A5087187840- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- RNA and protein synthesis mechanisms
- Statistical Methods and Inference
- Bayesian Modeling and Causal Inference
- Gene expression and cancer classification
- Cancer therapeutics and mechanisms
- Computational Drug Discovery Methods
- Advanced Causal Inference Techniques
- Bacterial Genetics and Biotechnology
- Bacteriophages and microbial interactions
- Biochemical and Molecular Research
- Genomics and Phylogenetic Studies
- Advanced biosensing and bioanalysis techniques
- Enzyme Structure and Function
- Chemical Synthesis and Analysis
- Antibiotic Resistance in Bacteria
- RNA Interference and Gene Delivery
- Infectious Diseases and Tuberculosis
- Evolution and Genetic Dynamics
- Molecular Sensors and Ion Detection
- Immune responses and vaccinations
- Pneumocystis jirovecii pneumonia detection and treatment
- Escherichia coli research studies
- CRISPR and Genetic Engineering
Cornell University
2019-2024
Weill Cornell Medicine
2020-2024
Indian Institute of Science Bangalore
2014-2020
Antibacterial agents target the products of essential genes but rarely achieve complete inhibition. Thus, all-or-none definition essentiality afforded by traditional genetic approaches fails to discern most attractive bacterial targets: those whose incomplete inhibition results in major fitness costs. In contrast, gene "vulnerability" is a continuous, quantifiable trait that relates magnitude effect on fitness. We developed CRISPR interference-based functional genomics method systematically...
Current chemotherapy against Mycobacterium tuberculosis (Mtb), an important human pathogen, requires a multidrug regimen lasting several months. While efforts have been made to optimize therapy by exploiting drug–drug synergies, testing new drug combinations in relevant host environments remains arduous. In particular, profoundly affect the bacterial metabolic state and efficacy, limiting accuracy of predictions based on vitro assays alone. this study, we utilized conditional Mtb knockdown...
Abstract Of the ~80 putative toxin‐antitoxin (TA) modules encoded by bacterial pathogen Mycobacterium tuberculosis ( Mtb ), three contain antitoxins essential for viability. One of these, Rv0060 (DNA ADP‐ribosyl glycohydrolase, DarG functions along with its cognate toxin Rv0059 transferase, DarT to mediate reversible DNA ADP‐ribosylation (Jankevicius et al ., 2016). We demonstrate that ‐DarG form a functional TA pair and essentiality darG is dependent on presence darT , but simultaneous...
cAMPhor: In the presence of cAMP, cAMPhor folds into a structure that binds DFHBI (green), increasing its fluorescence, while Alexa 647 (red) functions as normalizing dye. It can thus be used to spatially image cAMP quantitatively in membrane-bound compartments. As service our authors and readers, this journal provides supporting information supplied by authors. Such materials are peer reviewed may re-organized for online delivery, but not copy-edited or typeset. Technical support issues...
Deep sequencing of transposon mutant libraries (or TnSeq) is a powerful method for probing essentiality genomic loci under different environmental conditions. Various analytical methods have been described identifying conditionally essential genes whose tolerance insertions varies between two However, large-scale experiments involving many conditions, needed that exhibit significant variability in across multiple conditions.In this paper, we introduce novel statistical with insertion counts...
It is a truth universally acknowledged that an observed association without known mechanism must be in want of causal estimate. However, estimation from observational data often relies on the (untestable) assumption `no unobserved confounding'. Violations this can induce bias effect estimates. In principle, such could invalidate or reverse conclusions study. some cases, we might hope influence confounders weak relative to `large' estimated effect, so qualitative are robust confounding. The...
The cyclic AMP receptor protein (CRP) family of transcription factors consists global regulators bacterial gene expression. Here, we identify two paralogous CRPs in the genome Mycobacterium smegmatis that have 78% identical sequences and characterize them biochemically functionally. proteins (MSMEG_0539 MSMEG_6189) show differences cAMP binding affinity, trypsin sensitivity, to a CRP site identified upstream msmeg_3781 gene. MSMEG_6189 binds readily absence cAMP, while MSMEG_0539 presence...
Abstract Characterizing genetic essentiality across various conditions is fundamental for understanding gene function. Transposon sequencing (TnSeq) a powerful technique to generate genome-wide profiles in bacteria and has been extensively applied Mycobacterium tuberculosis (Mtb). Dozens of TnSeq screens have yielded valuable insights into the biology Mtb vitro, inside macrophages, model host organisms. Despite their value, these not standardized or collated single, easily searchable...
<title>Abstract</title> The increasing prevalence of antimicrobial resistance is an important challenge that warrants new approaches to antibiotic development. Currently, all antibiotics inhibit biological processes. To explore whether activation a biochemical pathway can elicit bactericidal effects we engineered variants Mycobacterium tuberculosis ATP-phosphoribosyltransferase (ATP-PRT) are resistant allosteric inhibition by L-histidine, leading supraphysiological ATP-PRT and L-histidine...
Chemical-genetics (C-G) experiments can be used to identify interactions between inhibitory compounds and bacterial genes, potentially revealing the targets of drugs, or other functionally interacting genes pathways. C-G involve constructing a library hypomorphic strains with essential that knocked-down, treating it an compound, using high-throughput sequencing quantify changes in relative abundance individual mutants. The hypothesis is that, if target drug same pathway are present library,...
Abstract Deep sequencing of transposon mutant libraries (or TnSeq) is a powerful method for probing essentiality genomic loci under different environmental conditions. Various analytical methods have been described identifying conditionally essential genes whose tolerance insertions varies between two However, large-scale experiments involving many conditions, needed that exhibit significant variability in across multiple In this paper, we introduce novel statistical with insertion counts...
Abstract Current chemotherapy against Mycobacterium tuberculosis ( Mtb ), an important human pathogen, requires a multidrug regimen lasting several months. While efforts have been made to optimize therapy by exploiting drug-drug synergies, testing new drug combinations in relevant host environments remains arduous. In particular, profoundly affect the bacterial metabolic state and efficacy, limiting accuracy of predictions based on vitro assays alone. this study, we utilize conditional...
ADVERTISEMENT RETURN TO ISSUEPREVAddition/CorrectionORIGINAL ARTICLEThis notice is a correctionCorrection to Paralogous cAMP Receptor Proteins in Mycobacterium smegmatis Show Biochemical and Functional DivergenceRitu Sharma, Anisha Zaveri, Jayashree Gopalakrishnapai, Thiruneelakantan Srinath, Umesh Varshney, Sandhya S. Visweswariah* Cite this: Biochemistry 2015, 54, 2, 630Publication Date (Web):December 31, 2014Publication History Published online31 December 2014Published inissue 20 January...