A5080580420- Genetic and Kidney Cyst Diseases
- Microtubule and mitosis dynamics
- Protist diversity and phylogeny
- Lipid metabolism and biosynthesis
- Renal and related cancers
- Lipid Membrane Structure and Behavior
- Bioinformatics and Genomic Networks
- Biomedical Text Mining and Ontologies
- Neonatal Respiratory Health Research
- Genomics and Rare Diseases
- Caveolin-1 and cellular processes
- RNA Interference and Gene Delivery
- Cancer-related molecular mechanisms research
- Autophagy in Disease and Therapy
- Ubiquitin and proteasome pathways
- Wound Healing and Treatments
- RNA modifications and cancer
- Immune cells in cancer
- Hedgehog Signaling Pathway Studies
- Photosynthetic Processes and Mechanisms
- Skin Protection and Aging
- RNA Research and Splicing
- Histone Deacetylase Inhibitors Research
- Pluripotent Stem Cells Research
- Signaling Pathways in Disease
King's College London
2020-2024
Cell Therapy Catapult
2023
Guy's Hospital
2023
Cell and Gene Therapy Catapult
2023
Centro de Biología Molecular Severo Ochoa
2012-2022
Universidad Autónoma de Madrid
2012-2022
Consejo Superior de Investigaciones Científicas
2012-2022
National Institutes of Health
2012
The primary cilium is a membrane protrusion that crucial for vertebrate tissue homeostasis and development. Here, we investigated the uncharacterized process of ciliogenesis in polarized epithelial cells. We show after cytokinesis, midbody inherited by one daughter cells as remnant initially locates peripherally at apical surface then moves along and, once proximal to centrosome center surface, enables formation. physical removal greatly impairs ciliogenesis. developed probabilistic cell...
The endothelium maintains a barrier between blood and tissue that becomes more permeable during inflammation. Membrane rafts are ordered assemblies of cholesterol, glycolipids, proteins modulate proinflammatory cell signaling function. In epithelial cells, the MAL family members MAL, MAL2, myeloid-associated differentiation marker (MYADM) regulate function dynamics membrane domains. We analyzed expression these three in human endothelial cells found only MYADM is expressed. was confined...
The role of formins in microtubules is not well understood. In this study, we have investigated the mechanism by which INF2, a formin mutated degenerative renal and neurological hereditary disorders, controls microtubule acetylation. We found that silencing INF2 epithelial RPE-1 cells produced dramatic drop tubulin acetylation, increased G-actin/F-actin ratio, impaired myocardin-related transcription factor (MRTF)/serum response (SRF)-dependent transcription, known to be repressed levels...
Abstract The primary cilium is a single non-motile protrusion of the plasma membrane most types mammalian cell. structure, length and function must be tightly controlled because their dysfunction associated with disease. Caveolin 1 (Cav1), which best known as component invaginations called caveolae, also present in non-caveolar domains whose beginning to understood. We show that silencing α β Cav1 isoforms different cell lines increases ciliary regardless route ciliogenesis. sole expression...
Dedifferentiation is the process by which terminally differentiated cells acquire properties of stem cells. During mouse skin wound healing, Gata6-lineage positive sebaceous duct are able to dedifferentiate. Here we have integrated lineage tracing and single-cell mRNA sequencing uncover underlying mechanism. negative epidermal in wounds transcriptionally indistinguishable. Furthermore, contrast reprogramming induced pluripotent cells, same genes expressed dedifferentiation differentiation...
The base of the primary cilium contains a zone condensed membranes whose importance is not known. Here, we have studied involvement MAL, tetraspanning protein that exclusively partitions into membrane fractions, in condensation at ciliary and investigated these formation. We show MAL accumulates epithelial MDCK cells. Knockdown expression resulted drastic reduction base, percentage ciliated cells length cilia, but did affect docking centrosome to plasma or produce missorting proteins...
