A5085498126- Trypanosoma species research and implications
- Research on Leishmaniasis Studies
- Insect symbiosis and bacterial influences
- Glycosylation and Glycoproteins Research
- RNA and protein synthesis mechanisms
- 14-3-3 protein interactions
- Protein Tyrosine Phosphatases
- Biochemical and Molecular Research
- Ubiquitin and proteasome pathways
- Bioinformatics and Genomic Networks
- Parasitic Infections and Diagnostics
- Microbial Natural Products and Biosynthesis
- Advanced Proteomics Techniques and Applications
- Studies on Chitinases and Chitosanases
- Toxoplasma gondii Research Studies
- RNA modifications and cancer
- ATP Synthase and ATPases Research
- Enzyme Structure and Function
- Viral Infections and Immunology Research
- Protein Kinase Regulation and GTPase Signaling
- CRISPR and Genetic Engineering
- Lysosomal Storage Disorders Research
- Herpesvirus Infections and Treatments
- Viral Infectious Diseases and Gene Expression in Insects
- Galectins and Cancer Biology
Wellcome Centre for Anti-Infectives Research
2017-2025
University of Dundee
2016-2025
Wellcome Trust
2018-2025
Czech Academy of Sciences
2019
University of Rome Tor Vergata
2007-2017
MRC Protein Phosphorylation and Ubiquitylation Unit
2011-2014
Istituto Superiore di Sanità
2002-2003
Created with both in vitro and vivo data, NetPhorest is an atlas of consensus sequence motifs for 179 kinases 104 phosphorylation-dependent binding domains reveals new insight into signaling.
Abstract Motivation: The 14-3-3 family of phosphoprotein-binding proteins regulates many cellular processes by docking onto pairs phosphorylated Ser and Thr residues in a constellation intracellular targets. Therefore, there is pressing need to develop new prediction methods that use an updated set 14-3-3-binding motifs for the identification targets prioritize downstream analysis >2000 potential interactors identified high-throughput experiments. Results: Here, comprehensive from...
Understanding the consequences on host physiology induced by viral infection requires complete understanding of perturbations caused virus proteins cellular protein interaction network. The VirusMINT database (http://mint.bio.uniroma2.it/virusmint/) aims at collecting all interactions between and human reported in literature. currently stores over 5000 involving more than 490 unique from 110 different strains. whole data set can be easily queried through search pages results displayed with a...
Members of the SH2 domain family modulate signal transduction by binding to short peptides containing phosphorylated tyrosines. Each displays a distinct preference for sequence context residue. We have developed high-density peptide chip technology that allows probing affinity most domains large fraction entire complement tyrosine phosphopeptides in human proteome. Using this technique, we experimentally identified thousands putative SH2-peptide interactions more than 70 different domains....
We present a methodology using in vivo crosslinking combined with HPLC-MS for the global analysis of endogenous protein complexes by correlation profiling. Formaldehyde crosslinked were extracted high yield denaturing buffers that maintained complex solubility during chromatographic separation. show this efficiently detects both integral membrane and membrane-associated complexes,in addition to soluble complexes, allowing identification not accessible native extracts. compare detected...
Visceral leishmaniasis (VL), caused by the protozoan parasites Leishmania donovani and L. infantum, is responsible for ∼30 000 deaths annually. Available treatments are inadequate, there a pressing need new therapeutics. N-Myristoyltransferase (NMT) remains one of few genetically validated drug targets in these parasites. Here, we sought to pharmacologically validate this enzyme Leishmania. A focused set 1600 pyrazolyl sulfonamide compounds was screened against major NMT robust...
Background:Trypanosoma brucei is a protozoan parasite and etiological agent of human animal African trypanosomiasis. It has complex life cycle, but the most studied cellular types are in vitro cultivated bloodstream- procyclic-forms. These correspond to replicating, mammalian host bloodstream-dwelling, slender trypomastigotes tsetse vector midgut-dwelling procyclic lifecycle stages, respectively. Several proteomics studies have reported differential abundance proteins between these cell...
Medicines based on messenger RNA (mRNA) hold immense potential, as evidenced by their rapid deployment COVID-19 vaccines. However, worldwide distribution of mRNA molecules has been limited thermostability, which is fundamentally the intrinsic instability to a chemical degradation reaction called in-line hydrolysis. Predicting an molecule key task in designing more stable RNA-based therapeutics. Here, we describe crowdsourced machine learning competition ('Stanford OpenVaccine') Kaggle,...
Missense PTPN11 mutations cause Noonan and LEOPARD syndromes (NS LS), two developmental disorders with pleiomorphic phenotypes. encodes SHP2, an SH2 domain-containing protein tyrosine phosphatase functioning as a signal transducer. Generally, different substitutions of particular amino acid residue are observed in these diseases, indicating that the crucial factor is being replaced. For few codons, only one substitution observed, suggesting possibility specific roles for introduced. We...
Density-enhanced phosphatase-1 (DEP-1) is a trans-membrane receptor protein-tyrosine phosphatase that plays recognized prominent role as tumor suppressor. However, the mechanistic details underlying its function are poorly understood because primary physiological substrate(s) have not been firmly established. To shed light on mechanisms anti-proliferative of this phosphatase, we set out to identify new DEP-1 substrates by novel approach based screening high density peptide arrays. The...
