Publications related to Gene targeting

Evaluation of genetic demultiplexing of single-cell sequencing data from model species

Single-cell sequencing (sc-seq) provides a species agnostic tool to study cellular processes. However, these technologies are expensive and require sufficient cell quantities and biological replicates to avoid artifactual results. An option to address thes ...

LIFE SCIENCE ALLIANCE LLC2023

Achieving high hybridization density at DNA biosensor surfaces using branched spacer and click chemistry

Sandrine Gerber, Alireza Kavand, Mounir Driss Mensi, Lucas Mayoraz, Perrine Agnes Edith Robin

The COVID-19 pandemic has highlighted the necessity to develop fast, highly sensitive and selective virus detection methods. Surface-based DNA-biosensors are interesting candidates for this purpose. Functionalization of solid substrates with DNA must be pr ...

2023

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

Kristina Makasheva

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

Tailoring the Hybridization Density of DNA Biosensors through Tunable Surface Functionalization

Sandrine Gerber, Mounir Driss Mensi, Pauline Skigin, Perrine Agnes Edith Robin, Lucas Mayoraz

DNA biosensors are promising candidates for the development of point-of-care diagnosis methods. They can be inserted in microfluidic platforms, are often non-expensive, and can be produced for a variety of targeted analytes. However, their development face ...

Wiley-VHCA AG2023

Identifying genetic and dietary modulators of metabolic disorders using systems genetics

Xiaoxu Li

Long-term consumption of lipid-rich foods can contribute to common metabolic diseases and systemic low-grade inflammation. However, dietary responses and the development of non-communicable diseases are shaped by genetic factors and gene-by-environment int ...

EPFL2023

Wide-scale identification of novel/eliminated genes responsible for evolutionary transformations

Daria Korotkova

BackgroundIt is generally accepted that most evolutionary transformations at the phenotype level are associated either with rearrangements of genomic regulatory elements, which control the activity of gene networks, or with changes in the amino acid conten ...

2023

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

Engineering synthetic adhesins for biophysical investigation and rewiring of host-microbe interactions

Xavier Jean-Yves Pierrat

Host attachment is often a critical step in the onset of pathogenesis. To attach to host cells, bacteria have evolved a range of adhesins that bind to specific receptors. Some of these adhesins have been thoroughly characterized using biochemical technique ...

EPFL2022

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

The makings of TERRA R-loops at chromosome ends

Joachim Lingner, Marianna Feretzaki, Rita Valador Fernandes

Telomeres protect chromosome ends from nucleolytic degradation, uncontrolled recombination by DNA repair enzymes and checkpoint signaling, and they provide mechanisms for their maintenance by semiconservative DNA replication, telomerase and homologous reco ...

TAYLOR & FRANCIS INC2021

Human shelterin protein POT1 prevents severe telomere instability induced by homology-directed DNA repair

Joachim Lingner, Galina Glousker, Anna-Sophia Briod

The evolutionarily conserved POT1 protein binds single-stranded G-rich telomeric DNA and has been implicated in contributing to telomeric DNA maintenance and the suppression of DNA damage checkpoint signaling. Here, we explore human POT1 function through g ...

WILEY2020

Transcription Factors and DNA Play Hide and Seek

David Michael Suter

Transcription factors (TFs) bind to specific DNA motifs to regulate the expression of target genes. To reach their binding sites, TFs diffuse in 3D and perform local motions such as 1D sliding, hopping, or intersegmental transfer. TF-DNA interactions depen ...

2020

Assessing Public Opinion on CRISPR-Cas9: Combining Crowdsourcing and Deep Learning

Marcel Salathé, Martin Mathias Müller, Martin Müller

Background: The discovery of the CRISPR-Cas9-based gene editing method has opened unprecedented new potential for biological and medical engineering, sparking a growing public debate on both the potential and dangers of CRISPR applications. Given the speed ...

JMIR PUBLICATIONS, INC2020

Skeletal muscle enhancer interactions identify genes controlling whole-body metabolism

Johan Auwerx, Martin Rainer Wohlwend

Obesity and type 2 diabetes (T2D) are metabolic disorders influenced by lifestyle and genetic factors that are characterized by insulin resistance in skeletal muscle, a prominent site of glucose disposal. Numerous genetic variants have been associated with ...

Nature Research2020

Bile Acids Signal via TGR5 to Activate Intestinal Stem Cells and Epithelial Regeneration

Kristina Schoonjans, Alessia Perino, Maroun Bou Sleiman, Giovanni Sorrentino, Ece Yildiz, Gaby El Alam

BACKGROUND & AIMS: Renewal and patterning of the intestinal epithelium is coordinated by intestinal stem cells (ISCs); dietary and metabolic factors provide signals to the niche that control ISC activity. Bile acids (BAs), metabolites in the gut, signal nu ...

2020

Overexpression of transcription factor Foxa1 and target genes remediate therapeutic protein production bottlenecks in Chinese hamster ovary cells

Nicolas Mermod, Iris Bodenmann

Despite extensive research conducted to increase protein production from Chinese hamster ovary (CHO) cells, cellular bottlenecks often remain, hindering high yields. In this study, a transcriptomic analysis led to the identification of 32 genes that are co ...

WILEY2020

DPPA2 and DPPA4 are necessary to establish a 2C‐like state in mouse embryonic stem cells

Didier Trono, Julien Léonard Duc, Alexandre Coudray, Alberto De Iaco

After fertilization of the transcriptionally silent oocyte, expression from both parental chromosomes is launched through zygotic genome activation (ZGA), occurring in the mouse at the 2-cell (2C) stage. Among the first elements to be transcribed are the D ...

2019

Impact of genome architecture on the functional activation and repression of Hox regulatory landscapes

Denis Duboule, Lucille Delisle, Edgardo Rodriguez Carballo, Nayuta Yakushiji

Background The spatial organization of the mammalian genome relies upon the formation of chromatin domains of various scales. At the level of gene regulation in cis, collections of enhancer sequences define large regulatory landscapes that usually match wi ...

2019

Gene Editing Preserves Visual Functions in a Mouse Model of Retinal Degeneration

Diego Ghezzi, Naïg Aurelia Ludmilla Chenais, Paola Vagni, Tommaso Marchetti

Inherited retinal dystrophies (IRDs) are a large and heterogeneous group of degenerative diseases caused by mutations in various genes. Given the favorable anatomical and immunological characteristics of the eye, gene therapy holds great potential for thei ...

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