Switch-peptides as folding precursors in self-assembling peptides and amyloid fibrillogenesis

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The invention relates to methods for the preparation of method of preparation of Tau aggregates, including fibrils, fibrillar species, soluble and insoluble oligomeric species, new Tau aggregates and uses thereof. The invention further relates to the uses ...

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 ...

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 ...

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 ...

Cartilage homeostasis, crucial for musculoskeletal function, is orchestrated by interconnected biophysical cues. In healthy cartilage, repetitive compressive loading not only elicits a range of mechanical stimuli but also induces a gradual transient temper ...

As the fundamental machinery orchestrating cellular functions, proteins influence the state of every cell profoundly. As cells exhibit significant variations from one to another, analyzing the proteome on a single-cell level is imperative to unravel their ...

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 ...

Preventing the misfolding or aggregation of TDP-43 is the most actively pursued disease-modifying strategy to treat amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. In our work, we provide proof of concept that native state stabili ...

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, ...

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 ...

Cupredoxins are widely occurring copper-binding proteins with a typical Greek-key beta barrel fold. They are generally described as electron carriers that rely on a T1 copper centre coordinated by four ligands provided by the folded polypeptide. The discov ...

The combination of palladium salts and bipyridyl ligands can lead to the formation of a large variety of coordination complexes, with different shapes and sizes, displaying a very versatile host-guest chemistry. Increasing their structural complexity remai ...

Macrocycles provide an attractive modality for drug development but the identification of ligands to targets of interest is hindered by the lack of large macrocyclic compound libraries for high-throughput screening. A strategy to efficiently synthesize lar ...

The synthesis of complex sugars is a key aspect of microbial biology. Cyclic beta-1,2-glucan (C beta G) is a circular polysaccharide critical for host interactions of many bacteria, including major pathogens of humans (Brucella) and plants (Agrobacterium). ...

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 ...

TAR DNA-binding protein with 43 kD (TDP-43) is a partially disordered protein that misfolds and accumulates in the brains of patients affected by several neurodegenerative diseases. TDP-43 oligomers have been reported to form due to aberrant misfolding or ...

This thesis consists of four Chapters unified by a singular theme â how do we develop disease models that faithfully reproduce the pathology seen in patients suffering from neurodegenerative disorders associated with the Tau protein, such as Alzheimerâ ...

Engineering protein biosensors that sensitively respond to specific biomolecules by triggering precise cellular responses is a major goal of diagnostics and synthetic cell biology. Previous biosensor designs have largely relied on binding structurally well ...

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 ...

Protein-protein interactions (PPIs) are responsible for regulating many biological processes in human bodies. PPIs often have a large binding site and often interact through an alpha helical segment. Therefore, the inhibition of PPIs can be difficult using ...

Switch-peptides as folding precursors in self-assembling peptides and amyloid fibrillogenesis

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Method of preparation of amyloidogenic protein aggregates and uses thereof

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

Microsecond Time-Resolved Cryo-Electron Microscopy

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

Synergetic Support of Cartilage Homeostasis via Coupled Thermal-Hydrostatic Pressure Stimuli

Development of tools and methods for protein identification: From single molecules to in vivo applications

Opportunities and challenges in design and optimization of protein function

Targeting TDP-43 Proteinopathies in Neurodegeneration by its Native-State Stabilization

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

Predicting protein interactions using geometric deep learning on protein surfaces

Beyond the coupled distortion model: structural analysis of the single domain cupredoxin AcoP, a green mononuclear copper centre with original features

Palladium-based supramolecular assemblies: from complex structures to water-soluble anion-receptors

Methods for high-throughput synthesis and screening of peptide libraries

Structure-function analysis of the cyclic β-1,2-glucan synthase from Agrobacterium tumefaciens

Mechanisms and functions of protein S-acylation

Recombinant Full-Length TDP-43 Oligomers Retain Their Ability to Bind RNAs, Are Not Toxic, and Do Not Seed TDP-43 Aggregation in Vitro

Deconstructing and Reconstructing the Complexity of Tau pathology

Computational design of dynamic receptor—peptide signaling complexes applied to chemotaxis

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

Synthesis and application of bifunctional hypervalent iodine reagents for peptide modification