Hundreds of candidate 14-3-3-binding (phospho)proteins have been reported in publications that describe one interaction at a time, as well high-throughput 14-3-3-affinity and mass spectrometry-based studies. Here, we transcribed these data into common format, deposited the collated from low-throughput studies MINT (http://mint.bio.uniroma2.it/mint), compared low- VisANT graphs are easy to analyze extend. Exploring prompted questions about technical biological specificity, which were...
The dimeric 14-3-3 proteins dock onto pairs of phosphorylated Ser and Thr residues on hundreds proteins, thereby regulate many events in mammalian cells. To facilitate global analyses these interactions, we developed a web resource named ANIA: ANnotation Integrated Analysis the interactome, which integrates multiple data sets 14-3-3-binding phosphoproteins. ANIA also pinpoints candidate phosphosites using predictor algorithms, assisted by our recent discovery that human 14-3-3-interactome is...
Cryptosporidiosis is a diarrheal disease caused by infection with Cryptosporidium spp. parasites and leading cause of death in malnourished children worldwide. The only approved treatment, nitazoxanide, has limited efficacy this at-risk patient population. Additional safe therapeutics are urgently required to tackle unmet medical need. However, the development anti-cryptosporidial drugs hindered lack understanding optimal compound properties treat gastrointestinal infection. To address...
14-3-3 proteins regulate cellular responses to stimuli by docking onto pairs of phosphorylated residues on target proteins. The present study shows that the human 14-3-3-binding phosphoproteome is highly enriched in 2R-ohnologues, which are families two four members were generated rounds whole genome duplication at origin vertebrates. We identify 2R-ohnologue whose share a 'lynchpin', defined as phosphosite conserved across given family, and aligns with Ser/Thr residue pro-orthologues from...
We describe a single-step centrifugal elutriation method to produce synchronous Gap1 (G1)-phase procyclic trypanosomes at scale amenable for proteomic analysis of the cell cycle. Using ten-plex tandem mass tag (TMT) labeling and spectrometry (MS)-based proteomics technology, expression levels 5325 proteins were quantified across cycle in this parasite. Of these, 384 classified as cell-cycle regulated subdivided into nine clusters with distinct temporal regulation. These groups included many...
Abstract A systematic evaluation of how model architectures and training strategies impact genomics performance is needed. To address this gap, we held a DREAM Challenge where competitors trained models on dataset millions random promoter DNA sequences corresponding expression levels, experimentally determined in yeast. For robust the models, designed comprehensive suite benchmarks encompassing various sequence types. All top-performing used neural networks but diverged strategies. dissect...
There is growing evidence that tyrosine phosphatases display an intrinsic enzymatic preference for the sequence context flanking target phosphotyrosines. On other hand, substrate selection in vivo decisively guided by enzyme-substrate connectivity protein interaction network. We describe here a system wide strategy to infer physiological substrates of protein-tyrosine phosphatases. Here we integrate, Bayesian model, proteome about vitro preference, as determined novel high-density peptide...
<ns4:p><ns4:bold>Background</ns4:bold>: Cellular proteins vary significantly in both abundance and turnover rates. These parameters depend upon their rates of synthesis degradation it is useful to have access data on protein when, for example, designing genetic knock-down experiments or assessing the potential usefulness covalent enzyme inhibitors. Little known about nature regulation <ns4:italic>Trypanosoma brucei</ns4:italic>, etiological agent human animal African...
Although genome-wide polycistronic transcription places major emphasis on post-transcriptional controls in trypanosomatids, messenger RNA cis-regulatory untranslated regions (UTRs) have remained largely uncharacterised. Here, we describe a genome-scale massive parallel reporter assay coupled with 3'-UTR-seq profiling the African trypanosome and identify thousands of regulatory UTRs. Increased translation efficiency was associated dosage adenine-rich poly-purine tracts (pPuTs). An independent...
Kinetoplastid parasites cause diseases that threaten human and animal health. To survive transitions between vertebrate hosts insect vectors, these rely on precise regulation of gene expression to adapt environmental changes. Since in kinetoplastids is primarily post-transcriptional, developing efficient genetic tools for modifying genes at their endogenous loci while preserving regulatory mRNA elements crucial studying complex biology. We present a CRISPR/Cas9-based tagging system preserves...
Transcription of protein coding genes in trypanosomatids is atypical and almost exclusively polycistronic. In Trypanosoma brucei, approximately 150 polycistrons, 8000 genes, are constitutively transcribed by RNA polymerase II. II promoters unconventional characterised regions chromatin enriched for histones with specific patterns post-translational modification on their highly divergent N-terminal tails. To investigate the roles histone tail-residues gene expression control T. we engineered...
Bloodstream-form African trypanosomes display mono-telomeric expression of a Variant Surface Glycoprotein (VSG) gene in an inter-chromosomally bridged transcription and splicing compartment, such that the dominant produces 10,000 times more transcript than excluded VSG genes. Antigenic variation, whereby parasites switch to express other VSGs, then underpins robust host immune evasion strategy. Specific chromatin RNA-associated factors are required maintain exclusion, but our understanding...