An ancestral regulatory mechanism underlies Hoxd gene expression in both developing genitals and digits

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Bacterial diversity dominates variable macrophage responses of tuberculosis patients in Tanzania

Jacques Fellay, Zhi Ming Xu

The Mycobacterium tuberculosis complex (MTBC) comprises nine human-adapted lineages that differ in their geographical distribution. Local adaptation of specific MTBC genotypes to the respective human host population has been invoked in this context. We aim ...

Nature Portfolio2024

Resolving bacterial cell biology: from replisome dynamics to cell wall synthesis

Chen Zhang

Bacteria are ubiquitous single cellular organisms. Compared to eukaryotic cells, bacteria have two unique characteristics: the membrane-less nucleoid and the cell wall built of peptidoglycan (PG). In most bacteria, a single circular chromosome is compacted ...

EPFL2024

Microsecond Time-Resolved Cryo-Electron Microscopy

Oliver Florian Harder

Recently, single-particle cryo-electron microscopy emerged as a technique capable of determining protein structures at near-atomic resolution and resolving protein dynamics with a temporal resolution ranging from second to milliseconds. This thesis describ ...

EPFL2024

Investigating the intra-molecular and inter-molecular effects of post-translational modifications on intrinsically disordered protein regions and structured protein regions

Zhidian Zhang

Post-translational modifications (PTMs) play a pivotal role in regulating protein structure, interaction, and function. Aberrant PTM patterns are associated with diseases. Moreover, individual PTMs have a complex interaction with each other, known as PTM c ...

EPFL2024

Deciphering the molecular events leading to the global restoration of the chromatin landscape during mitotic exit

Silja Michelle Placzek

Two fundamental properties of embryonic stem cells (ESCs) are their ability to self-renew and differentiate into all somatic cell types. Maintenance of their identity faces major challenges when transitioning through mitosis, as most DNA-binding proteins a ...

EPFL2023

Chromatin modules and their implication in genomic organization and gene regulation

Judith Franziska Kribelbauer, Bart Deplancke, Guido Van Mierlo

Regulation of gene expression is a complex but highly guided process. While genomic technologies and computational approaches have allowed high-throughput mapping of cis-regulatory elements (CREs) and their interactions in 3D, their precise role in regulat ...

ELSEVIER SCIENCE LONDON2023

Sequential and directional insulation by conserved CTCF sites underlies the Hox timer in stembryos

Denis Duboule, Lucille Delisle, Alexandre Gauthier Aurèle Mayran, Hocine Rekaik, Célia Corinne Renée Bochaton

Temporal activation of Hox genes in mouse pseudo-embryos in vitro initiates at the anterior part of the cluster and is accompanied by asymmetric loading of cohesin. Posterior CTCF sites then successively act as transient insulators, regulating the timed tr ...

NATURE PORTFOLIO2023

cgNA+: A sequence-dependent coarse-grain model of double-stranded nucleic acids

Rahul Sharma

DNA mechanics plays a crucial role in many biological processes, including nucleosome positioning and protein-DNA interactions. It is believed that nature employs epigenetic modifications in DNA to further regulate gene expression. Moreover, double-strande ...

EPFL2023

Impact of phylogeny on structural contact inference from protein sequence data

Anne-Florence Raphaëlle Bitbol, Umberto Lupo, Nicola Dietler

Local and global inference methods have been developed to infer structural contacts from multiple sequence alignments of homologous proteins. They rely on correlations in amino acid usage at contacting sites. Because homologous proteins share a common ance ...

ROYAL SOC2023

Environment-dependent epistasis increases phenotypic diversity in gene regulatory networks

Florence Gauye, Florian Baier

Mutations to gene regulatory networks can be maladaptive or a source of evolutionary novelty. Epistasis con-founds our understanding of how mutations affect the expression patterns of gene regulatory networks, a chal-lenge exacerbated by the dependence of ...

AMER ASSOC ADVANCEMENT SCIENCE2023

Cis-regulatory effect of HPV integration is constrained by host chromatin architecture in cervical cancers

Daniele Tavernari

Human papillomavirus (HPV) infections are the primary drivers of cervical cancers, and often HPV DNA gets integrated into the host genome. Although the oncogenic impact of HPV encoded genes is relatively well known, the cis-regulatory effect of integrated ...

Wiley2023

Exploring the role of transcriptional and post-transcriptional processes in mRNA co-expression

Benjamin Joao Clément Antonin Hadrien Martin

Co-expression of two or more genes at the single-cell level is usually associated with functional co-regulation. While mRNA co-expression-measured as the correlation in mRNA levels-can be influenced by both transcriptional and post-transcriptional events, ...

Wiley2023