Abstract Lipid liquid–liquid immiscibility and its consequent lateral heterogeneity have been observed under thermodynamic equilibrium in model native membranes. However, cholesterol‐rich membrane domains, sometimes referred to as lipid rafts, are difficult observe spatiotemporally live cells. Despite their importance many biological processes, robust evidence for existence remains elusive. This is mainly due the difficulty simultaneously determining chemical composition physicochemical...
Abstract Cohort-wide sequencing studies have revealed that the largest category of variants is those deemed ‘rare’, even for subset located in coding regions (99% known are seen less than 1% population. Associative methods give some understanding how rare genetic influence disease and organism-level phenotypes. But here we show additional discoveries can be made through a knowledge-based approach using protein domains ontologies (function phenotype) considers all regardless allele frequency....
The inheritance of the midbody remnant (MBR) breaks symmetry two daughter cells, with functional consequences for lumen and primary cilium formation by polarized epithelial also development differentiation. However, despite its importance, neither relationship between plasma membrane inherited MBR nor mechanism is well known. Here, analysis correlative light ultra-high-resolution scanning electron microscopy reveals a membranous stalk that physically connects to apical cells. stalk, which...
Abstract The primary cilium is a specialized plasma membrane protrusion that harbors receptors involved in important signaling pathways. Despite its central role regulating cellular behavior, the biogenesis of not fully understood. In fact, source ciliary remains mystery cell types assemble their entirely at surface, such as polarized renal epithelial cells. After cytokinesis, remnant midbody these cells moves to center apical where it licenses centrosome for ciliogenesis through an...
Oral squamous cell carcinoma (OSCC) is a subtype of head and neck cancer that arises in the multilayered epithelia mouth lips. Although inactivating mutations CASP8 are frequently found human OSCC their role disease unknown. To investigate this, we deleted Casp8 oral epithelium adult mice. Loss Caspase-8 resulted defects tongue epithelial barrier triggered neutrophil-rich immune infiltrate distinct from observed on epidermal deletion. deletion led to activation autophagy. Inhibition...
In polarised epithelial cells the midbody forms at apical cell surface during cytokinesis. Once severed, is inherited by one of daughter remaining tethered to plasma membrane where it participates in non-cytokinetic processes, such as primary ciliogenesis. Here, we describe a novel method physically remove remnant from and assess possible effects caused its loss (Bernabé- Rubio et al., 2016 ).
Proteolipids are proteins with unusual lipid-like properties. It has long been established that PLP and plasmolipin, which two unrelated membrane-tetra-spanning myelin proteolipids, can be converted in vitro into a water-soluble form distinct conformation, raising the question of whether these, or other similar adopt different conformations cell to adapt their structure environments. Here, we show MALL, another proteolipid structure, distributes membranes outside nucleus and, within nucleus,...
Summary Cohort-wide sequencing studies have revealed that the largest category of variants is those deemed ‘rare’, even for subset located in coding regions (99% known are seen less than 1% population 1–3 ). Our understanding how rare genetic influence disease and organism-level phenotypes has achieved limited progress, partly explained by intrinsic difficulty statistically evaluating biological significance events. Here we show discoveries can instead be made through a knowledge-based...
Abstract The inheritance of the midbody remnant (MBR) breaks symmetry two daughter cells, with functional consequences for lumen and primary cilium formation by polarized epithelial also development differentiation. However, despite their importance, neither relationship between plasma membrane inherited MBR nor mechanism is well known. Here, analysis correlative light ultra-high-resolution scanning electron microscopy reveals a membranous stalk that physically connects to apical cells....
Abstract The primary cilium is a specialized plasma membrane protrusion with important receptors for signalling pathways. In polarized epithelial cells, the assembles after midbody remnant (MBR) encounters centrosome at apical surface. surrounding MBR, namely associated patch (RAMP) once situated next to centrosome, releases some of its lipid components form centrosome-associated (CAMP) from which ciliary stems. RAMP undergoes spatiotemporal refinement during formation CAMP, becomes highly...