yah) show cognitive phenotype and needs to be investigated to identify the main genetic driver. Here, we report that, in the Dp1Yah mice, 3 copies of the Cystathionine-beta-syn...

The presence of the Epstein-Barr virus (EBV)-encoded nuclear antigen-1 (EBNA1) protein in all EBV-carrying tumours constitutes a marker that distinguishes the virus-associated cancer cells from normal cells and thereby offers opportunities for targeted therapeutic intervention. EBNA1 is essential for viral genome maintenance and also for controllin...

Elucidating the biology of yeast in its full complexity has major implications for science, medicine and industry. One of the most critical processes determining yeast life and physiology is cellular demise. However, the investigation of yeast cell death is a relatively young field, and a widely accepted set of concepts and terms is still missing....

Elucidating the biology of yeast in its full complexity has major implications for science, medicine and industry. One of the most critical processes determining yeast life and physiology is cellular demise. However, the investigation of yeast cell death is a relatively young field, and a widely accepted set of concepts and terms is still missing....

The oncogenic Epstein-Barr virus (EBV) evades the immune system but has an Achilles heel: its genome maintenance protein EBNA1. Indeed, EBNA1 is essential for viral genome replication and maintenance but also highly antigenic. Hence, EBV evolved a system in which the glycine-alanine repeat (GAr) of EBNA1 limits the translation of its own mRNA at a...

Bcs1p is a chaperone that is required for the incorporation of the Rieske subunit within complex III of the mitochondrial respiratory chain. Mutations in the human gene BCS1L (BCS1-like) are the most frequent nuclear mutations resulting in complex III-related pathologies. In yeast, the mimicking of some pathogenic mutations causes a respiratory def...

Supplementary data Lista et al Nature Communications 2017

Since its discovery in 1979, p53 has been on the forefront of cancer research. It is considered a master gene of cancer suppression and is found mutated in around 50% of all human tumors. In addition, the progressive identification of p53-related transcription factors p63 and p73 as well as their multiple isoforms have added further layers of compl...

Cove page: The cover shows the in the one-pot conversion of free fatty acids and triglycerides, a lipase producing recombinant Aspergillus oryzae immobilized on matrix (sponge like matrix) can directly convert to bio-diesel from mixture of substrate. The cover is prepared by Jerome Amoah, Emmanuel Quayson, Shinji Hama, Ayumi Yoshida, Tomohisa Hasun...

Editorial Office Deputy Editors: Jing Zhu and Uta Göbel Editorial Office:

It is no longer necessary to demonstrate that ribosome is the central machinery of protein synthesis. But it is less known that it is also key player of the protein folding process through another conserved function: the protein folding activity of the ribosome (PFAR). This ribozyme activity, discovered more than two decades ago, depends upon the d...

6AP and GA are potent inhibitors of yeast and mammalian prions and also specific inhibitors of PFAR, the protein-folding activity borne by domain V of the large rRNA of the large subunit of the ribosome. We therefore explored the link between PFAR and yeast prion [PSI⁺] using both PFAR-enriched mutants and site-directed methylation. We demonstrate...

The tumor suppression activity of p53 is frequently impaired in cancers even when a wild-type copy of the gene is still present, suggesting that a dominant-negative effect is exerted by some of p53 mutants and isoforms. p63 and p73, which are related to p53, have also been reported to be subjected to a similar loss of function, suggesting that a do...

6AP and GA are potent inhibitors of yeast and mammalian prions and also specific inhibitors of PFAR, the protein-folding activity borne by domain V of the large rRNA of the large subunit of the ribosome. We therefore explored the link between PFAR and yeast prion [PSI+] using both PFAR-enriched mutants and site-directed methylation. We demonstrate...

The Epstein-Barr gammaherpesvirus (EBV) is the first oncogenic virus discovered in human. Indeed, EBV has been known for more than 50 years to be tightly associated with certain human cancers. As such, EBV has been the subject of extensive studies aiming at deciphering various aspects of its biological cycle, ranging from the regulation of its geno...

