A5001454024- Genetics, Aging, and Longevity in Model Organisms
- CRISPR and Genetic Engineering
- Epigenetics and DNA Methylation
- Reproductive Biology and Fertility
- Cell Adhesion Molecules Research
- Genetic Mapping and Diversity in Plants and Animals
- Protein Degradation and Inhibitors
- Circadian rhythm and melatonin
- Mitochondrial Function and Pathology
- Histone Deacetylase Inhibitors Research
- Genomics and Chromatin Dynamics
- Evolution and Genetic Dynamics
- Coenzyme Q10 studies and effects
- Pancreatic function and diabetes
- Cellular transport and secretion
- Congenital heart defects research
- Ocular Oncology and Treatments
- Nonmelanoma Skin Cancer Studies
- Fungal and yeast genetics research
- Retinoids in leukemia and cellular processes
- Cancer Cells and Metastasis
- Biological Research and Disease Studies
- Ear and Head Tumors
- RNA regulation and disease
- Alzheimer's disease research and treatments
University of Manchester
2011-2024
Manchester Academic Health Science Centre
2019-2023
Université de technologie de belfort-montbéliard
2008
The Gurdon Institute
2003-2005
University of Cambridge
2003-2005
Wellcome Trust
2003-2005
Montreal Clinical Research Institute
1997-2004
Centre National de la Recherche Scientifique
1985
AbstractNeuroD1/β2 is a basic helix-loop-helix (bHLH) factor expressed in the endocrine cells of pancreas and subset neurons as they undergo terminal differentiation. We now show that NeuroD1 corticotroph pituitary gland it involved cell-specific transcription proopiomelanocortin (POMC) gene. It was previously shown corticotroph-specific POMC depends part on action cell-restricted bHLH factors were characterized CUTE (corticotroph upstream element) (M. Therrien J. Drouin, Mol. Cell. Biol....
Trimethylation of histone H3 on Lys 27 (H3K27me3) is key for cell fate regulation. The H3K27me3 demethylase UTX functions in development and tumor suppression with undefined mechanisms. Here, genome-wide chromatin occupancy analysis associated modifications reveals distinct classes target genes, including genes encoding Retinoblastoma (RB)-binding proteins. removes maintains expression several RB-binding proteins, enabling cycle arrest. Genetic interactions mammalian cells Caenorhabditis...
Stress granules are cytoplasmic mRNA-protein complexes that form upon the inhibition of translation initiation and promote cell survival in response to environmental insults. However, they often associated with pathologies, including neurodegeneration cancer, changes their dynamics implicated ageing. Here we show mTOR effector kinases S6 kinase 1 (S6K1) 2 (S6K2) localise stress human cells required for assembly maintenance after mild oxidative stress. The roles S6K1 S6K2 distinct, having a...
Homeoproteins and basic helix-loop-helix (bHLH) transcription factors are known for their critical role in development cellular differentiation. The pituitary pro-opiomelanocortin (POMC) gene is a target of both families. Indeed, pituitary-specific POMC depends on the action homeodomain-containing factor Pitx1 bHLH heterodimers containing NeuroD1. We now show lineage-restricted expression NeuroD1 corticotroph cells direct physical interaction between that results transcriptional synergism....
NeuroD1(BETA2) and Tpit are cell-specific activators of pituitary proopiomelanocortin (POMC) gene transcription. Expression both factors slightly precedes that POMC at embryonic d 12.5 mouse development. We now report is required for early corticotroph differentiation. In agreement with the transcriptional synergism observed between basic helix-loop-helix dimers containing NeuroD1(BETA2), expression delayed in NeuroD1-deficient mice. However, this differentiation defect does not reflect a...
Abstract Background RNAi technology by feeding of E. coli containing dsRNA in C. elegans has significantly contributed to further our understanding many different fields, including genetics, molecular biology, developmental biology and functional genomics. Most this research been carried out a single genotype or genetic background. However, effects one do not reveal the allelic that segregate natural populations contribute phenotypic variation. Results Here we present method allows for...
Here, we present WormQTL (http://www.wormqtl.org), an easily accessible database enabling search, comparative analysis and meta-analysis of all data on variation in Caenorhabditis spp. Over the past decade, elegans has become instrumental for molecular quantitative genetics systems biology natural variation. These efforts have resulted a valuable amount phenotypic, high-throughput genotypic across different developmental worm stages environments hundreds C. strains. provides workbench tools...
Complex traits, including common disease-related are affected by many different genes that function in multiple pathways and networks. The apoptosis, MAPK, Notch, Wnt signalling play important roles development disease progression. At the moment we have a poor understanding of how allelic variation affects gene expression these at level translation. Here report effect natural genetic on transcript protein abundance involved developmental Caenorhabditis elegans. We used selected reaction...
ABSTRACT Fast axonal transport is crucial for neuronal function and driven by kinesins cytoplasmic dynein. Here, we investigated the role of kinesin-1 in dense core vesicle (DCV) C. elegans, using mutants kinesin light chains (klc-1 klc-2) motor subunit (unc-116) expressing an ida-1::gfp transgene that labels DCVs. DCV both directions was greatly impaired unc-116 mutant had reduced velocity a klc-2 mutant. In contrast, speed retrograde increased klc-1 whereas anterograde unaffected. We...
While the Amyloid Precursor Protein (APP) plays a central role in Alzheimer's disease, its cellular function still remains largely unclear. It was our goal to establish APP which will provide insights into APP's implication disease. Using recently developed proteo-liposome assay we established interactome of intracellular domain (known as AICD), thereby identifying novel interactors that mechanistic function. By combining biochemical, cell biological and genetic approaches validated...
Abstract Forty laryngeal carcinomas were studied by immunofluorescence with specific antisera against components of the basement membrane (type IV collagen and laminin) as well connective tissue antigens V fibronectin). The surrounding well‐differentiated squamous cell showed an appearance similar to that seen beneath normal epithelium. In contrast, marked alterations constantly observed around infiltrating poorly‐differentiated carcinomas. staining in most cases was intense mucosa. use...
In high-throughput molecular profiling studies, genotype labels can be wrongly assigned at various experimental steps; the resulting mislabeled samples seriously reduce power to detect genetic basis of phenotypic variation. We have developed an approach potential mislabeling, recover "ideal" and identify "best-matched" for samples. On average, we identified 4% as in eight published datasets, highlighting necessity applying a "data cleaning" step before standard data analysis.
Genetic perturbation in different genetic backgrounds can cause a range of phenotypes within species. These phenotypic differences be the result interaction between background and perturbation. Previously, we reported that gld-1, an important player developmental control Caenorhabditis elegans, released cryptic variation (CGV) affecting fitness backgrounds. Here, investigated change transcriptional architecture. We found 414 genes with cis-expression quantitative trait locus (eQTL) 991...