"Switch peptides" : conception et synthèse d'inhibiteurs ou destructeurs potentiels de fibrilles amyloïdes

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The preclinical phase of Alzheimer’s disease represents a crucial time window for therapeutic intervention but requires the identification of clinically relevant biomarkers that are sensitive to the effects of disease-modifying drugs. Amyloid peptide and t ...

Alpha-synuclein (aSyn) post-translational modifications (PTM), especially phosphorylation at serine 129 and C-terminal truncations, are highly enriched in Lewy bodies (LB), Lewy neurites, and other pathological aggregates in Parkinson's disease and synucle ...

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 ...

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, ...

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 ...

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 ...

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 ...

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 ...

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 ...

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 ...

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 ...

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 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). ...

Transmembrane protein 16 F (TMEM16F) is a Ca2+-activated homodimer which functions as an ion channel and a phospholipid scramblase. Despite the availability of several TMEM16F cryogenic electron microscopy (cryo-EM) structures, the mechanism of activation ...

Metal-organic frameworks (MOFs) are a rapidly growing class of materials that offer great promise in various applications. However, the synthesis remains challenging: for example, a range of crystal structures can often be accessed from the same building b ...

An organic dye photocatalyzed lactonization-alkynylation of easily accessible homoallylic cesium oxalates using ethynylbenziodoxolone (EBX) reagents has been developed. The reaction gave access to valuable functionalized lactones and lactams in up to 88% y ...

Living photovoltaics are microbial electrochemical devices that use whole cell–electrode interactions to convert solar energy to electricity. The bottleneck in these technologies is the limited electron transfer between the microbe and the electrode surfac ...

The invention of 3D atomic force microscopy (3D-AFM) has enabled visualizing subnanoscale 3D hydration structures. Meanwhile, its applications to imaging flexible molecular chains have started to be experimentally explored. However, the validity and princi ...

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 ...

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 ...

"Switch peptides" : conception et synthèse d'inhibiteurs ou destructeurs potentiels de fibrilles amyloïdes

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Can brain network connectivity facilitate the clinical development of disease-modifying anti-Alzheimer drugs?

Differential role of C-terminal truncations on alpha-synuclein pathology and Lewy body formation

Microsecond Time-Resolved Cryo-Electron Microscopy

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

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

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

Methods for high-throughput synthesis and screening of peptide libraries

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

Predicting protein interactions using geometric deep learning on protein surfaces

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

Opportunities and challenges in design and optimization of protein function

Method of preparation of amyloidogenic protein aggregates and uses thereof

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

Structural heterogeneity of the ion and lipid channel TMEM16F

How Reproducible is the Synthesis of Zr-Porphyrin Metal-Organic Frameworks? An Interlaboratory Study

Organic Dye Photocatalyzed Synthesis of Functionalized Lactones and Lactams via a Cyclization-Alkynylation Cascade

Polydopamine-coated photoautotrophic bacteria for improving extracellular electron transfer in living photovoltaics

Revealing the Mechanism Underlying 3D-AFM Imaging of Suspended Structures by Experiments and Simulations

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

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