A5021638908- Nuclear Structure and Function
- RNA Research and Splicing
- Autophagy in Disease and Therapy
- RNA regulation and disease
- DNA Repair Mechanisms
- Herpesvirus Infections and Treatments
- Mosquito-borne diseases and control
- RNA Interference and Gene Delivery
- Skin and Cellular Biology Research
- Cellular Mechanics and Interactions
- Microtubule and mitosis dynamics
- CRISPR and Genetic Engineering
- Toxin Mechanisms and Immunotoxins
- Virus-based gene therapy research
- Science, Research, and Medicine
- Glycosylation and Glycoproteins Research
- RNA modifications and cancer
- Graphite, nuclear technology, radiation studies
- Bacteriophages and microbial interactions
- Cytomegalovirus and herpesvirus research
- Toxoplasma gondii Research Studies
- Cell Adhesion Molecules Research
- Cellular transport and secretion
- interferon and immune responses
- Cardiomyopathy and Myosin Studies
University of Cambridge
2015-2025
Utrecht University
2016-2021
Wageningen University & Research
2014
Nestor-Guillermo progeria syndrome (NGPS) is caused by a homozygous alanine-to-threonine mutation at position 12 (A12T) in barrier-to-autointegration factor (BAF). It characterized accelerated aging with severe skeletal abnormalities. BAF an essential protein binding to DNA and nuclear envelope (NE) proteins, involved NE rupture repair. Here, we assessed the impact of A12T on integrity using NGPS-derived patient fibroblasts. We observed strong defect lamin A/C accumulation ruptures NGPS...
Herpes simplex virus-1 (HSV-1) is a large enveloped DNA virus that belongs to the family of Herpesviridae. It has been recently shown cytoplasmic membranes wrap newly assembled capsids are endocytic compartments derived from plasma membrane. Here, we show dynamin-dependent endocytosis plays major role in this process. Dominant-negative dynamin and clathrin adaptor AP180 significantly decrease production. Moreover, inhibitors targeting lead decreased transport glycoproteins capsids,...
The nuclear envelope (NE) is important for cellular health as it protects and organizes the genome. NE dynamics various processes including cell growth, migration removal of defective components. In extreme cases, can rupture leading to exchange material between interior cytoplasm. Rapid repair initiated minimize effect on While our understanding machinery involved in this process increasing, a lot still unknown about events up rupture. Interestingly, biomolecular condensates have recently...
Progeria syndromes are very rare, incurable premature aging conditions recapitulating most features. Here, we report a whole genome, multiparametric CRISPR screen, identifying 43 genes that can rescue multiple cellular phenotypes associated with progeria. We implement the screen in fibroblasts from Néstor-Guillermo Syndrome male patients, carrying homozygous A12T mutation BAF. The hits enriched for involved protein synthesis, and RNA transport osteoclast formation validated whole-organism...
The selective transport of different cargoes into axons and dendrites underlies the polarized organization neuron. Although it has become clear that combined activity motors determines destination selectivity transport, little is known about mechanistic details motor cooperation. For example, exact role myosin-V in opposing microtubule-based axon entries remained unclear. Here we use two orthogonal chemically-induced heterodimerization systems to independently recruit cargoes. We find...
Selective types of autophagy mediate the clearance specific cellular components and are essential to maintain homeostasis. However, tools directly induce monitor such pathways limited. Here we introduce PIM (particles induced by multimerization) assay as a tool for study aggrephagy, autophagic aggregates. The uses an inducible multimerization module assemble protein clusters, which upon induction recruit ubiquitin, p62, LC3 before being delivered lysosomes. Moreover, use dual fluorescent tag...
Nuclear blebs are herniations of the nucleus that occur in diseased nuclei cause nuclear rupture leading to cellular dysfunction. Chromatin and lamins two major structural components maintain its shape function, but their relative roles blebbing remain elusive. Lamin B is reported be lost by qualitative data while quantitative studies reveal a spectrum lamin levels dependent on perturbation cell type. has been decreased or de-compacted blebs, again not conclusive. To determine composition we...
