A5047577595- Cellular Mechanics and Interactions
- Genomics and Chromatin Dynamics
- Nuclear Structure and Function
- RNA Research and Splicing
- Microtubule and mitosis dynamics
- Force Microscopy Techniques and Applications
- Cell Image Analysis Techniques
- Single-cell and spatial transcriptomics
- DNA and Nucleic Acid Chemistry
- RNA Interference and Gene Delivery
- Agricultural pest management studies
- 3D Printing in Biomedical Research
- Epigenetics and DNA Methylation
- Genetics and Plant Breeding
- DNA Repair Mechanisms
- Acute Myeloid Leukemia Research
- Micro and Nano Robotics
- Genetic and Environmental Crop Studies
- Legume Nitrogen Fixing Symbiosis
- RNA and protein synthesis mechanisms
- Microfluidic and Bio-sensing Technologies
- Cancer Cells and Metastasis
- Advanced Fluorescence Microscopy Techniques
- Plant Genetic and Mutation Studies
- Plant Virus Research Studies
ETH Zurich
2020-2025
Paul Scherrer Institute
2020-2025
IFOM
2015-2022
National University of Singapore
2012-2021
Singapore-MIT Alliance for Research and Technology
2014-2018
Joint Research Center
2016
National Centre for Biological Sciences
2004-2014
A*STAR-NUS Clinical Imaging Research Centre
2014
Tata Institute of Fundamental Research
2002-2012
Raman Research Institute
2003-2009
Physical forces in the form of substrate rigidity or geometrical constraints have been shown to alter gene expression profile and differentiation programs. However, underlying mechanism regulation by these mechanical cues is largely unknown. In this work, we use micropatterned substrates cellular geometry (shape, aspect ratio, size) study nuclear mechanotransduction regulate expression. Genome-wide transcriptome analysis revealed cell geometry-dependent alterations actin-related Increase...
ATR controls chromosome integrity and chromatin dynamics. We have previously shown that yeast Mec1/ATR promotes detachment from the nuclear envelope to counteract aberrant topological transitions during DNA replication. Here, we provide evidence activity at responds mechanical stress. Human associates with S phase prophase, both osmotic stress stretching relocalize membranes throughout cell cycle. The ATR-mediated response occurs within range of physiological forces, is reversible,...
Significance Growing evidence suggests that cytoskeleton-mediated transmission of mechanical forces from the extracellular matrix (ECM) to nucleus alters nuclear mechanics and architecture these alterations can, in turn, impact ability cell respond its microenvironment by regulating important functions including gene expression both normal diseased cells. Using a chemomechanical model together with micropatterning experiments, we elucidate how physical properties mechanisms through which are...
Significance Physical properties of the cell nucleus are important for various cellular functions. However, role geometry and active cytoskeletal forces in regulating nuclear dynamics chromatin is not well understood. Our results show cells with reduced matrix constraints have short actomyosin structures. These dynamic structures together lower lamin A/C levels, resulting softer nuclei, may provide driving force fluctuations. Furthermore, we observed increased heterochromatin telomere under...
Abstract The development of single-cell methods for capturing different data modalities including imaging and sequencing has revolutionized our ability to identify heterogeneous cell states. Different provide perspectives on a population cells, their integration is critical studying cellular heterogeneity its function. While various have been proposed integrate modalities, coupling an open challenge. We here present approach integrating vastly by learning probabilistic between the using...
Significance We identify a set of unique biophysical markers multipotent mesenchymal stromal cell populations. Multivariate analysis cells from 10 adult and fetal bone marrow donors shows that distinct subpopulations exist within supposed stem populations are otherwise indistinguishable by accepted marker surface antigens. find although no single parameter is wholly predictive multipotency, three these together—cell diameter, mechanical stiffness, nuclear membrane fluctuations—distinguish...
Fibroblasts exhibit heterogeneous cell geometries in tissues and integrate both mechanical biochemical signals their local microenvironment to regulate genomic programs via chromatin remodelling. While connective fibroblasts experience tensile compressive forces (CFs), the role of regulating behavior and, particular, impact geometry modulating transcriptional response such extrinsic is unclear. Here we show that CF on geometrically well-defined mouse fibroblast cells reduces actomyosin...
Significance Cells can sense and adapt to their physical microenvironment through specific mechanosensing mechanisms. These properties are often mediated by the actin cytoskeleton, which be affected a wide range of forces, including fluid shear stress, cyclic stretch, optical or magnetic force. However, immediate effects force on assembly structures distal from sites application were not assessed. Our work reveals previously unidentified structure, perinuclear rim, is induced mechanical...
Extracellular matrix signals from the microenvironment regulate gene expression patterns and cell behavior. Using a combination of experiments geometric models, we demonstrate correlations between geometry, three-dimensional (3D) organization chromosome territories, expression. Fluorescence in situ hybridization showed that micropatterned fibroblasts cultured on anisotropic versus isotropic substrates resulted repositioning specific chromosomes, which contained genes were differentially...
Significance The mechanical reprogramming of fibroblasts, followed by their redifferentiation into rejuvenated fibroblasts in an optimized 3D collagen matrix, made these cells more contractile and efficient at synthesizing matrix components including laminin, fibronectin, collagen-IV. Moreover, the obtained through this approach exhibited a decrease DNA damage. derived from method precisely align tissue architectures, suggesting its potential application as clinical implants engineering...
Tissue development and disease lead to changes in cellular organization, nuclear morphology, gene expression, which can be jointly measured by spatial transcriptomic technologies. However, methods for analyzing the different data modalities 3D are still lacking. We present a computational framework integrate Spatial Transcriptomic using over-parameterized graph-based Autoencoders with Chromatin Imaging (STACI) identify molecular functional alterations tissues. STACI incorporates multiple...
More than 1200 cultivars, breeding lines, and wild species of Lycopersicon were screened for resistance to the tomato leaf curl virus under field conditions. All accessions esculentum found susceptible virus. Three lines hirsutum one peruvianum showed apparent owing failure transmission by whiteflies. Morphological analysis light scanning electron microscopy revealed distributions different types trichomes on surfaces. proved be least affected because it did not support whitefly infestation...
Nuclear shape and size are emerging as mechanistic regulators of genome function. Yet, the coupling between chromatin assembly various nuclear cytoplasmic scaffolds is poorly understood. The present work explores structural organization a prestressed nucleus in variety cellular systems ranging from cells culture to those an organism. A combination laser ablation perturbations was used decipher dynamic nature nucleo-cytoplasmic contacts. In primary mouse embryonic fibroblasts, heterochromatin...