CREB and ChREBP oppositely regulate SIRT1 expression in response to energy availability

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Background & Aims: Current therapies for the treatment of alcohol-related liver disease (ALD) have proven largely ineffective. Patients relapse and the disease progresses even after liver transplantation. Altered epigenetic mechanisms are characteristic of ...

Translation elongation plays an important role in regulating protein concentrations in the cell, and dysregulation of this process has been linked to several human diseases. In this study, we use data from ribo-seq experiments to model ribosome densities, ...

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 ...

The phenomenon of allostery, a general property in proteins that has been heralded as "the second secret of life" remains elusive to our understanding and even more challenging to incorporate into protein design. One example of allosteric proteins with gre ...

In the domain of computational structural biology, predicting protein interactions based on molecular structure remains a pivotal challenge. This thesis delves into this challenge through a series of interconnected studies. The first chapter introduces th ...

Since Strahl and Allis proposed the "language of covalent histone modifications", a host of experimental studies have shed light on the different facets of chromatin regulation by epigenetic mechanisms. Initially proposed as a concept for controlling gene ...

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 ...

Adipose tissues serve as an energy reservoir and endocrine organ, yet the mechanisms that coordinate these functions remain elusive. Here, we show that the transcriptional coregulators, YAP and TAZ, uncouple fat mass from leptin levels and regulate adipocy ...

In oxidative phosphorylation, respiratory complex I serves as an entry point in the electron transport chain for electrons generated in catabolic processes in the form of NADH. An ancestral version of the complex, lacking the NADH-oxidising module, is enco ...

Redox homeostasis is a key factor in maintaining cellular function and health. The main determinant of the intracellular redox potential is ubiquitous glutathione (GSH) together with its oxidized dimer (GSSG). Importantly, both redox equilibrium and GSH ho ...

Constitutive heterochromatin is essential for transcriptional silencing and genome integrity. The establishment of constitutive heterochromatin in early embryos and its role in early fruitfly development are unknown. Lysine 9 trimethylation of histone H3 ( ...

The field of protein design has made remarkable progress over the past decade. Historically, the low reliability of purely structure-based design methods limited their application, but recent strategies that combine structure-based and sequence-based calcu ...

SARS-CoV-2 infection requires Spike protein-mediated fusion between the viral and cellular membranes. The fusogenic activity of Spike depends on its post-translational lipid modification by host S-acyltransferases, predominantly ZDHHC20. Previous observati ...

Telomeres are the nucleoprotein structures at the ends of linear chromosomes. Telomeres are transcribed into long non-coding Telomeric Repeat-Containing RNA (TERRA), whose functions rely on its ability to associate with telomeric chromatin. The conserved T ...

The rapid progress in the field of deep learning has had a significant impact on protein design. Deep learning methods have recently produced a breakthrough in protein structure prediction, leading to the availability of high-quality models for millions of ...

Proteins, the central building blocks of life, play pivotal roles in nearly every biological function. To do so, these macromolecular structures interact with their surrounding environment in complex ways, leading to diverse functional behaviors. The predi ...

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 ...

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 ...

Computational models starting from large ensembles of evolutionarily related protein sequences capture a representation of protein families and learn constraints associated to protein structure and function. They thus open the possibility for generating no ...

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, ...

CREB and ChREBP oppositely regulate SIRT1 expression in response to energy availability

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Anti-miR-873-5p improves alcohol-related liver disease by enhancing hepatic deacetylation via SIRT1

Towards improving full-length ribosome density prediction by bridging sequence and graph-based representations

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

From Sequence to Dynamics to Function: Computational Design of Allostery and Ligand Selectivity in G-Protein Coupled Receptors

Predicting protein interactions using geometric deep learning on protein surfaces

Decoding Chromatin Ubiquitylation: A Chemical Biology Perspective

Microsecond Time-Resolved Cryo-Electron Microscopy

Hippo-YAP/TAZ signalling coordinates adipose plasticity and energy balance by uncoupling leptin expression from fat mass

Conditional essentiality of the 11-subunit complex I-like enzyme in strict anaerobes: the case of Desulfitobacterium hafniense strain DCB-2

HaloTag-Based Tools for Live-Cell Imaging and Elucidation of Organellar Redox Biology

Inheritance of H3K9 methylation regulates genome architecture in Drosophila early embryos

Opportunities and challenges in design and optimization of protein function

SARS-CoV-2 hijacks a cell damage response, which induces transcription of a more efficient Spike S-acyltransferase

The THO complex counteracts TERRA R-loop-mediated telomere fragility in telomerase(+) cells and telomeric recombination in ALT(+) cells

A new age in protein design empowered by deep learning

A Geometric Transformer for Structural Biology: Development and Applications of the Protein Structure Transformer

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

Chromatin modules and their implication in genomic organization and gene regulation

Generative power of a protein language model trained on multiple sequence alignments

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