A5026933180- RNA and protein synthesis mechanisms
- Protein Structure and Dynamics
- Genomics and Rare Diseases
- Genomics and Phylogenetic Studies
- Cellular transport and secretion
- CRISPR and Genetic Engineering
- Gene expression and cancer classification
- Enzyme Structure and Function
- Glycosylation and Glycoproteins Research
- Genomics and Chromatin Dynamics
- Single-cell and spatial transcriptomics
- Ubiquitin and proteasome pathways
- Cell Image Analysis Techniques
- Endoplasmic Reticulum Stress and Disease
- Heat shock proteins research
- Bacterial biofilms and quorum sensing
- Monoclonal and Polyclonal Antibodies Research
- Microbial Natural Products and Biosynthesis
- Protein Degradation and Inhibitors
- Receptor Mechanisms and Signaling
- Developmental Biology and Gene Regulation
- Bacterial Genetics and Biotechnology
- Hedgehog Signaling Pathway Studies
- Congenital limb and hand anomalies
- Advanced Proteomics Techniques and Applications
KU Leuven
2020-2025
VIB-KU Leuven Center for Brain & Disease Research
2019-2025
Switch
2024
Single-cell technologies allow measuring chromatin accessibility and gene expression in each cell, but jointly utilizing both layers to map bona fide regulatory networks enhancers remains challenging. Here, we generate independent single-cell RNA-seq ATAC-seq atlases of the Drosophila eye-antennal disc spatially integrate data into a virtual latent space that mimics organization 2D tissue using ScoMAP (Single-Cell Omics Mapping spatial Axes Pseudotime ordering). To validate predicted...
The tendency for proteins to form aggregates is an inherent part of every proteome and arises from the self-assembly short protein segments called aggregation-prone regions (APRs). While posttranslational modifications (PTMs) have been implicated in modulating aggregation, their direct role APRs remains poorly understood. In this study, we used a combination proteome-wide computational analyses biophysical techniques investigate potential involvement PTMs aggregation regulation. Our findings...
Drug-resistant bacteria pose an urgent global health threat, necessitating the development of antibacterial compounds with novel modes action. Protein biosynthesis accounts for up to half energy expenditure bacterial cells, and consequently inhibiting efficiency or fidelity ribosome is a major target existing antibiotics. Here, we describe alternative mode action that affects same process: allowing translation proceed but causing co-translational aggregation nascent peptidic chain. We show...
Highlights•Mutations in the globular and amyloid state are thermodynamically correlated•The genetic code tightens this relationship between native state•Strongly amyloidogenic sequences proteins deeply conserved•Positive selection of propensity will favor protein stabilitySummaryThe amyloid-like aggregation present most is generally considered to be a secondary side effect resulting from requirements stability. Here, we demonstrate, however, that mutations correlated rather than simply...
Abstract Structural bioinformatics suffers from the lack of interfaces connecting biological structures and machine learning methods, making application modern neural network architectures impractical. This negatively affects development structure-based causing a bottleneck in research. Here we present PyUUL ( https://pyuul.readthedocs.io/ ), library to translate into 3D tensors, allowing an out-of-the-box state-of-the-art deep algorithms. The converts macromolecules data typical computer...
Because of vectorial protein translation, residues that interact in the native structure but are distantly separated primary sequence unavailable simultaneously. Instead, there is a temporal delay during which N-terminal interaction partner unsatisfied and potentially vulnerable to non-native interactions. We introduce "Native Fold Delay" (NFD), metric integrates topology with translation kinetics quantify such delays. found many proteins exhibit NFDs range tens seconds. These residues,...
Amyloid fibrils adopt diverse structural polymorphs that underlie disease-specific phenotypes, but the thermodynamic principles guiding their formation and maturation remain poorly understood. Here, we apply energetic profiling to time series from cryo-EM datasets of IAPP, tau, α-synuclein decode governing fibril maturation, stability polymorphic divergence. By mapping residue-level free energy contributions across experimentally resolved assembly pathways, reconstruct complex trajectories...
Mutant KRAS is a major driver of oncogenesis in multitude cancers but remains challenging target for classical small molecule drugs, motivating the exploration alternative approaches. Here, we show that aggregation-prone regions (APRs) primary sequence oncoprotein constitute intrinsic vulnerabilities can be exploited to misfold into protein aggregates. Conveniently, this propensity present wild-type increased common oncogenic mutations at positions 12 and 13. We synthetic peptides...
There is an arms race between beta-lactam antibiotics development and co-evolving beta-lactamases, which provide resistance by breaking down rings. We have observed that certain beta-lactamases tend to aggregate, persists throughout their evolution under the selective pressure of on active sites. Interestingly, we find existing beta-lactamase site inhibitors can act as molecular chaperones, promoting proper folding these factors. Therefore, created Pept-Ins, synthetic peptides designed...
Abstract Circumferential skin creases (CSC-KT) is a rare polymalformative syndrome characterised by intellectual disability associated with on the limbs, and very characteristic craniofacial malformations. Previously, heterozygous homozygous mutations in MAPRE2 were found to be causal for this disease. encodes member of evolutionary conserved microtubule plus end tracking proteins, binding (EB) family. Unlike MAPRE1 MAPRE3, not required persistent growth stabilization microtubules, but plays...
Abstract Single-cell technologies allow measuring chromatin accessibility and gene expression in each cell, but jointly utilizing both layers to map bona fide regulatory networks enhancers remains challenging. Here, we generate independent single-cell RNA-seq ATAC-seq atlases of the Drosophila eye-antennal disc spatially integrate data using a virtual latent space that mimics organization 2D tissue. To validate predicted enhancers, use large collection enhancer-reporter lines identify ∼85%...
Next-generation sequencing technologies yield large numbers of genetic alterations, which a subset are missense variants that alter an amino acid in the protein product. These can have potentially destabilizing effect leading to increased risk misfolding and aggregation. Multiple software tools exist predict single-nucleotide on proteins, however, pipeline integrating these while starting from NGS data output list is lacking.The previous version SNPeffect 4.0 (De Baets Nucleic Acids Res...
ABSTRACT The tendency for proteins to form aggregates is an inherent part of every proteome and arises from the self-assembly short protein segments called aggregation-prone regions (APRs). While post-translational modifications (PTMs) have been implicated in modulating aggregation, their direct role APRs remains poorly understood. In this study, we used a combination proteome-wide computational analyses biochemical techniques investigate potential involvement PTMs aggregation regulation....
Because of vectorial protein production, residues that interact in the native structure but are distantly separated primary sequence unavailable simultaneously. Instead, there is a temporal delay during which N-terminal interaction partner vulnerable to off-pathway, non-native interactions. In this analysis, we introduce "FoldDelay" (FD), metric integrates topological pattern atomic interactions with translation kinetics quantify such time delays. The FD reveals many proteins, particularly...