Development of Novel methods for the Synthesis of Medicinally Important Amino-aryl-C-glyacosides
A class of naturally occurring molecules having an amino-aryl-C-glycoside moiety such as C-aryl-2-deoxy-3-amino has emerged as antibiotics with promising antitumor activities and is used as drugs for mitigation of leukemia and sarcoma against multi-drug-resistant bacteria (Fig 1A). However, availability and reproducibility limit their biological assay. Synthetic organic chemistry is a powerful tool to access such complex scaffolds and their analogues from easily available raw materials. One of the best precursors one can have for the synthesis of such scaffolds can be sugar enol ether also known as glycals. Here the major synthetic challenge is selective anomeric C-arylation and regio-selectively oxidize C-3 allylic ether to keto which can be easily converted to amines with desired stereochemistry via stereoselective reduction. Hence 3-keto-2-deoxy-C1-aryl glycals was chosen as a target (Fig 1B). We have established a one-step procedure for the synthesis of C-1 aryl enopyranones directly from commercially available glycals with aryl halides in the absence of strong base via the oxidative Mizoroki–Heck reaction and proposed mechanism (fig 1C). The results are published in Organic Biomolecular Chemistry Journal of Royal Society of Chemistry [Ref].
Reference: Synthesis of aryl enopyranones directly from glycals and aromatic halides to access 2-deoxy-β-C-aryl glycosides; Irshad Ahmad Zargar, Bisma Rasool, S. K. Bappa and Debaraj Mukherjee *,Org. Biomol. Chem., 2024, 22, 6941–6945-6941
Month Year : September - 2024
An interview to DD Bangla on Computer, Biotechnology and related subjects for the students by Prof. Shubhra Ghosh Dastidar
An interview to DD Bangla on Computer, Biotechnology and related subjects for the students by Prof. Shubhra Ghosh Dastidar.
Details Here
Month Year : October - 2024
Special Issue on "Statistical Physics and Complex Systems" in IJP edited by Profs. Deepak Dhar and Soumen Roy
Special Issue on "Statistical Physics and Complex Systems" in Indian Journal of Physics (Springer) edited by Profs. Deepak Dhar and Soumen Roy. Contributors include Profs. Marc Mezard, Bikas Chakrabarti, Paul Krapivsky, Sidney Redner, Matteo Marsili, Ram Ramaswamy, Mustansir Barma, and Edgar Roldan.
Month Year : October - 2024
Senior women scientist from Bose Institute selected for WIDUSHI Program of the WISE-KIRAN Division Department of Science and Technology, Government of India.
Protein-L-isoaspartyl methyltransferase (PIMT) is a repair enzyme which recognizes abnormal isoAspartate residues formed during ageing. The project proposes to look into the role of isoAspartate in fibril formation using mutants of Abeta peptides (hallmark for Alzheimer’s disease) containing isoAspartate, alpha-synuclein (hallmark for Parkinson’s disease) etc and how PIMT recognizes and repairs them. The findings may answer the basic question why nature has selected Alpha- over Beta- amino acid.
# isoAspartate
# Beta-amino acid
# Fibril formation
# Ageing
# PIMT protein
# Neurodegenerative diseases
Month Year : June - 2024
Development of novel methods to access medicinally important C-2 Thio branched Sugars via Radical Pathway and Their Late-stage Modifications
BE-7585A and rhodonocardin-A are naturally occurring polyketides featuring an angucyclic core structure with 2-thio sugars, noted for their potential anticancer properties (see Fig. 1). Both BE-7585A and rhodonocardin-A are believed to exert their anticancer effects through cellular pathways involved in cancer progression, and tumour growth inhibition. Development of strategies to access key intermediate C-2 thio branched sugar is required for biological study.
A novel C-H activation method was developed for the synthesis of 2-thio sugars using a less explored radical mechanism (fig2). Subsequent late-stage modifications of the resulting product revealed an unexpected rearrangement, mechanism of which deciphered in details [ref] from the control experiments conducted in our lab.
References:
Peroxodisulfate-assisted synthesis of 2-thiocyanato glycals and their transformation to C-2-thio acrylo/aryl nitrile-substituted glycals. Bisma Rasool, Irshad Ahmad Zargar, Sanchari Kundu and Debaraj Mukherjee*. Chemical Communication, July,2024, DOI: 10.1039/d4cc02201g
Month Year : July - 2024
Advancement in Carbohydrate Chemistry: Novel Approach for Synthesizing Disaccharides and Arylthiosugars
Carbohydrates such as 1-1 and 1-3 O/S-linked disaccharides act as a powerful tool to probe various biological processes and therefore have great importance in the field of glycobiology. These are embedded in various natural products and essential components of many bioactive molecules (fig1). Moreover, 3-thioglycosides have been employed in X-ray crystallographic investigations to image stable protein-carbohydrate complexes to gain crucial structural and mechanistic insights. Due to the growing importance of these structures, there is a pressing need to synthesize above glycol-molecules.
Recently Chen’s group discovered the S-glyco-modification at C-3 between protein cysteine and per-O-acetylated monosaccharide under cytosolic esterases into the cellular glycan which follows an elimination-addition mechanism. We have developed a new directing group (DG) assisted regio- and stereo-selective synthesis of such compounds under mild reaction condition. Thus we have C-3 axially oriented thio-sugars from 2-keto phenyl glycals under mild basic condition [ref 1]. Thereafter, the divergent synthesis of 1,3- and 1,1-disaccharides were developed using 2-benzoyl glycal and anomeric thiol and/or hydroxy sugar acceptors [Ref 2]. This new protocol, conducted under mild conditions at room temperature, not only simplifies the synthesis process but also delivers excellent yields and high selectivity. The regio- and stereoselectivity of the newly formed inter-glycosidic linkages are influenced by the nature of the glycal donor (D or L) and the anomeric acceptor.
