A5102999264- Computational Drug Discovery Methods
- Bacteriophages and microbial interactions
- RNA and protein synthesis mechanisms
- Fungal and yeast genetics research
- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Genomics and Phylogenetic Studies
- Influenza Virus Research Studies
- Genetics, Bioinformatics, and Biomedical Research
- RNA modifications and cancer
- RNA Research and Splicing
- Machine Learning in Bioinformatics
- vaccines and immunoinformatics approaches
- Bacterial Genetics and Biotechnology
- Vibrio bacteria research studies
- Lysosomal Storage Disorders Research
- SARS-CoV-2 and COVID-19 Research
- Cellular transport and secretion
- Gene expression and cancer classification
- Analytical Chemistry and Chromatography
- Infectious Diseases and Tuberculosis
- Chromosomal and Genetic Variations
- Protein Structure and Dynamics
- Metabolomics and Mass Spectrometry Studies
- Macrophage Migration Inhibitory Factor
Institut Pasteur
2015-2024
Bharath University
2023
Vaxine (Australia)
2018-2023
Université Paris Cité
2022-2023
Centre National de la Recherche Scientifique
2013-2022
Ahmedabad University
2014-2022
Department of Genomes & Genetics
2021
Macquarie University
2008-2019
Flinders University
2018
Génomique Bioinformatique et Applications
2016
Roland Brosch and colleagues report whole-genome sequencing of tubercle bacilli with smooth colony morphology, also known as Mycobacterium canetti and/or prototuberculosis, obtained from humans tuberculosis geographically diverse regions. Their comparative genomic analysis other M. complex members identifies extensive recombination provides insights into the evolution mycobacteria. The authors that morphology show reduced persistence virulence compared to strains in infection experiments...
High-throughput CRISPR-Cas9 screens have recently emerged as powerful tools to decipher gene functions and genetic interactions. Here we use a genome-wide library of guide RNAs direct the catalytically dead Cas9 (dCas9) block transcription in Escherichia coli. Using machine-learning approach, reveal that sharing specific 5-nucleotide seed sequences can produce strong fitness defects or even kill E. coli regardless other 15 nucleotides sequence. This effect occurs at high dCas9 concentrations...
Significance Whereas most of the more than 130 described mycobacterial species are harmless saprophytes, Mycobacterium tuberculosis , human tuberculosis-causing agent, represents one deadliest bacterial pathogens in history humankind. To explore mechanisms behind this spectacular evolutionary trajectory toward pathogenicity, we have experimentally investigated faculty different mycobacteria conducting horizontal gene transfer (HGT). Our studies identified unique chromosomal DNA between...
Abstract Mycobacterium tuberculosis (Mtb) strains are classified into different phylogenetic lineages (L), three of which (L2/L3/L4) emerged from a common progenitor after the loss MmpS6/MmpL6-encoding Mtb-specific deletion 1 region (TbD1). These TbD1-deleted “modern” responsible for globally-spread epidemics, whereas TbD1-intact “ancestral” tend to be restricted specific geographical areas, such as South India and East Asia (L1) or Africa (L7). By constructing characterizing panel...
Amongst the highly diverse Escherichia coli population, ST131-O25b:H4 clonal complex is particularly worrisome as it associated with a high level of antibiotic resistance. The lack new antibiotics, worldwide continuous increase infections caused by MDR bacteria and need for narrow-spectrum antimicrobial agents have revived interest in phage therapy. In this article, we describe virulent bacteriophage, LM33_P1, which specifically infects O25b strains, provide data related to its therapeutic...
The current approach to screen for drug-like molecules is sieve with biochemical properties suitable desirable pharmacokinetics and reduced toxicity, using predominantly biophysical of chemical compounds, based on empirical rules such as Lipinski's "rule five" (Ro5). For over a decade, Ro5 has been applied combinatorial drugs ligands, in the search lead compounds. Unfortunately, till date, clear distinction between non-drugs not achieved. trend seek out which show metabolite-likeness. In...
Trinucleotide repeat expansions are responsible for more than two dozens severe neurological disorders in humans. A double-strand break between short CAG/CTG trinucleotide repeats was formerly shown to induce a high frequency of contractions yeast. Here, using dedicated TALEN, we show that induction into heterozygous yeast diploid cells results gene conversion the tract with near 100% efficacy, deleting tract. Induction same TALEN homozygous diploids leads both final length 3–13 triplets,...
The numerous yeast genome sequences presently available provide a rich source of information for functional as well evolutionary genomics but unequally cover the large phylogenetic diversity extant yeasts. We present here complete sequence nuclear haploid-type strain Kuraishia capsulata (CBS1993T), nitrate-assimilating Saccharomycetales uncertain taxonomy, isolated from tunnels insect larvae underneath coniferous barks and characterized by its copious production extracellular...
The recent public availability of the human metabolome and natural product datasets has revitalized "metabolite-likeness" "natural product-likeness" as a drug design concept to lead libraries targeting specific pathways. Many reports have analyzed physicochemical property space biologically important datasets, with only few comprehensively characterizing scaffold diversity in biological interest. With large collections high quality data currently available, we carried out comparative...
