Publications related to Switch peptides : in situ nucleation of conformational transitions relevant to protein misfolding diseases

Microsecond Time-Resolved Cryo-Electron Microscopy

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

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

Mahdi Hijazi

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 ...

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

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

Felix Naef, Pierre Vandergheynst, Cédric Gobet, Mohan Vamsi Nallapareddy, Francesco Craighero

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, ...

PMLR2024

Opportunities and challenges in design and optimization of protein function

Bruno Emanuel Ferreira De Sousa Correia, Casper Alexander Goverde

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 ...

Nature Portfolio2024

Predicting protein interactions using geometric deep learning on protein surfaces

Freyr Sverrisson

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 ...

EPFL2024

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

Lixin Yang

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 ...

EPFL2024

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

Salome Riccarda Püntener

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 ...

EPFL2024

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

Marcos Penedo Garcia

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 ...

Wiley-V C H Verlag Gmbh2024

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

Yanheng Guo

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 ...

EPFL2024

Controlled Formation of Nanoribbons and Their Heterostructures via Assembly of Mass-Selected Inorganic Ions

Klaus Kern

Control of nanomaterial dimensions with atomic precision through synthetic methods is essential to understanding and engineering of nanomaterials. For single-layer inorganic materials, size and shape controls have been achieved by self-assembly and surface ...

Wiley-V C H Verlag Gmbh2024

Method of preparation of amyloidogenic protein aggregates and uses thereof

Hilal Lashuel, Galina Limorenko

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 ...

2024

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

Henning Paul-Julius Stahlberg, Dongchun Ni

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). ...

Nature Portfolio2024

Structural heterogeneity of the ion and lipid channel TMEM16F

Horst Vogel

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 ...

Nature Portfolio2024

Ion Spectroscopy Reveals Structural Difference for Proteins Microhydrated by Retention and Condensation of Water

Oleg Boyarkine, Andrei Zviagin

Protein ubiquitin in its +7 charge state microhydrated by 5 and 10 water molecules has been interrogated in the gas phase by cold ion UV/IR spectroscopy. The complexes were formed either by condensing water onto the unfolded bare proteins in a temperature- ...

Amer Chemical Soc2024

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

Fabian Fischer, Ardemis Anoush Boghossian, Charlotte Elisabeth Marie Roullier, Melania Reggente, Mohammed Mouhib, Patricia Brandl, Hanxuan Wang

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 ...

2024

Multimodal transcriptomic atlases of mouse spinal cord injury

Matthieu Pierre Gautier

A spinal cord injury (SCI) triggers a cascade of molecular and cellular responses involving inflammatory cell infiltration and cytokine release, apoptosis, demyelination, excitotoxicity, ischemia, and the formation of a fibrotic scar surrounded by an astro ...

EPFL2024

When Subtyping Constraints Liberate A Novel Type Inference Approach for First-Class Polymorphism

Lionel Emile Vincent Parreaux, Aleksander Slawomir Boruch-Gruszecki

Type inference in the presence of first-class or "impredicative" second-order polymorphism a la System F has been an active research area for several decades, with original works dating back to the end of the 80s. Yet, until now many basic problems remain ...

Assoc Computing Machinery2024

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

Anthony Marchand

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 ...

EPFL2024

Mechanisms and functions of protein S-acylation

Françoise Gisou van der Goot Grunberg, Laurence Gouzi Abrami, Francisco De Magalhães Sarmento R De Mesquita

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 ...

Nature Portfolio2024