Mitochondrial diseases are severe and largely untreatable. Owing to the many essential processes carried out by mitochondria and the complex cellular systems that support these processes, these diseases are diverse, pleiotropic, and challenging to study. Much of our current understanding of mitochondrial function and dysfunction comes from studies...

Mitochondrial diseases are systemic, prevalent and often fatal; yet treatments remain scarce. Identifying molecular intervention points that can be therapeutically targeted remains a major challenge, which we confronted via a screening assay we developed. Using yeast models of mitochondrial ATP synthase disorders, we screened a drug repurposing lib...

Since its discovery and description by Louis Pasteur, the budding yeast Saccharomyces cerevisiae, which was used for thousands of years for alcoholic fermentation and as a leavening agent, has become a popular model system in biology. One of the reasons for this popularity is the strong conservation from yeast to human of most of the pathways contr...

The EBV-encoded EBNA1 was first discovered 40 years ago, approximately 10 years after the presence of EBV had been demonstrated in Burkitt's lymphoma cells. It took another 10 years before the functions of EBNA1 in maintaining the viral genome were revealed and it has since been shown to be an essential viral factor expressed in all EBV-carrying ce...

Series of 6-aminophenanthridines and related heterocyclic compounds such as benzonaphtyridines were prepared. Reduction of one of the three aromatic rings was also performed. The compounds were first tested for their antiprion activity in a previously described yeast-based colourimetric prion assay. The most potent derivatives were then assayed ex...

Cross-complementation studies offer the possibility to overcome limitations imposed by the inherent complexity of multicellular organisms in the study of human diseases, by taking advantage of simpler model organisms like the budding yeast Saccharomyces cerevisiae. This review deals with, (1) the use of S. cerevisiae as a model organism to study hu...

Epstein-Barr virus (EBV) is tightly associated to certain human cancers but there is of today no specific treatment against EBV-related diseases. The EBV-encoded EBNA1 protein is essential to maintain viral episomes and for viral persistence. EBNA1 is expressed in all EBV infected cells and is highly antigenic. All infected individuals, including c...

This special issue of Biotechnology Journal on fluorescent biosensors is edited by Dr. May Morris and Prof. Marc Blondel.

Using a yeast-based assay, a previously unsuspected antiprion activity was found for imiquimod (IQ), a potent Toll-like receptor 7 (TLR7) agonist already used for clinical applications. The antiprion activity of IQ was first detected against yeast prions [PSI (+) ] and [URE3], and then against mammalian prion both ex vivo in a cell-based assay and...

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Cells from red halos surrounding filters on which IQ (A) or IQ, 4b, 4c, 4d, 8a, 8b (B) was loaded were streaked on drug-free YPD medium. Cells surrounding filters on which DMSO and GuHCl were loaded were used as negative and positive controls, respectively. (TIF)

Domain V of the 23S/25S/28S rRNA of the large ribosomal subunit constitutes the active center for the protein folding activity of the ribosome (PFAR). Using in vitro transcribed domain V rRNAs from Escherichia coli and Saccharomyces cerevisiae as the folding modulators and human carbonic anhydrase as a model protein, we demonstrate that PFAR is con...

An original yeast-based phenomic model for DeltaF508 CFTR, by far the most prevalent allele of the CFTR gene responsible for cystic fibrosis, has been developed by the groups of Elizabeth A Miller and John L Hartman. This model allows potential modifier genes of the DeltaF508 CFTR allele to be uncovered. Hence, brewer's yeast Saccharomyces cerevisi...

Due to the lack of relevant animal models, development of effective treatments for human mitochondrial diseases has been limited. Here we establish a rapid, yeast-based assay to screen for drugs active against human inherited mitochondrial diseases affecting ATP synthase, in particular NARP (neuropathy, ataxia, and retinitis pigmentosa) syndrome. T...