Gaucher disease (GD) is the most common glycolipid storage disorder resulting from glucocerebrosidase deficiency due to mutations in GBA gene. Study was performed 33 unrelated patients with low β-glucosidase activity leukocytes and/or fibroblasts. The exons and exon–intron boundaries of gene were bidirectionally sequenced using an automated sequencer. Mutations confirmed parents looked up public databases, silico analysis carried for novel mutations. We identified two missense G289A...
It is unclear how gene order within the chromosome influences genome evolution. Bacteria cluster transcription and translation genes close to replication origin (oriC). In Vibrio cholerae, relocation of s10-spc-α locus (S10), major ribosomal protein genes, ectopic genomic positions shows that its relative distance oriC correlates a reduction in growth rate, fitness, infectivity. To test long-term impact this trait, we evolved 12 populations V. cholerae strains bearing S10 at an oriC-proximal...
The customary medicinal plant knowledge possessed by the Australian Aboriginal people is a significant resource. Published information on it scattered throughout literature, in heterogeneous data formats, and among various communities across Australia, due to multiplicity of languages. This ancient at risk loss biodiversity, cultural impact demise many its custodians. We have developed Customary Medicinal Knowledgebase (CMKb), an integrated multidisciplinary resource, document, conserve...
Transforming growth factor β1 (TGF-β1) is a master cytokine in many biological processes, including tissue homeostasis, epithelial-to-mesenchymal transition, and wound repair. Here, we report that four half LIM-only protein 2 (FHL2) critical regulator of TGF-β1 expression. Devoid DNA-binding domain, FHL2 transcriptional cofactor plays the role coactivator or corepressor, depending on cell promoter contexts. We detected association with promoter, which showed higher activity Fhl2-/- cells...
Abstract Copy number variation of chromosomal segments is now recognized as a major source genetic polymorphism within natural populations eukaryotes, well possible cause diseases in humans, including cancer, but its molecular bases remain incompletely understood. In the baker’s yeast Saccharomyces cerevisiae , variety low-order amplifications (segmental duplications) were observed after adaptation to limiting environmental conditions or recovery from gene dosage imbalance, and interpreted...
Infections due to parasitic nematodes are common causes of morbidity and fatality around the world especially in developing nations. At present however, there only three major classes drugs for treating human nematode infections. Additionally scientific knowledge on mechanism action reason resistance these is poorly understood. Commercial incentives design that endemic countries limited therefore, virtual screening academic settings can play a vital role discovering novel useful against...
27 years after the yeast genome sequencing, function of many ORFs remain unknown. Despite evolutionary distance between human and yeast, homology with conserved DEAH/DExH-box helicase domains allowed us to list DHX29, DHX36 DHX57 as three putative homologs Ylr419wp. Functional studies first linked Ylr419w protein translating ribosome cross-linking analysis cDNA (CRAC) experiments determined precise region Ylr419wp in contact ribosome. It corresponds loop h16 helix 18S rRNA designing...
Abstract Combinatorial synthesis and high‐throughput screening (HTS) are playing increasingly important roles in chemoinformatics. This review gives an overview of the strategies available for library design compound selection. Although traditional approach diversity‐oriented continues to be criterion lead generation, nevertheless, pharmacokinetic properties also widely recognized selection generating libraries. We summarize all current molecular similarity diversity methods employed...
Abstract Previously, we have identified a putative novel rapidly growing Mycobacterium species, referred to as TNTM28, recovered from the sputum of an apparently immunocompetent young man with underlying pulmonary disease. Here provide thorough characterization TNTM28 genome sequence, which consists one chromosome 5,526,191 bp 67.3% G + C content, and total 5193 predicted coding sequences. Phylogenomic analyses revealed deep-rooting relationship fortuitum complex, thus suggesting new...
(−)-Balanol is an ATP-mimicking inhibitor that non-selectively targets protein kinase C (PKC) isozymes and cAMP-dependent (PKA). While PKA constantly shows tumor promoting activities, PKC can ambiguously be promoters or suppressors. In particular, PKCε frequently implicated in tumorigenesis a potential target for anticancer drugs. We recently reported the C5(S)-fluorinated balanol analogue (balanoid 1c) had improved binding affinity selectivity but not to other novel isozymes, which share...
Abstract Gene amplification has been observed in different organisms response to environmental constraints, such as limited nutrients or exposure a variety of toxic compounds, conferring them with specific phenotypic adaptations via increased expression levels. However, the presence multiple gene copies natural genomes generally not found absence functional selection. Here, we show that massive chromosomal locus (up 880 per cell) occurs any direct selection, and is associated low-order...
Background Swertiamarin, a secoiridoid glycoside is found in abundant quantity Enicostemma Littorale herb and the main constituent responsible for anti-diabetic anti-obesity effects of plant extract. It has been reported to act on various enzymes transcription factors involved glucose lipid metabolism, including inhibition enzyme HMG-CoA reductase which might be one mechanisms antihyperlipidaemic activity. However, owing its high water solubility, it low plasma half life; thus we have...