A5045821751- interferon and immune responses
- Tuberculosis Research and Epidemiology
- Bacterial Genetics and Biotechnology
- RNA and protein synthesis mechanisms
- Immune cells in cancer
- Bacteriophages and microbial interactions
- Phytochemical compounds biological activities
- Mycobacterium research and diagnosis
- Antimicrobial Peptides and Activities
- Antibiotic Resistance in Bacteria
- Cancer Mechanisms and Therapy
- DNA and Nucleic Acid Chemistry
- RNA regulation and disease
- Microbial Community Ecology and Physiology
- Immunotherapy and Immune Responses
- Enzyme Production and Characterization
- Biochemical and Structural Characterization
- Infectious Diseases and Tuberculosis
- Genomics and Chromatin Dynamics
- Genomics and Phylogenetic Studies
- Monoclonal and Polyclonal Antibodies Research
- Water Treatment and Disinfection
- African history and culture studies
- RNA modifications and cancer
- Vibrio bacteria research studies
Boston University
2016-2023
National University of Ireland
2023
Pulmonary Associates
2020
New York University
2012-2014
Bose Institute
2000-2012
Howard Hughes Medical Institute
2011-2012
Rutgers, The State University of New Jersey
2011-2012
Indian Institute of Management Calcutta
2000
During transcription initiation, RNA polymerase (RNAP) binds and unwinds promoter DNA to form an RNAP-promoter open complex. We have determined crystal structures at 2.9 3.0 Å resolution of functional initiation complexes comprising Thermus thermophilus polymerase, σ(A), a fragment corresponding the bubble downstream double-stranded The show that σ recognizes -10 element discriminator through interactions include unstacking insertion into pockets three bases RNAP -4/+2 region pocket +2 base....
Efficient repair of DNA double strand breaks and interstrand cross-links requires the homologous recombination (HR) pathway, a potentially error-free process that utilizes sequence as template. A key player in HR is RAD51, eukaryotic ortholog bacterial RecA protein. RAD51 can polymerize on to form nucleoprotein filament facilitates both search for sequences subsequent invasion required initiate HR. Because its pivotal role HR, subject numerous positive negative regulatory influences. Using...
The mechanism by which only some individuals infected with Mycobacterium tuberculosis develop necrotic granulomas progressive disease while others form controlled that contain the infection remains poorly defined. Mice carrying sst1-suscepible (sst1S) genotype inflammatory lung lesions, similar to human (TB) granulomas, are linked macrophage dysfunction, their congenic counterpart (B6) mice do not. In this study we report (a) sst1S macrophages developed aberrant, biphasic responses TNF...
Macrophages contribute to host immunity and tissue homeostasis via alternative activation programs. M1-like macrophages control intracellular bacterial pathogens tumor progression. In contrast, M2-like shape reparative microenvironments that can be conducive for pathogen survival or growth. An imbalance of these phenotypes may perpetuate sites chronic unresolved inflammation, such as infectious granulomas solid tumors. We have found plant-derived synthetic rocaglates sensitize low...
Understanding cell state transitions and purposefully controlling them to improve therapies is a longstanding challenge in biological research medicine. Here, we identify transcriptional signature that distinguishes activated macrophages from the tuberculosis (TB) susceptible resistant mice. We then apply cSTAR (cell transition assessment regulation) approach data screening-by-RNA sequencing chemical perturbations shift of tumor necrosis factor (TNF)-activated TB-susceptible toward...
Sulfur oxidation in Pseudaminobacter salicylatoxidans KCT001 is rendered by the combined action of several enzymes encoded a thiosulfate-inducible sox operon. In this study it has been conclusively demonstrated insertional mutagenesis that regulatory gene operon soxR, which encodes DNA-binding protein belonging to ArsR-SmtB family. SoxR was found bind two promoter-operator segments within cluster, one (wx) located between soxW and soxX controls expression sulfur-oxidation genes through soxD...
Abstract Drug-resistant bacteria represent a significant global threat. Given the dearth of new antibiotics, host-directed therapies (HDTs) are especially desirable. As IFN-gamma (IFNγ) plays central role in host resistance to intracellular bacteria, including Mycobacterium tuberculosis , we searched for small molecules augment IFNγ response macrophages. Using an interferon-inducible nuclear protein Ipr1 as biomarker macrophage activation, performed high-throughput screen and identified that...
