Kumar GK (2016) Elife "Adapt or avoid."

Kumar GK

[Elife, 2016]

An enzyme called p38 MAP kinase helps nematodes to adapt to low-oxygen environments, and also to escape from them.

Kumar A et al. (2007) Curr Biol "Cell death: hook, line and linker."

Kumar A, Rothman JH

[Curr Biol, 2007]

The programmed death of particular cells in Caenorhabditis elegans and Drosophila has been shown to occur by non-apoptotic programs regulated by developmental timing. Such alternative programs may be used as a general mechanism to eliminate differentiated, functional cells.

Maurya, Ashish Kumar et al. (2022) MicroPubl Biol

Maurya, Ashish Kumar, Sengupta, Piali

[MicroPubl Biol, 2022]

The conserved CCRK, RCK, and CDKL5 kinases regulate cilia length in diverse organisms. In C. elegans , DYF-18 CCRK regulates DYF-5 RCK to shape both simple and complex cilia morphologies. The CDKL5 ortholog CDKL-1 has also been suggested to act downstream of DYF-18 but independently of DYF-5 to regulate lengths of simple rod-like cilia. Here we show that CDKL-1 is largely dispensable for regulation of complex cilia structures. Using genetic epistasis experiments, we confirm that CDKL-1 and DYF-5 act independently to control cilia architecture. Our results indicate that multiple kinases act via distinct pathways to regulate unique cilia ultrastructures.

Kumar S et al. (2012) Worm "Toward 959 nematode genomes."

Koutsovoulos G, Kumar S, Kaur G, Blaxter M

[Worm, 2012]

The sequencing of the complete genome of the nematode Caenorhabditis elegans was a landmark achievement and ushered in a new era of whole-organism, systems analyses of the biology of this powerful model organism. The success of the C. elegans genome sequencing project also inspired communities working on other organisms to approach genome sequencing of their species. The phylum Nematoda is rich and diverse and of interest to a wide range of research fields from basic biology through ecology and parasitic disease. For all these communities, it is now clear that access to genome scale data will be key to advancing understanding, and in the case of parasites, developing new ways to control or cure diseases. The advent of second-generation sequencing technologies, improvements in computing algorithms and infrastructure and growth in bioinformatics and genomics literacy is making the addition of genome sequencing to the research goals of any nematode research program a less daunting prospect. To inspire, promote and coordinate genomic sequencing across the diversity of the phylum, we have launched a community wiki and the 959 Nematode Genomes initiative (www.nematodegenomes.org/). Just as the deciphering of the developmental lineage of the 959 cells of the adult hermaphrodite C. elegans was the gateway to broad advances in biomedical science, we hope that a nematode phylogeny with (at least) 959 sequenced species will underpin further advances in understanding the origins of parasitism, the dynamics of genomic change and the adaptations that have made Nematoda one of the most successful animal phyla.

Kumar R et al. (2019) Biochimie "Characterization of Filarial Phosphoglycerate kinase."

Kumar R, Rathaur S, Ahmad F

[Biochimie, 2019]

Phosphoglycerate kinase (PGK) is a key enzyme of glycolysis which also acts as a mediator of DNA replication and repair in the nucleus. We have cloned and expressed PGK in Brugia malayi. The rBmPGK was found to be 415 amino acid residues long having 45kDa subunit molecular weight. This enzyme was also identified in different life stages of bovine filarial parasite Setaria cervi. The enzyme activity was highest in microfilarial stage followed by adult female and male as also shown by real time PCR in the present study. Further using BmPGK primers the cDNA prepared from S. cervi was amplified and sequenced which showed 100% homology with Brugia malayi PGK. B. malayi and S. cervi, PGK consists of conserved calmodulin binding domain (CaMBD) having 21 amino acids. In the present study we have shown the CaMBD binds to calcium-calmodulin and regulates its activity. The binding of calmodulin (CaM) with CaMBD was confirmed using calmodulin agarose binding pull down assay, which showed that the rBmPGK binds to CaM agarose-calcium dependent manner. The effect of CaM-Ca²⁺on the activity of rBmPGK was studied at different concentration of CaM (0.01-5.0 M) and calcium chloride (0.01-100 M). The rBmPGK was activated up to 85 % in the presence of CaM at 1 M and 10 M concentration of CaCl₂. Interestingly this activation was abrogated by metal chelator EDTA. Similar results were shown in case of Setaria cervi PGK. A significant increase (90+/-10) % in ScPGK activity was observed in the presence of CaM and CaCl₂ at 1.0 M and 1.0 mM respectively, further increase in the conc. of CaCl₂, the activity of ScPGK was found to be decreased like rBmPGK. Bioinformatics studies have also confirmed the interaction between CaMBD and CaM which showed CaM interacted to Phe 206, Gln 220, Arg 223 and Asn 224 of rBmPGK CaM binding domain. On the basis of these findings, it has been suggested that the activity of filarial PGK could be regulated in cells by Ca²⁺-CaM depending upon the concentration of calcium. To the best of our knowledge this is first report in filarial parasite.

Kumar A et al. (2002) J Biosci "Primary microcephaly: microcephalin and ASPM determine the size of the human brain."

Markandaya M, Kumar A, Girimaji SC

[J Biosci, 2002]

Kumar A et al. (2020) Cell Mol Life Sci "Caenorhabditis elegans: a model to understand host-microbe interactions."