References:
1. 2-Ketophenyl Assisted Biomimetic Synthesis of 3-Thio Substituted Glycals at Room Temperature. Irshad Ahmad Zargar, Norein Sakander, and Debaraj Mukherjee*. Eur. J. Org. Chem. 2023, e202300780.
2. Switchable reactivity of 2-benzoyl glycals towards stereoselective access of 1-3 and 1-1 S/O linked disaccharides. Irshad Ahmad Zargar, Bisma Rasool, Norein Sakander and Debaraj Mukherjee*. Chem. Commu
Month Year : August - 2024
Breakthrough in Disaccharide Synthesis Opens New Avenues for Complex Enzymatically Stable Mimetics
C-disaccharides are enzymatically stable analogues of O-glycosides. They are interconnected by carbon spacer (Fig 1a). Above class of molecules find application as therapeutics in different diseases areas and constitute core structure of several bioactive natural products (Fig. 1b). However, stereo-selective synthesis of such linkages remains a challenge.
A novel and convenient method for synthesizing C1-C2 interlinked disaccharides has been developed in our lab, offering significant advancements in carbohydrate chemistry. We have demonstrated an efficient approach using readily available iodo-glycals and unsubstituted glycals as starting materials (Fig 2). The method involves reacting ester-protected donor molecules with ether-protected acceptors under a Pd-Ag catalytic system. This reaction yields C-disaccharides featuring a C-3 vinyl ether linkage. The process allows for subsequent ring opening through Lewis acid treatment, leading to the formation of π-extended conjugated orthogonally protected chiral ketones. Reduction and global deprotection leads to fully saturated disaccharides that are notably stable against acid hydrolysis, marking a significant achievement in the stability and utility of these complex molecules [Ref]. This new synthesis pathway not only simplifies the creation of intricate disaccharide structures but also enhances the stability and functionality of these compounds, paving the way for more advanced research and applications in carbohydrate chemistry.
References:
1. Rasool, B., Zargar, I. A., Hussain, N., & Mukherjee, D. (2023). Pd-catalyzed synthesis of hetero 1, 2-interlinked C-disaccharides by coupling of iodo glycals with glycals. Chemical Communications, 59(59), 9090-9093.
Month Year : August - 2024
1st Prize at the 39th. Young Physicists' Colloquium (YPC 2024) organized by the Indian Physical Society
Ms. Chumki Nayak working with Prof. Achintya Singha, Department of Physical Sciences was awarded the 1st Prize at the 39th. Young Physicists' Colloquium (YPC 2024) organized by the Indian Physical Society.
Month Year : August - 2024
Participation and presentation of work "Direct and Sequential Breakup of 7Be on 12C at 5 MeV/u"at the “Euroschool on Exotic Beams” at Jyväskylä, Finland
We are delighted to share that Mr. Ritankar Mitra, working with Prof. Dhruba Gupta, Department of Physical Sciences, has been selected to participate and present his work "Direct and Sequential Breakup of 7Be on 12C at 5 MeV/u"at the “Euroschool on Exotic Beams” at Jyväskylä, Finland during Aug 25 - 31, 2024. The tour was fully sponsored by Euroschool.
Month Year : August - 2024
We report nucleic acid-targeting PROTAC (NA-TAC) molecules by conjugating DNA-binding and E3 ligase ligands.
Targeted protein degradation through PROteolysis TArgeting Chimeras (PROTACs) is a relatively new modality in cellular interventions. The minimum requirement for PROTACs to function is forming a tertiary complex of protein of interest (POI), E3 ligase, and the molecular glue PROTAC. Here, we propose a new approach to modulate the nano-environment interactome of a non-protein target through a plausible quaternary complex of interactome-biomolecule of interest (BOI)-PROTAC and E3 ligase. We report nucleic acid-targeting PROTAC (NA-TAC) molecules by conjugating DNA-binding and E3 ligase ligands. We demonstrate that NA-TACs can target the G-quadrupled DNA and induce elevated DNA damage and cytotoxicity compared to the conventional G-quadruplex binding ligands. Our new class of NA-TACs lays the foundation of small molecule-based non-protein targeting PROTACs for interactome and nanoenvironment mapping and nucleic acid-targeted precision medicines.
Tanga et al. Design and Synthesis of Nucleic Acid Nano-environment Interactome-Targeting Small Molecule PROTACs and Their Anticancer Activity. Nanoscale, 2024, In press.
Month Year : 2024-05-01
Organic Synthetic Small Molecules and Anticancer Drug Development
We develop synthetic small molecules for precision medicine applications. We combine these synthetic small molecules with CRISPR for chemogenetic studies for disease control.
Tanga et al. Cysteine-independent CRISPR-Associated Protein Labeling for Presentation and Co-delivery of Molecules Toward Genetic and Epigenetic Regulations. Chembiochem. 2024 Mar 26:e202400149. doi: 10.1002/cbic.202400149
Month Year : 2024-04-01
Cosmic Ray Air Shower array in Darjeeling
An air shower array of seven plastic scintillation detectors has been built and commissioned at an altitude of 2200 meters above sea level in the Eastern Himalayas (Darjeeling). Continuous measurement of shower rate using this array is going on since the end of January, 2018.Six detectors are kept at the vertices of a hexagon and one at the center of it. The distance between any two consecutive detectors is kept to be 8 m. Each detector element consists of four plastic scintillators of dimension 50 cm × 50 cm ×1 cm making the total active area of 1 m × 1 m. ll four scintillators of a detector are coupled with a single Photo Multiplier Tube (PMT) using a bundle of 48 wavelength shifting (WLS) fibers spread over the active area of the detector. The detector system is continuously measuring the number of cosmic ray showers. From this array it has been found that at an altitude of about 2200 m the average air shower rate is ∼1. 65Hz with an RMS of 0.24 and the 7-fold coincidence rate has been found to be ∼0.04 Hz with an RMS of 0.02.
