A5077060970- Ubiquitin and proteasome pathways
- Protein Structure and Dynamics
- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- RNA and protein synthesis mechanisms
- Enzyme Structure and Function
- Hippo pathway signaling and YAP/TAZ
- Chemical Synthesis and Analysis
- Cancer-related Molecular Pathways
- Computational Drug Discovery Methods
- Peptidase Inhibition and Analysis
- Bioinformatics and Genomic Networks
- Autophagy in Disease and Therapy
- vaccines and immunoinformatics approaches
- Protein purification and stability
- SARS-CoV-2 and COVID-19 Research
- Machine Learning in Bioinformatics
- Magnetic and Electromagnetic Effects
- Geomagnetism and Paleomagnetism Studies
- Geology and Paleoclimatology Research
- Plant biochemistry and biosynthesis
- Photosynthetic Processes and Mechanisms
- Genomics and Phylogenetic Studies
- Bacteriophages and microbial interactions
- Protein Degradation and Inhibitors
Icosagen (Estonia)
2023-2025
University of Waterloo
2022-2025
University of Toronto
2012-2022
Donnelly College
2019
Occupational Cancer Research Centre
2014-2018
Technische Universität Dresden
2006-2012
DNA repair is essential to maintain genome integrity, and genes with roles in are frequently mutated a variety of human diseases. Repair via homologous recombination typically restores the original sequence without introducing mutations, number that required for double-strand break (HR-DSBR) have been identified. However, systematic analysis this important pathway mammalian cells has not reported. Here, we describe genome-scale endoribonuclease-prepared short interfering RNA (esiRNA) screen...
Significance Although knowledge about the human interactome is increasing in coverage because of development high-throughput technologies, fundamental gaps remain. In particular, interactions mediated by short linear motifs are great importance for signaling, but systematic experimental approaches their detection missing. We fill this important gap developing a dedicated approach that combines bioinformatics, custom oligonucleotide arrays and peptide-phage display. computationally design...
We present an integrated approach that predicts and validates novel anti-cancer drug targets. first built a classifier integrates variety of genomic systematic datasets to prioritize targets specific for breast, pancreatic ovarian cancer. then devised strategies inhibit these selected set are amenable inhibition by small molecules, antibodies synthetic peptides. validated the predicted showing strong anti-proliferative effects both peptide molecule inhibitors against our
Advances in sequencing have led to a rapid accumulation of mutations, some which are associated with diseases. However, draw mechanistic conclusions, biochemical understanding these mutations is necessary. For coding accurate prediction significant changes either the stability proteins or their affinity binding partners required. Traditional methods used semi-empirical force fields, while newer employ machine learning sequence and structural features. Here, we show how combining both...
ELASPIC is a novel ensemble machine-learning approach that predicts the effects of mutations on protein folding and protein-protein interactions. Here, we present webserver, which makes pipeline available through fast intuitive interface. The webserver can be used to evaluate effect any in Uniprot database, allows all predicted results, including modeled wild-type mutated structures, managed viewed online downloaded if needed. It backed by database contains improved structural domain...
Glycosaminoglycans (GAGs) are anionic polysaccharides, which participate in key processes the extracellular matrix by interactions with protein targets. Due to their charged nature, accurate consideration of electrostatic and water-mediated is indispensable for understanding GAGs binding properties. However, solvent often overlooked molecular recognition studies. Here we analyze abundance GAG-protein interfaces investigate challenges adding explicit docking experiments. We observe PDB being...
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has made it clear that combating outbreaks benefits from a combination of vaccines and therapeutics. A promising drug target common to all coronaviruses—including SARS-CoV, MERS-CoV, SARS-CoV-2—is the papain-like protease (PLpro). PLpro cleaves part viral replicase polyproteins into non-structural protein subunits, which are essential replication cycle. Additionally, can cleave both ubiquitin ubiquitin-like ISG15 host...
Article8 December 2020Open Access Transparent process Large-scale survey and database of high affinity ligands for peptide recognition modules Joan Teyra orcid.org/0000-0003-2816-339X The Donnelly Centre, University Toronto, ON, CanadaThese authors contributed equally to this work Search more papers by author Abdellali Kelil orcid.org/0000-0002-0406-2052 Shobhit Jain Canada Department Computer Science, Mohamed Helmy Raghav Jajodia Indian Institute Engineering Science Technology, Shibpur,...
N-degron E3 ubiquitin ligases recognize specific residues at the N-termini of substrates. Although molecular details recognition are known for several ligases, range N-terminal motifs that can bind a given substrate binding domain remains unclear. Here, we discovered capacity Gid4 and Gid10 receptor subunits yeast "GID"/human "CTLH" multiprotein to tightly wide whose is determined in part by downstream sequence context. Screening phage displaying peptide libraries with exposed identified...