In the mycobacterial plasmid pAL5000 replication region, genes repA and repB are organized in an operon. Earlier, a RepB-dependent origin binding activity was detected Escherichia coli cells expressing repA-repB This maximal when expression of two coupled (A. Basu, M. Chawla-Sarkar, S. Chakrabarti, K. Das Gupta, J. Bacteriol. 184:2204-2214, 2002). this study we have shown that translational coupling makes significant difference structure function RepB. When to repA, polypeptide folded into...
ABSTRACT Tuberculosis remains a critical infectious disease world-wide. The development of novel therapeutic strategies requires greater understanding host factors that contribute to susceptibility. A major unknown in TB pathogenesis is the mechanism necrosis granulomas leads massive lung tissue damage and cavity formation necessary for pathogen transmission. In humans, progression has been linked hyperactivity type I IFN (IFN-I) pathway, primary cause which elusive. We studied mechanistic...
Mycobacterial plasmid pAL5000 represents a family of plasmids found mostly in the Actinobacteria. It replicates using two plasmid-encoded proteins, RepA and RepB. While BLAST searches indicate that is replicase protein, evolutionary connection RepB cannot be established, as no significant homologous partner (E < 10(-3)) outside can identified. To obtain insight into structure-function connections RepB, an investigation was undertaken homology modeling, phylogenetic, mutational analysis...
Plasmid pAL5000 represents a family of relatively newly discovered cryptic plasmids in gram-positive Actinomycetes bacteria. The replication regions these comprise bicistronic operon, repA-repB, encoding two proteins. Located upstream is cis-acting element that functions as the origin replication. It comprises an approximately 200-bp segment spanning binding sites for protein RepB, low-affinity (L) site and high-affinity (H) separated by 40-bp spacer sequence. trajectory DNA RepB-origin...
Here, we present a streamlined protocol for assessing intracellular Mycobacterium tuberculosis (Mtb) loads in macrophages. This describes the simultaneous assessment of macrophage viability using automated microscopy. Further, detail quantification mycobacterial rapid, inexpensive, and accurate approach DNA isolation from paraformaldehyde-fixed Simultaneous bacterial internal standard allows precise effects perturbations on Mtb host cells while accounting technical artifacts. For complete...
Necrosis in the tuberculous granuloma is a hallmark of tuberculosis that enables pathogen survival and transmission. Susceptibility to several other intracellular bacteria controlled by mouse genetic locus, sst1, mice carrying sst1-suscepible (sst1S) genotype develop necrotic inflammatory lung lesions, similar human TB granulomas. Our previous work established increased disease severity sst1S reflects dysfunctional macrophage effector or tolerance mechanisms, but molecular mechanisms have...
L1 is a lysogenic phage of mycobacteria, which along with L5 and D29 constitute closely linked family homoimmune mycobacteriophages. These phages can be potentially used for genetic engineering mycobacteria diagnosis mycobacterial infection. The effectiveness such based systems depends on the efficiency they infect grow within target cells. While working L1c1ts temperature sensitive mutant L1, we observed that high yielding stocks were generated by repeated passage through host,...
Abstract Understanding cell state transitions and purposefully controlling them to improve therapies is a longstanding challenge in biological research medicine. Here, we identify transcriptional signature that distinguishes activated macrophages from TB-susceptible TB-resistant mice. We then apply the cSTAR (cell State Transition Assessment Regulation) approach data screening-by-RNA sequencing chemical perturbations shift the. of towards cells. Finally, demonstrate compounds identified with...
Abstract Macrophages contribute to host immunity and tissue homeostasis via alternative activation programs. M1-like macrophages control intracellular bacterial pathogens tumor progression. In contrast, M2-like shape reparative microenvironments that can be conducive for pathogen survival or growth. An imbalance of these phenotypes may perpetuate sites chronic unresolved inflammation, such as infectious granulomas solid tumors. We have found plant-derived synthetic rocaglates sensitize low...
Macrophages contribute to host immunity and tissue homeostasis via alternative activation programs. M1-like macrophages control intracellular bacterial pathogens tumor progression. In contrast, M2-like shape reparative microenvironments that can be conducive for pathogen survival or growth. An imbalance of these phenotypes may perpetuate sites chronic unresolved inflammation, such as infectious granulomas solid tumors. We have found plant-derived synthetic rocaglates sensitize low...