Publications associées à Phosphorylation of the VAR2CSA extracellular region is associated with enhanced adhesive properties to the placental receptor CSA

Development of multiplexed single-molecule imaging techniques to study chromatin invasion dynamics of chromatin effector proteins

DNA-binding proteins physically interact with the DNA and directly affect genomic functions. The eukaryotic genome is compacted into chromatin, limiting the DNA access to nuclear factors. In this Ph.D. thesis, I explored the dynamic mechanisms, that allow ...

EPFL2023

Potent Virustatic Polymer-Lipid Nanomimics Block Viral Entry and Inhibit Malaria Parasites In Vivo

Francesco Stellacci, Matteo Gasbarri

Infectious diseases continue to pose a substantial burden on global populations, requiring innovative broad-spectrum prophylactic and treatment alternatives. Here, we have designed modular synthetic polymer nanopartides that mimic functional components of ...

AMER CHEMICAL SOC2022

Allosteric control of type I-A CRISPR-Cas3 complexes and establishment as effective nucleic acid detection and human genome editing tools

Henning Paul-Julius Stahlberg, Dongchun Ni

Type I CRISPR-Cas systems typically rely on a two-step process to degrade DNA. First, an RNA-guided complex named Cascade identifies the complementary DNA target. The helicase-nuclease fusion enzyme Cas3 is then recruited in trans for processive DNA degrad ...

CELL PRESS2022

Optogenetic control of Neisseria meningitidis Cas9 genome editing using an engineered, light-switchable anti-CRISPR protein

Bruno Emanuel Ferreira De Sousa Correia, Zander Harteveld, Julius Valten Upmeier Zu Belzen

Optogenetic control of CRISPR-Cas9 systems has significantly improved our ability to perform genome perturbations in living cells with high precision in time and space. As new Cas orthologues with advantageous properties are rapidly being discovered and en ...

2021

NICEdrug.ch, a workflow for rational drug design and systems-level analysis of drug metabolism

Vassily Hatzimanikatis, Noushin Hadadi, Jasmin Maria Hafner, Anush Chiappino-Pepe, Homa Mohammadi Peyhani

The discovery of a drug requires over a decade of intensive research and financial investments – and still has a high risk of failure. To reduce this burden, we developed the NICEdrug.ch resource, which incorporates 250,000 bioactive molecules, and studied ...

2021

A ribonucleoprotein transfection strategy for CRISPR/Cas9-mediated gene editing and single cell cloning in rainbow trout cells

Kristin Schirmer

Background The advent of the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 technology marked the beginning of a new era in the field of molecular biology, allowing the efficient and precise creation of targeted mutations in the ge ...

2021

Constraint-based metabolic control analysis for rational strain engineering

Ljubisa Miskovic, Vassily Hatzimanikatis, Meriç Ataman, Tuure Eelis Hameri, Sofia Tsouka

The advancements in genome editing techniques over the past years have rekindled interest in rational metabolic engineering strategies. While Metabolic Control Analysis (MCA) is a well-established method for quantifying the effects of metabolic engineering ...

2021

Multiplexed Single-Molecule Experiments Reveal Nucleosome Invasion Dynamics of the Cas9 Genome Editor

Louise Catherine Bryan, Beat Fierz, Kristina Makasheva

Single-molecule measurements provide detailed mechanistic insights into molecular processes, for example in genome regulation where DNA access is controlled by nucleosomes and the chromatin machinery. However, real-time single-molecule observations of nucl ...

AMER CHEMICAL SOC2021

Optimization methods and objective functions for analysis of metabolic network models

Zhaleh Hosseini

Computational studies of metabolism aim to systematically analyze the metabolic behaviour of biological systems in different conditions. Genome-scale metabolic network models (GEMs) capture the connection between elements of the network by applying stoichi ...

EPFL2020

EPD in 2020: enhanced data visualization and extension to ncRNA promoters

Philipp Bucher, Giovanna Ambrosini, Romain Fernand Pietro Groux, René Dreos, Patrick Meylan

The Eukaryotic Promoter Database (EPD), available online at https://epd.epfl.ch, provides accurate transcription start site (TSS) information for promoters of 15 model organisms plus corresponding functional genomics data that can be viewed in a genome bro ...

