A5039155418- Protein Structure and Dynamics
- Bioinformatics and Genomic Networks
- Enzyme Structure and Function
- Alzheimer's disease research and treatments
- Monoclonal and Polyclonal Antibodies Research
- Genomics and Rare Diseases
- Cancer-related Molecular Pathways
- Computational Drug Discovery Methods
- Amyotrophic Lateral Sclerosis Research
- Protein purification and stability
- Ubiquitin and proteasome pathways
- Advanced Proteomics Techniques and Applications
- Protein Kinase Regulation and GTPase Signaling
- Pediatric health and respiratory diseases
- Asthma and respiratory diseases
- Cancer Research and Treatments
- Bacteriophages and microbial interactions
- Peptidase Inhibition and Analysis
- Oral and gingival health research
- Fractal and DNA sequence analysis
- 14-3-3 protein interactions
- Cell death mechanisms and regulation
- Neurological diseases and metabolism
- Biosimilars and Bioanalytical Methods
- Prion Diseases and Protein Misfolding
AstraZeneca (United Kingdom)
2021-2025
KU Leuven
2012-2023
VIB-KU Leuven Center for Brain & Disease Research
2011-2023
University of Twente
2019
MRC Laboratory of Molecular Biology
2017-2018
Vlaams Instituut voor Biotechnologie
2012-2016
Vrije Universiteit Brussel
2011-2015
University of Antwerp
2015
ZNA Middelheim Hospital
2015
University Medical Center Groningen
2015
Abstract Hexanucleotide repeat expansions in C9orf72 are the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD) (c9ALS/FTD). Unconventional translation these repeats produces dipeptide proteins (DPRs) that may neurodegeneration. We performed a modifier screen Drosophila discovered critical role for importins exportins, Ran-GTP cycle regulators, nuclear pore components arginine methylases mediating DPR toxicity. These findings provide evidence an...
Single nucleotide variants (SNVs) are, together with copy number variation, the primary source of variation in human genome and are associated phenotypic such as altered response to drug treatment susceptibility disease. Linking structural effects non-synonymous SNVs functional outcomes is a major issue bioinformatics. The SNPeffect database (http://snpeffect.switchlab.org) uses sequence- structure-based bioinformatics tools predict effect protein-coding on phenotype proteins. It integrates...
Article14 May 2018Open Access Transparent process High-throughput discovery of functional disordered regions: investigation transactivation domains Charles NJ Ravarani Corresponding Author [email protected] orcid.org/0000-0003-0952-3396 MRC Laboratory Molecular Biology, Cambridge, UK Search for more papers by this author Tamara Y Erkina Butler University, Indianapolis, IN, USA Greet De Baets Daniel C Dudman Alexandre M Erkine orcid.org/0000-0002-1880-4854 Madan Babu...
<h3>Objective:</h3> To assess the genetic contribution of <i>TBK1</i>, a gene implicated in amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and FTD-ALS, Belgian FTD ALS patient cohorts containing significant part genetically unresolved patients. <h3>Methods:</h3> We sequenced <i>TBK1</i> hospital-based cohort 482 unrelated patients with FTD-ALS 147 an extended family DR158. followed up mutation carriers by segregation studies, transcript protein expression analysis,...
Soluble functional proteins may transform into insoluble amyloid fibrils that deposit in a variety of tissues. Amyloid formation is hallmark age-related degenerative disorders. Perhaps surprisingly, can also be beneficial and are frequently exploited for diverse roles organisms. Here we introduce AmyPro, an open-access database providing comprehensive, carefully curated collection validated fibril-forming from all kingdoms life classified broad categories (http://amypro.net). In particular,...
Abstract Natural selection shapes protein solubility to physiological requirements and recombinant applications that require higher concentrations are often problematic. This raises the question whether of natural sequences can be improved. We here show an anti-correlation between number aggregation prone regions (APRs) in a sequence its solubility, suggesting mutational suppression APRs provides simple strategy increase solubility. mutations at specific positions within structure act as APR...