Abstract Background Currently there is a strong need for methods that help to obtain an accurate description of protein interfaces in order be able understand the principles govern molecular recognition and function. Many recent efforts computationally identify characterize networks extract interaction information at atomic resolution from PDB. However, they pay none or little attention small ligands solvent. They are key components mediators interactions fundamental complete interfaces....
Detailed information about protein interactions is critical for our understanding of the principles governing recognition mechanisms. The structures many proteins have been experimentally determined in complex with different ligands bound either same or binding regions. Thus, structural interactome requires development tools to classify A proper classification may provide a general view regions that uses bind others and also facilitate detailed comparative analysis interacting specific at...
RNA viruses have evolved numerous strategies to overcome host resistance and immunity, including the use of multifunctional proteases that not only cleave viral polyproteins during virus replication but also deubiquitinate cellular proteins suppress ubiquitin (Ub)-mediated antiviral mechanisms. Here, we report an approach attenuate infection Arabidopsis thaliana by Turnip Yellow Mosaic Virus (TYMV) suppressing polyprotein cleavage deubiquitination activities TYMV protease (PRO). Performing...
Background: ADORA2A (A2AR), is an adenosine receptor that suppresses immune cell toxicity through sensing extracellular adenosine. A2AR belongs to a group of seven-transmembrane proteins called G protein-coupled receptors (GPCRs) which act as detectors various signals from outside the cell. We aim reduce immunosuppressive properties in tumor microenvironment (TME) by targeting with monoclonal antibodies (mAbs). mAbs are attractive modality therapeutically target complex multi-pass membrane...
Abstract Chimeric antigen receptor (CAR) T cell therapies have achieved remarkable efficacy in treating B malignancies but shown limited clinical success patients with solid tumors. A key challenge advancing these lies the identification and targeting of highly tumor-specific antigens to ensure both safety efficacy. In this study, we employed HybriFree B-cell cloning technology phage display discover antibodies Claudin-6 (CLDN6), an oncofetal protein selectively expressed subsets ovarian,...
Abstract Background: Cancer cells often exhibit upregulated glucose metabolism to support their abnormal growth and division. Targeting the cancer-specific transporter GLUT-1 offers a promising strategy limit uptake disrupt tumor metabolism. Unlike small molecule inhibitors, monoclonal antibodies provide unique opportunity selectively target complex multi-pass membrane transporters. This study presents development of highly specific that recognize glycovariants, effectively blocking function...
Abstract Background: Claudin 6 (CLDN6), a tight junction protein, is an oncofetal antigen with limited expression in adult tissues but aberrantly overexpressed several cancers, including ovarian, testicular, and gastric tumors. Its tumor-specific critical role maintaining cell adhesion make CLDN6 compelling target for cancer therapy. Recent studies have linked to tumor progression, metastasis, chemoresistance, highlighting its potential as both biomarker therapeutic precision oncology. This...
Water networks in protein interfaces can complement direct interactions contributing significantly to molecular recognition, function, and stability of association. Thus, water be seen as an extension or addition structural features, which may add plenty information interfacial definition. However, solvent is frequently neglected interaction studies. Analysis the contained PDB essential achieve more accurate descriptions interfaces. With this aim, we have used SCOWLP database...
Protein interactions are essential for coordinating cellular functions. Proteomic studies have already elucidated a huge amount of protein-protein that require detailed functional analysis. Understanding the structural basis each individual interaction through their determination is necessary, yet an unfeasible task. Therefore, computational tools able to predict protein binding regions and recognition modes required rationalize putative molecular functions proteins. With this aim, we...
Alternative splicing acts on transcripts from almost all human multi-exon genes. Notwithstanding its ubiquity, fundamental ramifications of protein expression remain unresolved. The number and identity spliced that form stably folded proteins the sources considerable debate, due largely to low coverage experimental methods resulting absence negative data. We circumvent this issue by developing a semi-supervised learning algorithm, positive unlabeled for elucidation (PULSE;...
Magnetotactic bacteria are aquatic organisms that produce subcellular magnetic particles in order to orient the earth's geomagnetic field. MamE, a predicted HtrA protease required magnetite crystals magnetotactic bacterium Magnetospirillum magneticum AMB-1, was recently shown promote proteolytic processing of itself and two other biomineralization factors vivo Here, we have analyzed patterns three targets used this information reconstitute proteolysis with purified form MamE. MamE cleaves...