Nuclear blebs are herniations of the nucleus that occur in diseased nuclei cause nuclear rupture leading to cellular dysfunction. Chromatin and lamins two major structural components maintain its shape function, but their relative roles blebbing remain elusive. To determine composition blebs, we compared immunofluorescence intensity DNA lamin B main body bleb across cell types perturbations. density was consistently decreased about half while levels varied widely. Partial Wave Spectroscopic...
Degradation of aggregates by selective autophagy is important as damaged proteins may impose a threat to cellular homeostasis. Although the core components machinery are well characterized, spatiotemporal regulation many processes, including aggrephagy, remains largely unexplored. Furthermore, because most live-cell imaging studies have so far focused on starvation-induced autophagy, little known about dynamics aggrephagy. Here, we describe development and application mKeima-PIM assay, which...
Abstract Progeria syndromes are very rare, incurable premature aging conditions recapitulating most features. Here, we report the first whole genome, multiparametric CRISPR anti-aging screen, identifying 43 new genes that can reverse multiple phenotypes in progeria. The screen was implemented fibroblasts from Néstor- Guillermo Syndrome (NGPS) patients, carrying a homozygous p.Ala12Thr mutation barrier-to-autointegration factor (BAF A12T). hits were enriched for involved protein translation,...
Cockayne syndrome (CS) is a premature ageing condition characterized by microcephaly, growth failure, and neurodegeneration. It caused mutations in ERCC6 or ERCC8 encoding for B (CSB) A (CSA) proteins, respectively. CSA CSB have well-characterized roles transcription-coupled nucleotide excision repair, responsible removing bulky DNA lesions, including those UV irradiation. Here, we report that dysfunction causes defects the nuclear envelope (NE) integrity. NE characteristic of progeroid...
Progeria syndromes are very rare, incurable premature aging conditions recapitulating most features. Here, we report the first whole genome, multiparametric CRISPR anti-aging screen, identifying 43 new genes that can reverse multiple phenotypes in progeria. The screen was implemented fibroblasts from Nestor-Guillermo Syndrome (NGPS) patients, carrying a homozygous p.Ala12Thr mutation barrier-to-autointegration factor (BAF A12T). hits were enriched for involved protein translation, and RNA...
Familial partial lipodystrophy type 2 is an autosomal dominant disorder generally due to heterozygous missense variants in the LMNA gene.In women, phenotype begins manifest before puberty, while men onset later.It striking that most of cases reported literature are women.Specifically, our cohort only 27% these patients were men.Considering pattern inheritance disease where a similar ratio between males and females would be expected, it obvious majority with this do not they diagnosed.The...
Abstract Cockayne syndrome (CS) is an autosomal recessive premature ageing condition mainly characterized by microcephaly, growth failure, and neurodegeneration. It caused mutations in ERCC6 or ERCC8 genes which encode for Syndrome B (CSB) A (CSA) proteins, respectively. CSA CSB have well-characterised roles transcription-coupled nucleotide excision repair (TC-NER), responsible the removal of bulky DNA lesions, including those UV irradiation. Here, we report that knockout cells patient...
Abstract The premature aging disorder Nestor Guillermo Progeria Syndrome (NGPS) is caused by a homozygous Alanine to Threonine mutation at position 12 (A12T) in Barrier-to- Autointegration Factor (BAF). BAF small essential protein that binds DNA and nuclear envelope proteins. It contributes important cellular processes including transcription regulation reformation after mitosis. More recently, was identified as an factor for repair upon rupture interphase. However, the mechanism which A12T...
ABSTRACT Degradation of aggregates by selective autophagy is important as damaged proteins may impose a threat to cellular homeostasis. Although the core components machinery are well-characterized, spatiotemporal regulation many processes, including aggrephagy, remains largely unexplored. Furthermore, because most live-cell imaging studies have so far focused on starvation-induced autophagy, little known about dynamics aggrephagy. Here, we describe development and application mKeima-PIM...