Roy et al. Plastic scintillator detector array for detection of cosmic ray air shower, NIM A (in press)
Month Year : 2024-01-01
Low-Altitude rainfall occurred over Eastern Antarctica as a signature of global warming
Antarctica is known for the pristine polar continental area containing largest single-mass ice-sheet, which is very sensitive to recent climate change processes. The polar ice-sheet is a result of melting and formation of glaciers due to variation in snowfall. Our climate change study group of Environmental Sciences Section, Bose Institute led by Dr. Sanat Kumar Das, is investigating the effects of climate change processes over Antarctica. The group participated in the 36th Indian Scientific Expedition to Antarctica (36th ISEA) for this study. One of our objectives is to investigate the south polar precipitation over eastern Antarctica from ground-based observations at the Indian national permanent station for scientific research, Bharati. Micro-rain Radar and Optical Rain Gauge (ORG) were installed in campaign mode at Bharati. One of our major findings from this scientific expedition is a first of its kind observation of rain coming from very low altitudes, near 1 km, during summer, which is a clear indication of melting of snowfall and effect of global warming over eastern Antarctica. The figures show the temporal variation of rain-rate profiles observed by the ground-based radar and the surface raindrop sizes (Dm) with rainrate using ORG, both with 1-min cadence. Simulation studies are going on to investigate the cause of such low-altitude rainfall over Antarctica.
Month Year : 2024-01-01
Poor Air quality leading to high health risk in the Himalayan urban regions due to road-side garbage/biomass burning
Pollutants are scaled from ‘Good’ to ‘Severe’ in a scale (0-500) of air quality index (AQI) as per their toxicity and amount of loading into the atmosphere and the corresponding stress generated in different sensitive organs like heart and brain of the human body after breathing such polluted air, which leads to high health risks. Himalayan urban regions are highly polluted by particulate matter within 2.5-micron sizes (PM2.5), Carbon Monoxide (CO) and Nitrogen-di-Oxide (NO2) due to significant amount of emissions from various types of combustion processes. A winter-time road-campaign was carried out with very low-cost light-weight Arduino sensors installed on a mobile laboratory to investigate the air quality index over the eastern Himalayas in the surroundings of our Himalayan observatory at Darjeeling campus, Bose Institute (BI). Our mobile observatory covered the area within a radius of about 30 km surrounding the urban region of Darjeeling including tea gardens over hilly slopes (TG), and orange valley (OV) regions. This Himalayan urban region is situated about 2 km above mean sea level (amsl), and the lowest height of the valley included in this campaign is about 1 km amsl. High concentrations of toxic gases like CO and NO2 were observed that are produced from various types of local road-side combustions near Darjeeling and could not disperse easily due to low temperature and humid atmosphere. PM2.5 was also very high over the Himalayan urban region. The PM2.5 aerosols are mainly forming from toxic gases through gas-to-particle conversion, and primary particles like Black Carbon are directly injected into the atmosphere from biomass burning. The Himalayan air-quality, indicating ‘Very Poor’ on an average and ‘Severe’ at some places on the air quality index scale, is worsening for breathing, particularly for chronical respiratory patients, and leading to increased heath risks in winter over the Himalayas.
Month Year : 2024-01-01
We have established WUSCHEL, a transcription factor as an early marker for the onset of in vitro shoot morphogenesis. It will help for predictive plant transgenic development for the non-model plants.
We have studied the role of growth regulators behind in vitro shoot organogenesis and somatic embryogenesis in two plant systems, viz. tobacco (Nicotiana tabacum L. var. Jayasri) and Beta palonga R.K. Basu & K.K. Mukh. We have also correlated the phenomena of de differentiation with the relative expression of WUS (WUSCHEL) gene in a time-dependent manner. The results indicated that early WUS gene expression is a definite marker for in vitro shoot organogenesis in tobacco and Beta both in direct and indirect modes of regeneration. Additionally, we have performed a comparative homology modeling and in silico structural analysis of WUSCHEL proteins of B. palonga, B. vulgaris, and Arabidopsis to find out the commonality of the ligand binding site. The amino acids of the binding sites were identical (Arginine, Tryptophan, Proline, Asparagine, and Tyrosine) in the three materials under study; except two additional amino acids (Isoleucine and Alanine) in B. vulgaris
Sultana M et al, Early expression of WUSCHEL is a marker for in vitro shoot morphogenesis in tobacco and Beta palonga. Plant Cell, Tissue and Organ Culture (PCTOC) (2018) 134:277–288
https://doi.org/10.1007/s11240-018-1421-x
Month Year : 2024-01-01
Secondary cosmic gamma-ray flux in India during the Great American solar eclipse on 21st August 2017
We present the results from the measurement of secondary cosmic gamma-ray flux using a NaI(Tl) scintillator detector during a total solar eclipse. The unique feature of this experiment is that it was carried out at a place where the solar eclipse was not observable. The total solar eclipse of August 21, 2017, was visible in most of the regions of North America during the day, whereas India, falling on the other half of the globe missed this particular eclipse. Our aim was to measure and examine if there are any variations in the secondary cosmic ray (SCR) flux at Kolkata, India due to the occurrence of the eclipse in America. Detailed experimental techniques used for this experiment are mentioned in this article. Method of data analysis and results are presented. We observe unexpected decrement and increment in SCR flux in certain energy regions.
Roy S et al. A study of the secondary cosmic γ -ray flux in India during the Great American solar eclipse on 21st August 2017, Astrophys Space Sci (2020) 365:172
Month Year : 2024-01-01
Charging-up effect for a single mask triple GEM detector
With the advancement of the accelerator systems and the requirements of high luminosity particle beams to reach different physics goals, detectors with good position resolution and high rate handling capability have become essential for designing any High Energy Physics (HEP) experiments. The Gas Electron Multiplier (GEM) detectors are widely used in many HEP experiments as a tracking device because of their good spatial resolution and rate handling capability. The presence of the dielectric medium inside the active volume of the GEM detector changes its behaviourwhen exposed to external radiation. This mechanism is commonly referred as the charging-up effect. In this article, the effect of the charging-up phenomenon and the initial polarisation effect of the dielectric on thegain of the chamber are reported for a single mask triple GEM chamber with Ar/CO2 gas mixture.
