Single Live Cell Monitoring of Protein Turnover Reveals Intercellular Variability and Cell-Cycle Dependence of Degradation Rates

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Proteins are foundational biomolecules of life playing a crucial role in a myriad of biological processes. Their function often requires interplay with other biomolecules, including proteins themselves. Protein-protein interactions (PPIs) are essential for ...

The cellular protein levels are determined by protein synthesis and turnover rates. Two processes are involved in the proteome's turnover in proliferating cells: protein degradation and dilution. In theory, maintaining the cellular proteome concentration, ...

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 ...

Aging is characterized by a decline in tissue function, but the underlying changes at cellular resolution across the organism remain unclear. Here, we present the Aging Fly Cell Atlas, a single-nucleus transcriptomic map of the whole aging Drosophila. We c ...

Chlorinated compounds are ubiquitous. However, accumulation of chlorine-containing waste has a negative impact on human health and the environment due to the inapplicability of common disposal methods, such as landfill and incineration. Here we report a su ...

Cis-genetic effects are key determinants of transcriptional divergence in discrete tissues and cell types. However, how cis- and trans-effects act across continuous trajectories of cellular differentiation in vivo is poorly understood. Here, we quantify al ...

Scaffold-based protein libraries are designed to be both diverse and rich in functional/folded proteins. However, introducing an extended diversity while preserving stability of the initial scaffold remains a challenge. Here we developed an original approa ...

High-throughput transcriptomics is of increasing fundamental biological and clinical interest. The generation of molecular data from large collections of samples, such as biobanks and drug libraries, is boosting the development of new biomarkers and treatm ...

Herein, we report a novel strategy for the modification of peptides based on the introduction of highly reactive hypervalent iodine reagents-ethynylbenziodoxolones (EBXs)-onto peptides. These peptide-EBXs can be readily accessed, by both solution- and soli ...

Proteins control nearly every facet of life on a molecular level. Proteins are formed from linear strings of amino acids, which fold into three-dimensional structures that can enact functions. Evolution has created highly efficient proteins in diverse fold ...

Rhodamines have been continuously optimized in brightness, biocompatibility, and color to fulfill the demands of modern bioimaging. However, the problem of phototoxicity caused by the excited fluorophore under long-term illumination has been largely neglec ...

De novo protein design enhances our understanding of the principles that govern protein folding and interactions, and has the potential to revolutionize biotechnology through the engineering of novel protein functionalities. Despite recent progress in comp ...

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 ...

Background: Transposable elements (TEs) have colonized the genomes of most metazoans, and many TE-embedded sequences function as cis-regulatory elements (CREs) for genes involved in a wide range of biological processes from early embryo- genesis to innate ...

Through site-specific generation of intermediary reactive aldehydes, Horner-Wadsworth-Emmons olefination can now deliver selective functionalization of stable recombinant proteins and monoclonal antibodies, whilst preserving protein integrity. ...

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 ...

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 ...

Over the past two decades, protein S-acylation (often referred to as S-palmitoylation) has emerged as an important regulator of vital signalling pathways. S-Acylation is a reversible post-translational modification that involves the attachment of a fatty a ...

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 ...

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 ...

Single Live Cell Monitoring of Protein Turnover Reveals Intercellular Variability and Cell-Cycle Dependence of Degradation Rates

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Engineering novel protein interactions with therapeutic potential using deep learning-guided surface design

Coordination of protein synthesis and degradation in mammalian cells

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

Aging Fly Cell Atlas identifies exhaustive aging features at cellular resolution

Tandem catalysis enables chlorine-containing waste as chlorination reagents

The dynamic genetic determinants of increased transcriptional divergence in spermatids

Design of an artificial phage-display library based on a new scaffold improved for average stability of the randomized proteins

Multi-well plate lid for single-step pooling of 96 samples for high-throughput barcode-based sequencing

Peptide-Hypervalent Iodine Reagent Chimeras: Enabling Peptide Functionalization and Macrocyclization

De novo designed proteins: a study in engineering novel folds and functions

Gentle Rhodamines for Live-Cell Fluorescence Microscopy

De novo protein design by inversion of the AlphaFold structure prediction network

Opportunities and challenges in design and optimization of protein function

Statistical learning quantifies transposable element-mediated cis-regulation

Horner-Wadsworth-Emmons olefination for bioconjugation

Predicting protein interactions using geometric deep learning on protein surfaces

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

Mechanisms and functions of protein S-acylation

Chromatin modules and their implication in genomic organization and gene regulation

Microsecond Time-Resolved Cryo-Electron Microscopy