A5037922922- MicroRNA in disease regulation
- Cancer-related molecular mechanisms research
- Protein Structure and Dynamics
- Lipid Membrane Structure and Behavior
- Nanopore and Nanochannel Transport Studies
- Spectroscopy and Quantum Chemical Studies
- Advanced Electron Microscopy Techniques and Applications
- RNA Research and Splicing
- RNA modifications and cancer
- Electron and X-Ray Spectroscopy Techniques
- Image and Signal Denoising Methods
- Advanced Fluorescence Microscopy Techniques
- Iron Metabolism and Disorders
- Atherosclerosis and Cardiovascular Diseases
- Slime Mold and Myxomycetes Research
- Antimicrobial Peptides and Activities
- Blood properties and coagulation
- stochastic dynamics and bifurcation
- Ion channel regulation and function
- Block Copolymer Self-Assembly
- Gene Regulatory Network Analysis
- Material Dynamics and Properties
- Single-cell and spatial transcriptomics
- Advanced Mathematical Modeling in Engineering
- PI3K/AKT/mTOR signaling in cancer
ETH Zurich
2017-2024
University of Basel
2015-2020
SIB Swiss Institute of Bioinformatics
2015-2020
University of Zurich
2017
University Hospital of Zurich
2017
University of Parma
2017
University of Groningen
2009-2015
University of Freiburg
2013-2014
Wrocław University of Science and Technology
1997
We present an extension of the Martini coarse-grained force field to carbohydrates. The parametrization follows same philosophy as was used previously for lipids and proteins, focusing on reproduction partitioning free energies small compounds between polar nonpolar phases. carbohydrate building blocks considered are monosaccharides glucose fructose disaccharides sucrose, trehalose, maltose, cellobiose, nigerose, laminarabiose, kojibiose, sophorose. Bonded parameters these saccharides...
In this article, we present several algorithms for stochastic dynamics, including Langevin dynamics and different variants of Dissipative Particle Dynamics (DPD), applicable to systems with or without constraints. The are based on the impulsive application friction noise, thus avoiding computational complexity that apply continuous noise. Simulation results thermostat strength diffusion properties ideal gas, coarse-grained (MARTINI) water, constrained atomic (SPC/E) water discussed. We show...
Cell membranes are comprised of multicomponent lipid and protein mixtures that exhibit a complex partitioning behavior. Regions structural compositional heterogeneity play major role in the sorting self-assembly proteins, their clustering into higher-order oligomers. Here, we use computer simulations optical microscopy to study transmembrane helices liquid-disordered domains phase-separated model membranes, irrespective peptide–lipid hydrophobic mismatch. Free energy calculations show...
Hybrid simulations, in which part of the system is represented at atomic resolution and remaining a reduced, coarse-grained, level offer powerful way to combine accuracy associated with atomistic force fields sampling speed obtained coarse-grained (CG) potentials. In this work we introduce straightforward scheme perform hybrid making use virtual sites couple two levels resolution. With help these interactions between molecules different resolution, i.e. CG molecules, are treated same as pure...
Abstract We present an algorithm to reconstruct atomistic structures from their corresponding coarse‐grained (CG) representations and its implementation into the freely available molecular dynamics (MD) program package GROMACS. The central part of is a simulated annealing MD simulation in which CG are coupled via restraints. A number examples demonstrate application reconstruction procedure obtain low‐energy structural ensembles counterparts. reconstructed individual molecules vacuo (NCQ...
Antimicrobial peptides (AMPs) comprise a large family of that include small cationic peptides, such as magainins, which permeabilize lipid membranes. Previous atomistic level simulations magainin-H2 show they act by forming toroidal transmembrane pores. However, due to the description, these were necessarily limited system sizes and sub-microsecond time scales. Here, we study long-time relaxation properties pores evolving systems using coarse-grain (CG) description. The disordered nature...
Intravenous (IV) iron-carbohydrate complexes are widely used nanoparticles (NPs) to treat iron deficiency anaemia, often associated with medical conditions such as chronic kidney disease, heart failure and various inflammatory conditions. Even though a plethora of physicochemical characterisation data clinical studies available for these products, evidence-based correlation between properties outcome has not fully been elucidated yet. Studies on other metal oxide NPs suggest that early...
Low- and high-density lipoproteins (LDL HDL) must pass the endothelial layer to exert pro- antiatherogenic activities, respectively, within vascular wall. However, rate-limiting factors that mediate transendothelial transport of are yet little known. Therefore, we performed a high-throughput screen with kinase drug inhibitors identify modulators LDL HDL transport.Microscopy-based high-content screening was by incubating human aortic cells 141 kinase-inhibiting drugs fluorescent-labeled or...