Chatterjee et al., Study of charging-up effect for a single mask triple GEM detector, Nucl. Instr. and Meth. A 1014 (2021) 165749
Month Year : 2024-01-01
Prof. Debaraj Mukherjee, has joined editorial board of Journal of Carbohydrate Chemistry.
Prof. Debaraj Mukherjee, Department of Chemical Sciences, Bose Institute Kolkata has joined editorial board of Journal of Carbohydrate Chemistry in November 2023, a journal published byTaylor & Francis group which serves as an international forum for research advances involving the chemistry and biology of carbohydrates over last forty years upon invitation from Editor-in-Chief Prof. Zhongwu Guo – Department of Chemistry, University of Florida
Month Year : 2023-11-04
Heat shock response in Sulfolobus acidocaldarius and first implications for cross-stress adaptation
Sulfolobus acidocaldarius, a thermoacidophilic crenarchaeon, frequently encounters temperature fluctuations, oxidative stress, and nutrient limitations in its environment. Here, we employed a highthroughput transcriptomic analysis to examine how the gene expression of S. acidocaldarius changes when exposed to high temperatures (92 C). The data obtained was subsequently validated using quantitative reverse transcription-PCR (qRT-PCR) analysis. Our particular focus was on genes that are involved in the heat shock response, type-II Toxin-Antitoxin systems, and putative transcription factors. To investigate how S. acidocaldarius adapts to multiple stressors, we assessed the expression of these selected genes under oxidative and nutrient stresses using qRT-PCR analysis. The results demonstrated that the gene thb encoding the b subunit of the thermosome, as well as hsp14 and hsp20, play crucial roles in the majority of stress conditions. Furthermore, we observed overexpression of at least eight different TA pairs belonging to the type II TA systems under all stress conditions. Additionally, four common transcription factors: FadR, TFEb, CRISPR loci binding protein, and HTH family protein were consistently overexpressed across all stress conditions, indicating their significant role in managing stress. Overall, this work provides the first insight into molecular players involved in the cross-stress adaptation of S. acidocaldarius.
Bhowmick A et al, Heat shock response in Sulfolobus acidocaldarius and first implications for cross-stress adaptation. Research in Microbiology, 104106 (2023)
Month Year : 2023-08-01
CRSI Bronze Medal 2023
Dr. Debaraj Mukherjee, Professor, Department of Chemistry, Bose Institute, Kolkata has been awarded Bronze Medal with citation by the Chemical Research Society of India (CRSI) at the award ceremony held during 2nd - 5th Feb 2023 at Jawaharlal Nehru University (JNU), New Delhi by the President CRSI Padma Shri Prof. V. K Singh, IIT Kanpur. The Bronze Medal award is given to young researchers who have made significant contributions to research in Chemical Science.
Dr.Debaraj Mukherjee
Month Year : 2023-02-04
CRSI Best Poster Award 2023
Ms. Bisma Rasool, Student of Prof. Debaraj Mukherjee, Department of Chemistry ( registered under AcSIR) got Best Poster award for work entitled "One Pot Domino transformation of Glycals into Pyrano cis fusedmheterocycles via Nickel catalysis" by competing with 262 participants all over India by the Chemical Research Society of India (CRSI) at the award ceremony held during 2nd - 5th Feb 2023 at Jawaharlal Nehru University (JNU), New Delhi by the President CRSI Padma Shri Prof. V. K Singh, IIT Kanpur
Bisma Rasool,Monika Bhardwaj, Debaraj Mukherjee*
Month Year : 2023-02-04
Registration of sesame germplasm in ICAR repository
Professor Gaurab Gangopadhyay and his group from the Division of Plant Biology have developed inter-specific hybrid sesame, an oilseed crop, through molecular marker-assisted breeding. It has high oil content (52.9% w/w) with remarkable lignans (sesamin 61.2 ug/ml; sesamol 15.1 ug/ml). The genotype also is tolerant to charcoal rot disease (causal organism Macrophomina phaseolina). The Plant Germplasm Registration Committee (PGRC) of the Indian Council of Agricultural Research (ICAR) has certified the germplasm (R6 of sesame) with the registration number INGR22090 (IC0643978) and preserved it in their repository.
Month Year : 2022-10-30
Jukti tokko-Topic: Swasruddho tilottoma
A live talk show on DD Bangla on 31st August, 2022 which was based on Kolkata's air pollution. Dr Abhijit Chatterjee was invited as the Air Pollution expert and Advisor of Kolkata Municipal Corporation. Details Here
Month Year : 2022-09-01
Celebration of International Blue Sky Day, 7th September, 2021 at WBPCB, Kolkata
With a view to make the people aware, theme of the day “Healthy Air-Healthy Planet”, the day was observed and celebrated physically at the West Bengal Pollution Control Board. The link of the celebration was made open to all for better participation by all.