Abstract Although p53 protein aggregates have been observed in cancer cell lines and tumour tissue, their impact remains largely unknown. Here, we extensively screened for aggregation phenotypes biopsies, identified nuclear inclusion bodies ( nIBs ) of transcriptionally inactive mutant or wild‐type as the most frequent aggregation‐like phenotype across six different types. p53‐positive co‐stained with markers, shared molecular hallmarks commonly found neurodegenerative disorders. In culture,...
Protein aggregation is a major factor limiting the biotechnological and therapeutic application of many proteins, including enzymes monoclonal antibodies. The molecular principles underlying are by now sufficiently understood to allow rational redesign natural polypeptide sequences for decreased tendency, hence potentially increased expression solubility. Given that aggregation-prone regions (APRs) tend contribute stability hydrophobic core or functional sites protein, mutations in these...
Amyloid beta and bind by filter binding (View Interaction: 1, 2, 3)
Protein aggregation is a hallmark of over 30 human pathologies. In these diseases, the one or few specific proteins often toxic, leading to cellular degeneration and/or organ disruption in addition loss-of-function resulting from protein misfolding. Although pathophysiological consequences diseases are overt, molecular dysregulations aggregate toxicity still unclear and appear be diverse multifactorial. The mechanisms therefore biophysical parameters favoring better understood. Here we...
Emerging evidence suggested a converging mechanism in neurodegenerative brain diseases (NBD) involving early neuronal network dysfunctions and alterations the homeostasis of firing as culprits neurodegeneration. In this study, we used paired-end short-read direct long-read whole genome sequencing to investigate an unresolved autosomal dominant dementia family significantly linked 7q36. We identified validated chromosomal inversion ca. 4 Mb, segregating on disease haplotype disrupting coding...
Abstract Background Single-cell technologies enable the fine mapping of disease and treatment mechanisms in inflammatory bowel (IBD). We sought to leverage these insights discover novel drug targets with precise therapeutic hypotheses. To this end, we previously constructed one largest integrated single-cell atlas IBD patient-derived tissue samples1. then used Immunai’s ImmunoDynamics EngineTM, a proprietary machine learning (ML) framework, identify transcriptional signatures inflammation...
We previously showed the existence of selective pressure against protein aggregation by enrichment aggregation-opposing 'gatekeeper' residues at strategic places along sequence proteins. Here we analyzed relationship between lifetime and combining experimentally determined turnover rates, expression data, structural data chaperone interaction on a set more than 500 find that sequences is not homogeneous but short-living proteins average have higher propensity fewer interactions long-living...
Abstract Motivation: Protein aggregation is associated with a number of protein misfolding diseases and major concern for therapeutic proteins. Aggregation caused by the presence aggregation-prone regions (APRs) in amino acid sequence protein. The lower propensity APRs better they are protected native interactions within folded structure protein, more prevented. Therefore, both local thermodynamic stability their intrinsic key parameter that needs to be optimized prevent aggregation....
Accurate prediction of the impact genomic variation on phenotype is a major goal computational biology and an important contributor to personalized medicine. Computational predictions can lead better understanding mechanisms underlying genetic diseases, including cancer, but their adoption requires thorough unbiased assessment. Cystathionine-beta-synthase (CBS) enzyme that catalyzes first step transsulfuration pathway, from homocysteine cystathionine, in which variations are associated with...
Abstract The accumulation of toxic protein aggregates is thought to play a key role in range degenerative pathologies, but it remains unclear why aggregation polypeptides into non-native assemblies and cellular clearance pathways offer ineffective protection. We here study the A4V mutant SOD1, which forms motor neurons patients with familial amyotrophic lateral sclerosis (ALS). A comparison location prone regions (APRs) Hsp70 binding sites denatured state SOD1 reveals that ALS-associated...