2020

Structures of three MORN repeat proteins and a re-evaluation of the proposed lipid-binding properties of MORN repeats

Charlotte Julie Caroline Gehin

MORN (Membrane Occupation and Recognition Nexus) repeat proteins have a wide taxonomic distribution, being found in both prokaryotes and eukaryotes. Despite this ubiquity, they remain poorly characterised at both a structural and a functional level compare ...

2020

Computational design of anti-CRISPR proteins with improved inhibition potency

Wei Sun, Sandrine Madeleine Suzanne Georgeon, Bruno Emanuel Ferreira De Sousa Correia, Zander Harteveld, Andreas Scheck, Stéphane Rosset, Julius Valten Upmeier Zu Belzen, Yujia Wang

Anti-CRISPR (Acr) proteins are powerful tools to control CRISPR-Cas technologies. However, the available Acr repertoire is limited to naturally occurring variants. Here, we applied structure-based design on AcrIIC1, a broad-spectrum CRISPR-Cas9 inhibitor, ...

NATURE PUBLISHING GROUP2020

KRAB-zinc finger protein gene expansion in response to active retrotransposons in the murine lineage

Didier Trono, Alberto De Iaco

The Krüppel-associated box zinc finger protein (KRAB-ZFP) family diversified in mammals. The majority of human KRAB-ZFPs bind transposable elements (TEs), however, since most TEs are inactive in humans it is unclear whether KRAB-ZFPs emerged to suppress TE ...

2020

Targeting liver stage malaria with metformin

Leonardo Filipe Lemos Rocha

Despite an unprecedented 2 decades of success, the combat against malaria - the mosquito-transmitted disease caused by Plasmodium parasites - is no longer progressing. Efforts toward eradication are threatened by the lack of an effective vaccine and a rise ...

2019

Genome-Scale Identification of Essential Metabolic Processes for Targeting the Plasmodium Liver Stage

Vassily Hatzimanikatis, Dominique Soldati-Favre, Anush Chiappino-Pepe, Vikash Kumar Pandey

Plasmodium gene functions in mosquito and liver stages remain poorly characterized due to limitations in the throughput of phenotyping at these stages. To fill this gap, we followed more than 1,300 barcoded P. berghei mutants through the life cycle. We dis ...

2019

A new approach to Cas9-based genome editing in Aspergillus niger that is precise, efficient and selectable

Laure Marie Colette Leynaud-Kieffer Curran

Aspergillus niger and other filamentous fungi are widely used in industry, but efficient genetic engineering of these hosts remains nascent. For example, while molecular genetic tools have been developed, including CRISPR/Cas9, facile genome engineering of ...

2019

Analysis of cellular and drug action mechanisms in the malaria parasites using systems biology approaches

Anush Chiappino-Pepe

Malaria puts at risk of infection half of the world population and still kills around half a million people every year. The rapid and worrisome rise of drug-resistant malaria parasites hinders the treatment of malaria and calls for a global collaboration t ...

EPFL2018

Recent Advances of Malaria Parasites Detection Systems Based on Mathematical Morphology

Michel Kocher

Malaria is an epidemic health disease and a rapid, accurate diagnosis is necessary for proper intervention. Generally, pathologists visually examine blood stained slides for malaria diagnosis. Nevertheless, this kind of visual inspection is subjective, err ...

2018

Engineered anti-CRISPR proteins for optogenetic control of CRISPR-Cas9

Bruno Emanuel Ferreira De Sousa Correia, Zander Harteveld

Anti-CRISPR proteins are powerful tools for CRISPR-Cas9 regulation; the ability to precisely modulate their activity could facilitate spatiotemporally confined genome perturbations and uncover fundamental aspects of CRISPR biology. We engineered optogeneti ...

NATURE PUBLISHING GROUP2018

Bioenergetics-based modeling of Plasmodium falciparum metabolism reveals its essential genes, nutritional requirements, and thermodynamic bottlenecks

Vassily Hatzimanikatis, Stepan Tymoshenko, Dominique Soldati-Favre, Meriç Ataman, Anush Chiappino-Pepe

Novel antimalarial therapies are urgently needed for the fight against drug-resistant para- sites. The metabolism of malaria parasites in infected cells is an attractive source of drug targets but is rather complex. Computational methods can handle this co ...

Public Library of Science2017