Details Here
Month Year : 2021-09-07
Network approach to mutagenesis sheds insight on phage resistance in mycobacteria
A rigorous yet general mathematical approach to mutagenesis, especially one capable of delivering systems-level perspectives would be invaluable. Such systems-level understanding of phage resistance is also highly desirable for phage-bacteria interactions and phage therapy research. Independently, the ability to distinguish between two graphs with a set of common or identical nodes and identify the implications thereof is important in network science. Herein we propose a measure called shortest path alteration fraction (SPAF) to compare any two networks by shortest paths, using sets. When SPAF is one, it can identify node pairs connected by at least one shortest path, which are present in either network but not both. Similarly, SPAF equaling zero identifies identical shortest paths, which are simultaneously present between a node pair in both networks. We study the utility of our measure theoretically in five diverse microbial species, to capture reported effects of well-studied mutations and predict new ones. We also scrutinise the effectiveness of our procedure through theoretical and experimental tests on Mycobacterium smegmatis mc2155 and by generating a mutant of mc2155, which is resistant to mycobacteriophage D29. This mutant of mc2155, which is resistant to D29 exhibits significant phenotypic alterations. Whole-genome sequencing identifies mutations, which cannot readily explain the observed phenotypes. Exhaustive analyses of protein-protein interaction network of the mutant and wild-type, using the machinery of topological metrics and differential networks does not yield a clear picture. However, SPAF coherently identifies pairs of proteins at the end of a subset of shortest paths, from amongst hundreds of thousands of viable shortest paths in the networks.The altered functions associated with the protein pairs are strongly correlated with the observed phenotypes
Sinha S et al, Bioinformatics [Oxford] 37, 213-220 (2021)
Month Year : 2021-08-20
Scale-free networks may not necessarily witness cooperation
Networks with a scale-free degree distribution are widely thought to promote co-operation in various games. We demonstrate that this need not necessarily be true. For the very same degree sequence and degree distribution, we present a range of possible behaviour. We reassess the perceived importance of hubs in a network towards the maintenance of cooperation. We also reevaluate the dependence of cooperation on network clustering and assortativity. In this figure red denotes the maintenance of cooperation and blue its absence for a wide variety of scale-free networks.
Nath et al, Euro Physics Letters [EPL], 134, 60002 (2021)
Month Year : 2021-08-17
Trends of mutation accumulation across global SARS-CoV-2 genomes: Implications for the evolution of the novel coronavirus
SARS-CoV-2 microevolution was studied in 71,703 whole-genomes sequenced worldwide until 21.08.2020. Globally, nsp1/nsp2 and orf7a/orf3a were the most mutation-ridden non-structural and structural genes respectively. Whole-genome phylogeny revealed that entities belonging to the early lineages are mostly spread over Asian countries. A transition:transversion ratio of 2.66 characterized SARS-CoV-2, with C→U and G→U being the predominant mutation-types. Missense mutations are positively selected mostly in structural genes; missense C→Us tend to usher hydrophobic amino acids.
Roy C et al, Trends of mutation accumulation across global SARS-CoV-2 genomes: Implications for the evolution of the novel coronavirus. Genomics [Elsevier], 112, 5331-5342 (2020)
Month Year : 2020-11-01
Exploration of a sulfidic marine deep subsurface discovered the existence of aerobic microbial life amidst anoxia
Metabolically active aerobic bacterial communities comprising both chemolithoautotrophs and chemooorganoheterotrophs were discovered along ∼3 m sediment horizons of the eastern Arabian Sea, where the bottom-water remains acutely hypoxic round the year and the subsurface contains high amounts of sulfide. The work was carried out in collaboration with the Geochemistry Group of Dr. Aninda Mazumdar at the CSIR-National Institute of Oceanography, Goa, India. The article was selected as an Editor's choice paper in the journal.
Bhattacharya S et al, Aerobic microbial communities in the sediments of a marine oxygen minimum zone. FEMS Microbiology Letters, 367, fnaa157 (2020)
Month Year : 2020-10-01
The unique geochemistry of Trans-Himalayan sulfur–borax hot springs facilitates high in-situ microbial diversity, while the local geodynamics drive the microbial flux through the hydrothermal system.
Exploration of the sulfur-boron spring system of Puga geothermal area (eastern Ladakh) revealed the peculiar, mesophiles-dominated microbiomes of these mineralogically special Trans-Himalayan hot springs which discharge boiling or near-boiling water having neutral pH, accompanied by low levels of sulfide, silicate and total dissolved solids, but high concentrations of sodium, boron, elemental sulfur and sulfate. The system’s distinctive geochemistry was propounded as the key facilitator of the high microbial diversity recorded, while the geological dynamics of this area, located just south of the tectonically-active Indus Tsangpo Suture Zone, was attributed as the main driver of microbial flux through the hydrothermal system. We found that snow-melts infiltrating (via tectonic faults) the ~160°C geothermal reservoir located within the breccia, at ~450 m depth, transport mesophilic microbes into the thermal waters; as these microorganisms emanate with the vent-water some remain alive, illustrating that natural bacterial populations are more heat-resilient than their laboratory counterparts.
Roy C et al, Microbiome and ecology of a hot spring-microbialite system on the Trans-Himalayan Plateau. Scientific Reports, 10, 5917 (2020)
Roy C et al, Geomicrobial dynamics of Trans-Himalayan sulfur–borax spring system reveals mesophilic bacteria’s resilience to high heat. Journal of Earth System Science, 129, 157 (2020)
Month Year : 2020-10-01
Study of jet-medium interaction in Pb-Pb collisions at LHC energies
we have studied possible modifications to inclusive jet yields and a set of
jet shape observables, namely, the fragmentation functions and radial momentum distributions when jets propagate through a deconfined partonic medium created in collisions of heavy nuclei at Large Hadron Collider (LHC) energies using a pQCD inspired model, Jet Evolution With Energy Loss (JEWEL). The observed modification of jet shape variables in Jewel corroborates the fact that in-medium fragmentation is harder and more collimated than the fragmentation in vacuum. We further observe that these modifications depend on the transverse momentum of jets and it seems that medium resolves the core structure of low momentum jets below 100 GeV/c at LHC energies.
Biswas et al. , Study of jet-medium interactions using jet shape observables in heavy ion collisions at LHC energies with JEWEL - J. Phys. G : Nucl. Part. Phys. 46 (2019) 095004
Month Year : 2019-08-01
A novel bacterial genus, Pradoshia, honouring late Dr Pradosh Roy, an eminent Bose Institute microbiologist, has been published recently
Researchers from North Bengal University, Bose Institute and Kalyani University have identified a new genus of bacteria the type strain of which can degrade the potent neurotoxin 3-nitropropionic acid (3-NPA) that has been responsible for several food-poisoning outbreaks. The researchers have named the novel genus Pradoshia eiseniae, as a tribute to their mentor late Dr. Pradosh Roy, an eminent Bose Institute microbiologist recognized for his pioneering contributions in the field of genetics and taxonomy of sulfur-oxidizing chemolithotrophic bacteria.
