A5033775526- Genetic and Kidney Cyst Diseases
- Protist diversity and phylogeny
- Renal and related cancers
- Single-cell and spatial transcriptomics
- Pluripotent Stem Cells Research
- Algal biology and biofuel production
- Congenital heart defects research
- Genetics and Neurodevelopmental Disorders
- CRISPR and Genetic Engineering
- Microtubule and mitosis dynamics
- Epigenetics and DNA Methylation
- Regulation of Appetite and Obesity
- Biochemical Analysis and Sensing Techniques
- Gene expression and cancer classification
- RNA regulation and disease
- Genomics and Rare Diseases
- melanin and skin pigmentation
- Birth, Development, and Health
- Micro and Nano Robotics
- Genetic Syndromes and Imprinting
- 3D Printing in Biomedical Research
- Cardiomyopathy and Myosin Studies
- Neuroscience and Neural Engineering
Open Targets
2018-2023
Wellcome Sanger Institute
2018-2021
Université Claude Bernard Lyon 1
2012-2020
Institut NeuroMyoGène
2019-2020
Inserm
2019-2020
Centre National de la Recherche Scientifique
2012-2020
Wellcome/MRC Cambridge Stem Cell Institute
2018
University of Cambridge
2018
Medical Research Council
2018
University of California, San Diego
2014-2016
Dendritic spines represent the major site of neuronal activity in brain; they serve as receiving point for neurotransmitters and undergo rapid activity-dependent morphological changes that correlate with learning memory. Using a combination homozygosity mapping next-generation sequencing two consanguineous families affected by nonsyndromic autosomal-recessive intellectual disability, we identified truncating mutations formin 2 (FMN2), encoding protein belongs to family actin cytoskeleton...
Abstract Cilia assembly is under strict transcriptional control during animal development. In vertebrates, a hierarchy of transcription factors (TFs) are involved in controlling the specification, differentiation and function multiciliated epithelia. RFX TFs play key functions ciliogenesis animals. Whereas only one factor regulates C. elegans, several distinct have been implicated this process vertebrates. However, clear understanding specific redundant different ciliated cells remains...
Cilia are evolutionarily conserved organelles endowed with essential physiological and developmental functions. In humans, disruption of cilia motility or signaling leads to complex pleiotropic genetic disorders called ciliopathies. requires the assembly multi-subunit motile components such as dynein arms, but mechanisms underlying their pathway transport into axoneme still largely unknown. We identified a previously uncharacterized coiled-coil domain containing protein CCDC151, which is in...
The use of induced pluripotent stem cells (iPSC) as models for development and human disease has enabled the study otherwise inaccessible tissues. A remaining challenge in developing reliable is our limited understanding factors driving irregular differentiation iPSCs, particularly impact acquired somatic mutations. We leveraged data from a pooled dopaminergic neuron experiment 238 iPSC lines profiled with single-cell RNA whole-exome sequencing to how mutations affect outcomes. found that...
The lack of pro-opiomelanocortin (POMC)-derived melanocortin peptides results in hypoadrenalism and severe obesity both humans rodents that is treatable with synthetic melanocortins. However, there are significant differences POMC processing between rodents, little known about the relative physiological importance products human brain. aim this study was to determine which POMC-derived present brain, establish their concentrations, test if production dynamically regulated.We analysed fresh...
Cilia and flagella are conserved eukaryotic organelles essential for cellular signaling motility. dysfunctions cause life-threatening ciliopathies, many of which due to defects in the transition zone (TZ), a complex structure ciliary base. Therefore, understanding TZ assembly, relies on ordered interactions multiprotein modules, is critical importance. Here, we show that Drosophila Dzip1 Fam92 form functional module constrains core protein, Cep290, We identify cell type specific roles this...
Abstract Common genetic variants can have profound effects on cellular function, but studying these in primary human tissue samples and during development is challenging. Human induced pluripotent stem cell (iPSC) technology holds great promise for assessing across different differentiation contexts. Here, we use an efficient pooling strategy to differentiate 215 iPS lines towards a midbrain neural fate, including dopaminergic neurons, profile over 1 million cells sampled three timepoints...
In this paper we assess the role of protein MKS1 (Meckel syndrome type 1) in cortical membrane mechanics ciliated protist Paramecium. This is known to be crucial process cilium formation, and investigate its putative membrane–cytoskeleton attachment. Therefore, compare cells where gene coding for silenced wild-type cells. We found that scanning electron microscopy observation cell surface reveals a cup-like structure lost Since based on underlying cytoskeleton, one hypothesis explain...
This protocol outlines a method for dissociating human pluripotent stem cell-derived neuronal culture to single cells loading onto Chromium 10x chip cell RNA-sequencing. makes distinction between early progenitors and mature cultures, as additional steps reagents are required in order sufficiently dissociate the latter. These include: - DNase Vial (D2) PDS Kit Papain Note: In our labs, iPS were undergoing 52-day long differentiation process dopaminergic neurons (adapted from...
The dopaminergic system has key roles in human physiology and is implicated a broad range of neurological neuropsychiatric conditions that are increasingly investigated using induced pluripotent stem cell-derived midbrain models. To determine the similarity such models to systems, we undertook single cell spatial profiling first second trimester fetal compared it vitro Our initial histological analysis revealed structural complexity already similar adult tissue, although this did not fully...
Abstract The use of induced pluripotent stem cells (iPSC) as models for development and human disease has enabled the study otherwise inaccessible tissues. A remaining challenge in developing reliable is our limited understanding factors driving irregular vitro differentiation iPSCs, particularly impact acquired somatic mutations. We leveraged data from a pooled dopaminergic neuron experiment 238 iPSC lines profiled with single-cell whole-exome sequencing to how mutations affect outcomes....
Mutations in the protein MKS1 cause severe developmental disorders such as Meckel-Gruber syndrome (MKS). Dysfunctional caused a panel of cellular defects ranging from abortive centriolar migration to ciliary instability and defective signaling [1-3]. Most analyses converge conclusion that vertebrates, depletion leads impairment Hh Wnt pathways [4-9]. Accordingly, has been shown be localized at transition zone such, involved membrane composition [6]. By combining two complementary cell...
Cilia are highly conserved structures found from protozoa to mammals where they play major functions in motility and sensation. Ciliary dysfunction leads a variety of human genetic diseases called ciliopathies. RFX transcription factors key players regulating genes involved cilia assembly C. elegans mammals. Using genomic screen identify targets RFX, we selected novel gene, noni, potentially implicated biology. No known function has been described for this which is specific ciliated species....
This protocol describes a method for the production of dopaminergic neurons from human iPSCs, using 52-day long differentiation adapted doi.org/10.1038/nature10648. Steps in this assume use single 12 well plate purposes differentiation; adjust volumes accordingly depending on labware used.