Kumar A, Kalita MC, Baruah A, Tomioka M, Khan M, Iino Y

[Cell Mol Life Sci, 2020]

Host-microbe interactions within the gut are fundamental to all higher organisms. Caenorhabditis elegans has been in use as a surrogate model to understand the conserved mechanisms in host-microbe interactions. Morphological and functional similarities of C. elegans gut with the human have allowed the mechanistic investigation of gut microbes and their effects on metabolism, development, reproduction, behavior, pathogenesis, immune responses and lifespan. Recent reports suggest their suitability for functional investigations of human gut bacteria, such as gut microbiota of healthy and diseased individuals. Our knowledge on the gut microbial diversity of C. elegans in their natural environment and the effect of host genetics on their core gut microbiota is important. Caenorhabditis elegans, as a model, is continuously bridging the gap in our understanding the role of genetics, environment, and dietary factors on physiology of the host.

Kumar N et al. (1991) International C. elegans Meeting "CLASSICAL CONDITIONING IN C. ELEGANS;"

van der Kooy D, Wen JYM, Culotti JG, Kumar N

[International C. elegans Meeting, 1991]

The nematode is an excellent model system in which to pursue a neurogenetic analysis of behavior. In particular, we chose to train nematodes in a classical conditioning paradigm in order to focus on the cellular and molecular bases of learning and memory. Initially, 2 chemotactically attractive ions Na+ (NaCH3COO) and Cl- (NH4Cl) were chosen as conditioned stimuli (CSs) and E. coli, a rewarding food source, was used as the unconditioned stimuli (US). The animals were trained by exposing them to a constant concentration of one ion (CS+) paired with the US followed by exposure to the other ion (CS-) in the absence of the US. The experiment was counterbalanced for which CS was paired with the US and for the order of CS presentation. The testing consisted of placing approximately 100 of the trained animals between point gradients of each CS (in the absence of the US) and allowing them to migrate towards one of the gradient centers. CS levels were balanced such that naive animals displayed equal chemotactic preferences for either CS. Immediately after one CS+ and one CS- pairing, 67.1_3.1% of the animals demonstrated a preference for the CS paired with the US. A 5 hour food deprivation prior to training increased the preference for the CS+ ion to 77.3_2.6%. These animals showed evidence of memory for the association at 7 hours post-training but by 27 hours post-training their test performance was no longer significantly different (56.5+9.8 %) from controls. The nematodes learned inhibitory relationships (the CS- predicts the absence of food) as well as excitatory ones (the CS+ predicts the presence of food). We have also been able to demonstrate conditioned aversion learning by replacing E. coli, an appetitive US, with an aversive garlic extract. In this case nematodes can be trained to avoid the CS+ ion. In addition to being sensitive to changes in the US, the nematode can also learn about different CSs. If distinct temperatures are used as CSs instead of ions, food deprived nematodes learn to exhibit a preference for the temperature that was paired with the food reward. Thus, a desirable range of conditioned stimuli and conditioning responses can be utilized in learning paradigms with C. elegans. Presently we are undertaking a mutational screen for learning and memory mutants.

Kumar S et al. (2023) Biotechnol Appl Biochem "Antimicrobial effect of pimozide by targeting ROS-mediated killing in Staphylococcus aureus."

Sandeep K, Kumar A, Kumar S, Kumar R

[Biotechnol Appl Biochem, 2023]

In spite of the higher nosocomial and community-acquired infections acquired by Staphylococcus aureus, emerging drug resistance is a leading cause of increased mortality and morbidity associated with the overuse of antimicrobials. It is an emergent need to find out new molecules to combat such infections. In the present study, we analyzed the antibacterial effect of pimozide (PMZ) against Gram +ve and Gram -ve bacterial strains including methicillin-sensitive (MSSA) and methicillin resistance (MRSA) S. aureus. The growth of MSSA and MRSA was completely inhibited at concentrations of 12.5 μg/ml and 100 μg/ml, respectively which is referred to as 1x MIC. The cell viability was completely eliminated within 90 min of PMZ treatment (2x MIC) through ROS-mediated killing without affecting cell membrane permeability. It suppressed α-hemolysin biofilm formation of different S. aureus strains by almost 50% at 1x MIC concentration and was found to detach matured biofilm. PMZ treatment effectively eliminates S. aureus infection in C. elegans and improves its survival by 90% and found safe to use with no hemolytic effect on human and chicken blood tissues. Taken together, it is concluded that PMZ may turn out to be an effective antibacterial for treating bacterial infections including MSSA and MRSA. This article is protected by copyright. All rights reserved.

Kumar A et al. (2014) Nat Protoc "Dual-view plane illumination microscopy for rapid and spatially isotropic imaging."

Gandler W, Colon-Ramos DA, Christensen R, Chandris P, Bokinsky A, Rondeau G, Bao Z, McCreedy E, Kumar A, McAuliffe M, Shroff H, Wu Y

[Nat Protoc, 2014]

We describe the construction and use of a compact dual-view inverted selective plane illumination microscope (diSPIM) for time-lapse volumetric (4D) imaging of living samples at subcellular resolution. Our protocol enables a biologist with some prior microscopy experience to assemble a diSPIM from commercially available parts, to align optics and test system performance, to prepare samples, and to control hardware and data processing with our software. Unlike existing light sheet microscopy protocols, our method does not require the sample to be embedded in agarose; instead, samples are prepared conventionally on glass coverslips. Tissue culture cells and Caenorhabditis elegans embryos are used as examples in this protocol; successful implementation of the protocol results in isotropic resolution and acquisition speeds up to several volumes per s on these samples. Assembling and verifying diSPIM performance takes 6 d, sample preparation and data acquisition take up to 5 d and postprocessing takes 3-8 h, depending on the size of the data.