Saha T et al, Pradoshia eiseniae gen. nov., sp. nov., a spore-forming member
of the family Bacillaceae capable of assimilating 3-nitropropionic acid, isolated from the anterior gut of the earthworm Eisenia fetida. International Journal of Systematic and Evolutionary Microbiology, 69, 1265-1273 (2019)
Month Year : 2019-02-01
Topologically inspired walks on randomly connected landscapes with correlated fitness
Strictly adaptive walks on uncorrelated and correlated fitness landscapes have been a subject of intense research. However, some experimental findings tend to advance the notion of non-adaptive evolution in terms of epistasis. To address such evolutionary paths, herein we introduce the concept of topologically inspired walks on connected and correlated landscapes with complex topologies. These walks are dictated solely by the topology of connections and are not explicitly dependent on the underlying fitness values. In the biologically significant regime of sparse randomness, these topologically inspired walks might carry a population to a local optimum even faster than strictly adaptive walks. This effect becomes more pronounced with increasing correlations in fitness.
Kaur Grewal et al, Frontiers in Physics, 6, 138 (2018)
Month Year : 2018-12-01
Factors Controlling the Long-term (2009-2015) Trend of PM 2.5 and Black
Carbon Aerosols at Eastern Himalaya, India
Factors Controlling the Long-term (2009-2015) Trend of PM 2.5 and Black
Carbon Aerosols at Eastern Himalaya, India
Chirantan Sarkar, Arindam Roy, Abhijit Chatterjee, Sanjay K.
Ghosh, Sibaji Raha, STOTEN 29716
Month Year : 2018-11-01
GM2-synthase gene is regulated epigenetically at the level of transcription in renal cell carcinoma.
GM2-synthase produces sialic acid-containing glycosphingolipids called gangliosides, and its mRNA overexpression and the gangliosides it generates are linked to tumor progression, migration, and suppression of tumor-specific host immune responses. However, the mechanism underlying GM2-synthase de-repression in renal cell carcinoma (RCC) is poorly understood. Here, we demonstrate that higher GM2-synthase mRNA expression levels in various cancer cells and in human RCC tumors correlate with higher histone acetylation levels (H3K9, H3K14, or both) at region +38/+187 relative to the transcription start site (TSS) of the GM2-synthase gene than in normal kidney epithelial (NKE) cells or healthy adjacent tissues. An increase in GM2-synthase mRNA expression in cells treated with a histone deacetylase (HDAC) inhibitor was accompanied by increased histone acetylation levels at this promoter region. DNA methylation around the TSS was absent in both RCC cell lines and NKE cells. Of note, both the transcription factor Sp1 and corepressor HDAC1 associated with the +38/+187 region when the GM2-synthase gene was repressed in NKE and tumor-adjacent tissues, indicating plausible site-specific repressive roles of HDAC1 and Sp1 in GM2-synthase mRNA expression. Site-directed mutagenesis of the Sp1-binding site within the +38/+187 region relieved repressed luciferase activity of this region by limiting HDAC1 recruitment. Moreover, Sp1 or HDAC1 knockdown increased GM2-synthase transcription, and butyrate-mediated activation of GM2-synthase mRNA expression in SK-RC-45 cells was accompanied by Sp1 and HDAC1 loss from the +37/+187 region. Taken together, an epigenetic mechanism for the de-repression of the GM2-synthase gene in RCC has been identified.
Banerjee, A. et al., Elevated histone H3 acetylation and loss of the Sp1–HDAC1 complex de-repress the GM2-synthase gene in renal cell carcinoma. J. Biol. Chem., accepted for publication, Nov 2018.
Month Year : 2018-11-01
Transfer reactions with 7Be to study the cosmological Lithium problem
First approved project from India at HIE-ISOLDE, CERN. Experiment carried out successfully during November 16 - 21, 2018.
Month Year : 2018-11-01
miRTPred:A supervised ensemble approach for sensitive microRNA target prediction
miRTPred model is built by using experimentally validated miRNA-mRNA interactions from CLIP and CLASH. Thereafter, context features of the target binding site are generated from which the enriched features are selected. Finally several ensemble and non ensemble based models are trained, to select the optimal blended ensemble based predictor model with maximum predictive performance. It is available at http://bicresources.jcbose.ac.in/zhumur/mirtpred/
Maji RK et al, IEEE/ACM Trans Comput Biol Bioinform,doi: 10.1109/TCBB.2018.2858252(2018).
Month Year : 2018-07-01
Resonance states of weakly bound and unbound nuclei using supersymmetric quantum mechanics
The study of resonances in unstable/unbound nuclei are extremely important in connections with nuclear-astrophysics problems. With the increasing availability of exotic rare isotope beams at state of the art accelerators, researchers are encouraged to carry out studies on structure of such nuclei. To complement experimental findings about unstable/unbound nuclei, robust theoretical frameworks are lacking as there are substantial ambiguities in the results of theoretical calculations relevant to experimental findings. We decided to work on a theory which would be suitable particularly for unstable/unbound nuclei. We adopted the theoretical procedure of supersymmetric quantum mechanics for the first time to generate the resonance states and their wave functions for unstable/unbound nuclei with excellent results.
Resonance state wave functions of 15Be using supersymmetric
quantum mechanics
S. K. Dutta, D. Gupta, Swapan K. Saha
Phys. Lett. B 776, 464 (2018)
Study of resonance states of 11Be with isospectral bound state microscopic potential
S. K. Dutta, D. Gupta, D. Das and Swapan K. Saha
Jour. Phys. G: Nucl. Part. Phys. 41, 095104 (2014)
Month Year : 2018-01-01
We have developed a molecular marker in mulberry. The adoption of this marker-assisted selection technique will lead to predictive plant type of mulberry with tolerance to powdery mildew disease.