We quantify the strength of miRNA-target interactions with MIRZA, a recently introduced biophysical model. show that computationally predicted energies interaction correlate strongly estimated from biochemical measurements Michaelis-Menten constants. further accuracy MIRZA model can be improved taking into account emerged experimental data types. In particular, we use chimeric miRNA-mRNA sequences to infer MIRZA-CHIMERA and provide framework for inferring similar rate constants in context...
In multiscale molecular dynamics simulations the accuracy of detailed models is combined with efficiency a reduced representation. For several applications - namely those sampling enhancement it desirable to combine fine-grained (FG) and coarse-grained (CG) approaches into single hybrid approach an adjustable mixing parameter. We present benchmark three algorithms that use two representation layers using Lagrangian formalism. The different for keeping particles at FG level together: 1)...
Article27 August 2018Open Access Transparent process Single-cell mRNA profiling reveals the hierarchical response of miRNA targets to induction Andrzej J Rzepiela Biozentrum, University Basel and Swiss Institute Bioinformatics, Basel, Switzerland Search for more papers by this author Souvik Ghosh orcid.org/0000-0003-4152-4460 Jeremie Breda Arnau Vina-Vilaseca orcid.org/0000-0003-0447-5268 Afzal P Syed Andreas Gruber Katja Eschbach Department Biosystems Science Engineering, ETH Zürich,...
Background: The LDLR (low-density lipoprotein receptor) in the liver is major determinant of LDL-cholesterol levels human plasma. discovery genes that regulate activity helps to identify pathomechanisms hypercholesterolemia and novel therapeutic targets against atherosclerotic cardiovascular disease. Methods: We performed a genome-wide RNA interference screen for limiting uptake fluorescent LDL into Huh-7 hepatocarcinoma cells. Top hit were validated by vitro experiments as well analyses...
Iron deficiency and iron anemia pose significant health challenges worldwide. carbohydrate nanoparticles administered intravenously are a mainstay of treatment to deliver elemental safely effectively. However, despite decades clinical use, complete understanding their physical structure the significance for behavior, particularly at nano-bio interface, is still lacking, underscoring need employ more sophisticated characterization methods. Our study used cryogenic Scanning Transmission...
Based on a given time series, the data-driven Langevin equation proposed by Hegger and Stock [J. Chem. Phys. 130, 034106 (2009)] aims to construct low-dimensional dynamical model of system. Adopting various simple problems biomolecular dynamics, this work presents systematic study theoretical virtues limitations as well practical applicability performance method. As method requires only local information, input data need not be Boltzmann weighted in order warrant that yields correct...
Loss of the tumor suppressor tuberous sclerosis complex 1 ( Tsc1 ) in liver promotes gluconeogenesis and glucose intolerance. We asked whether this could be attributed to aberrant expression small RNAs. performed small-RNA sequencing on -knockout mice, found that miRNAs delta-like homolog Dlk1 )–deiodinase iodothyronine type III Dio3 locus are up-regulated an mTORC1-dependent manner. Sustained mTORC1 signaling during development prevented CpG methylation silencing Dlk1-Dio3 locus, thereby...
Based on a given time series, the data-driven Langevin equation (dLE) estimates drift and diffusion field of dynamics, which are then employed to reproduce essential statistical dynamical features original series. Because propagation dLE requires only local information, input data neither required be Boltzmann weighted nor continuous trajectory. Similar Markov state model, approach therefore holds promise predicting long-time dynamics biomolecular system from relatively short trajectories...
Cryogenic electron microscopy (cryo-EM) is a pivotal technique for imaging macromolecular structures. However, despite extensive processing of large image sets collected in cryo-EM experiments to amplify the signal-to-noise ratio, reconstructed 3D protein-density maps are often limited quality due residual noise, which turn affects accuracy representation. Here, crefDenoiser introduced, denoising neural network model designed enhance signal produced with standard pipelines. The trained...
MiRNAs are post-transcriptional repressors of gene expression that may additionally reduce the cell-to-cell variability in protein expression, induce correlations between target levels and provide a layer through which targets can influence each other's as 'competing RNAs' (ceRNAs). Here we combined single cell sequencing human embryonic kidney cells two distinct miRNAs was induced over wide range, with mathematical modeling, to estimate Michaelis-Menten (KM)-type constants for hundreds...