Chalcone synthase (CHS) is an essential enzyme in the phenylpropanoid pathway that catalyzes
the first step in flavonoid biosynthesis in plants under diverse environmental stress.
We have used CHS as a candidate gene in mulberry and developed Single Nucleotide Polymorphism
(SNP) based co-dominant Cleaved Amplified Polymorphic Sequence (CAPS)
marker associated with the CHS locus. The segregation pattern of the marker was studied
in an F1 population derived from a hybridization program between two mulberry genotypes
showing polymorphism for the CHS locus. Differential CHS activity of the recombinants has
been correlated with the segregation pattern of the marker. Homology modelling and docking
studies are performed for both the identified CHS alleles and correlated with respective
CHS activity. Phenotyping of Powdery Mildew infected F1 population indicated a probable
association with the CAPS marker.
Arora V et al, Allele specific CAPS marker development and characterization of chalcone synthase gene in Indian mulberry (Morus spp., family Moraceae). PLoS ONE 12(6): e0179189. https://doi.org/10.1371/journal.pone.0179189
Month Year : 2017-06-01
Measurement of angular variation of cosmic ray intensity with plastic scintillator detector
A new and simple technique has been developed using plastic scintillator detectors for the study of angular variation of cosmic ray intensity near the sea level. A systematic study of the characteristics of the plastic scintillator paddle detector has been carried out. The yield uniformity study of the paddle detector has been carried out. The angular variation of cosmic ray intensity is measured, in Kolkata, India during the beginning of 2017, with the coincidence technique and it is observed that the cosmic ray intensity decreases from ∼ 7 × 10^−3 to 3 × 10^−3 s^−1cm^−2sr^−1 corresponding to an increasing zenith angle of 0◦ to 70◦ respectively.
Roy S et al, Measurement of angular variation of cosmic ray intensity with plastic scintillator detector. Advanced Detectors for Nuclear, High Energy and Astroparticle Physics, Proceedings of ADNHEAP 2017, Springer Proceedings in Physics 201, 199-204, doi.org/10.1007/978 − 981 − 10 − 7665 − 7 20, ISBN 978-981-10-7664-0
Month Year : 2017-01-01
Some aspects of characterization of GEM detector
Basic Characterization of a triple-GEM detector has been carried out. Variation of gain over the active area of the detector has been checked, and the result shows a variation of ∼ 11.7 % over the area of 10 × 10 sq-cm. Tests have been done to check the dependance of gain on ambient relative humidity, and the results show that gain does not show any correlation with relative humidity.
Nag D et al, Some aspects of characterization of GEM detector. Advanced Detectors for Nuclear, High Energy and Astroparticle Physics, Proceedings of ADNHEAP 2017, Springer Proceedings in Physics 201, 205-210 (2017) doi.org/10.1007/978 − 981 − 10 − 7665 − 7 21, ISBN 978-981-10-7664-0
Month Year : 2017-01-01
Stability study of GEM detector measuring anode current
Triple Gas Electron Multiplier (GEM) detector prototype is built and tested with Argon and Carbon di-oxide gas mixture. The long-term stability study of this detector is performed using Fe55 X-ray source. The gain is measured and normalized for the T/p effect. In this measurement only a fluctuation about the mean value of 1.003 in the normalized gain is observed after T/p correction. No ageing is observed till an accumulation of charge per unit area greater than 12.0 mC per sq. mm. From these results it can be concluded that triple GEM detector can safely be used in high-energy physics experiments where a long-term stability of the detector is an essential criterion.
Adak R P et al, Long-term stability test of a triple GEM detector. Journal of Instrumentation, 11, T10001
Month Year : 2016-10-01
Mathematical modelling and experiments demonstrate that mycobacteriophages can kill mycobacteria by non-lytic mechanisms. The information derived could lead to the development of new drugs for the treatment of TB
Mycobacteriophages infect and grow in mycobacterium species, several of which happen to be dangerous pathogens – the best known example being Mycobacterium tuberculosis that causes the deadly disease tuberculosis. Eliminating tuberculosis through prevailing antibiotic-based strategies has had restricted success, due to the rise of drug-resistant strains. Phage therapy for tuberculosis is an interesting possibility. Sujoy Das Gupta (Microbiology) and Soumen Roy (Physics) are currently investigating the mechanism by which these phages interact with their mycobacterial hosts, thereby killing them. Using D29, as a model mycobacteriophage, they have found that in addition to lysis, this phage can induce cell death through an alternative mechanism involving production of superoxide radicals. By obtaining more insight into this intriguing phenomenon, they eventually hope to unravel novel metabolic pathways that can be targeted for drug development against tuberculosis. This work was also selected by the editors of AEM spotlight.
Reference: Samaddar S et al, Dynamics of mycobacteriophage-mycobacterial host interaction: Evidence for secondary mechanisms for host Lethality. Applied and Environmental Microbiology [ASM], 82, 124-133 (2016)
A new approach towards information retrieval from dynamic multidimensional images using complex networks developed. The method can be used for non-invasive diagnosis of dry eye disease
Soumen Roy presented a fresh and broad yet simple method of information retrieval from videos by converting them to time series and thence to networks. His lab used thermal imaging videos collected by collaborators at Calcutta University from patients at Calcutta Medical College. The mean pixel intensities from every frame of the imaged videos were collated into time series, which were then converted into networks. Using network measures they could successfully distinguish between dry eye patients and healthy individuals.
This approach is completely new in medical diagnostics, particularly in eye research. The findings are important because their technique is fast and non-invasive (requires no physical contact with affected organs). They also showed that their approach compares well to sophisticated image processing algorithms, which are much harder to implement at the level of real-time electronic devices. The technique can be applied to many other videos and might help in designing smart devices. A patent has also been filed by TIFAC (DST).
Reference: Banerjee SJ et al, Using complex networks towards information retrieval and diagnostics in multidimensional imaging. Scientific Reports [Nature], 5, 17271 (2015)
Mechanism of ganglioside GM2 mediated migration of tumor cells - a pivotal role of the integrin receptor
The definitive role of ganglioside GM2 in mediating tumor-induced growth and progression is still unknown. Kaushik Biswas recently reported a novel role of ganglioside GM2 in mediating tumor cell migration and uncovered its mechanism. They established the functional role of ganglioside GM2 by a multidirectional approach, using either silencing or over-expression of GM2-synthase, the key enzyme that controls GM2 biosynthesis. The mechanism of GM2-mediated tumor cell migration was elucidated using gene expression profiling as well as conventional biochemical techniques, which confirmed a role of integrin signaling and its downstream partners in the process. Finally, confocal microscopy suggested co-localization while co-immunoprecipitation and surface plasmon resonance confirmed direct interaction of membrane bound GM2 with the integrin receptor. Thus over-expression of select gangliosides (GM2) in tumors result in enhanced interaction with membrane bound integrin-1 causing activation of the downstream signaling leading to rearrangement of the actin cytoskeleton resulting in enhanced migration in tumor cells.
Reference: Kundu M et al, Mechanism of ganglioside GM2 mediated migration of tumor cells - a pivotal role of the integrin receptor. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research [Elsevier], 1863, 1472-89 (2016)
Key molecular regulators of early blight disease response in tomato have been revealed
In plants, for a steady, specific and sturdy response against an invading pathogen reprogramming in gene expression cascade is essential. This reprogramming initiates from transcriptional regulation of gene expression. However, the abundance of a transcript is also dependent on regulatory microRNAs that are targeting a specific mRNA. Thus, to gain insight into the response regulators in tomato plants infected with early blight disease pathogen Alternaria solani the whole transcriptome analysis was performed. The differentially expressed mRNAs, miRNAs, and the miRNA-mRNA interacting pairs were identified and in-depth bioinformatic analyses suggested that genes of plant-pathogen interaction, plant hormone signal transduction pathways and secondary metabolite biosynthesis were mostly affected by the regulated miRNAs. These analyses in the lab of Pallob Kundu have uncovered key regulators of Alternaria-stress response in tomato and would help in designing strategies for imparting resistance against the economically important pathogen.
Reference: Sarkar D et al, Integrated miRNA and mRNA expression profiling reveals the response regulators of a susceptible tomato cultivar to early blight disease. DNA Research [Oxford] dsx003 (2017)
delta factor of Bacillus subtilis is not a subunit of RNAP, but functions as a transcriptional factor
delta, a small protein found in most Gram-positive bacteria was, for a long time, thought to be a subunit of RNA polymerase and was shown to be involved in recycling of RNA polymerase at the end of each round of transcription. However, how delta participates in both up-regulation and down-regulation of genes in vivo remains unclear. Jayanta Mukhopadhyay has shown that in addition to the recycling of RNAP, Bacillus subtilis delta functions as a transcriptional activator by binding to an A-rich sequence located immediately upstream of the -35 element, consequently facilitating the open complex formation.
His group further showed that delta could also function as a transcriptional repressor in which the protein binds to an A-rich sequence located near the -35 element of the promoters and inhibits the open complex formation due to steric clash with sigma region 4.2. Thus, the results explain the mechanism of up-regulation and down-regulation of genes by the protein.
Reference: Prajapati RK et al, Bacillus subtilis delta factor functions as a transcriptional regulator by facilitating the open complex formation. Journal of Biological Chemistry [ASBMB], 291, 1064-75 (2016)
Newly designed mASAL, a lectin like Protein conferring sheath blight resistance in transgenic rice
Allium sativum leaf agglutinin (ASAL), a dimeric mannose binding lectin has been established earlier as potent insecticidal protein. Using site directed mutagenesis, a beta-turn was incorporated between 11th and 12th beta-strands of ASAL subunits, resulting in a stable monomeric variant, mASAL. Instead of being insecticidal, mASAL exhibits significant antifungal activity against Rhizoctonial solani, causes devastating sheath blight disease in rice. As per WHO/FAO recommendation, Pepsin digestion, thermal stability assay, targeted sera screening test and sensitization of Balb/c mice with mASAL established it as a biologically safe protein for biotechnological application. Transgenic indica rice expressing mASAL demonstrated significant tolerance to sheath blight. Studies conducted by Sampa Das’s group opens up the possibility of engineering important plants with mASAL for sustainable pathogen resistance.
Reference: Ghosh P et al, Monitoring the efficacy of mutated Allium sativum leaf lectin in transgenic rice against Rhizoctonial solani, BMC Biotechnology [BMC], 16, 24 (2016)
Critical roles of Hsp90 in CRAF kinase stabilization and actin dependent translocation to the plasma membrane during MAPK signaling
RAF isoforms are commonly regulated by several molecular events and scaffold proteins. Being a strong chaperone client, CRAF is always assisted by Hsp90. In this paper, we provide the explanation for the stringent assemblage between CRAF and Hsp90 that differs for both newly made and folded CRAF kinase. Atin Mandal observed that Hsp90 promotes CRAF denovo maturation, essential for CRAF stability and activity. However, after folding the stability of CRAF does not depend on Hsp90 anymore, although the association between Hsp90 and CRAF still remains intact. The post-folding interaction between Hsp90 and CRAF regulates actin-dependent translocation of the kinase during MAPK signaling. Thus, Hsp90 keeps CRAF kinase maturation and its intracellular translocation in balance to sustain accurate cellular growth and proliferation.
Reference: Mitra S et al, Bipartite Role of Heat Shock Protein (Hsp90) Keeps CRAF Kinase Poised for Activation. Journal of Biological Chemistry [ABSMB], 291, 24579-24593 (2016)
