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Dey, N.

Publications and source records attributed to Dey, N..

5 recordsLinked to original sources

Combinatorial phenotypic landscape enables bacterial resistance to phage infection

AbstractSuccess of phage therapies is limited by bacterial defenses against phages. While a large variety of anti- phage defense mechanisms has been characterized, how expression of these systems is distributed across individual cells and how their combined activities translate into protection from phages has not been studied. Using bacterial single-cell RNA sequencing, we profiled the transcriptomes of [~]50,000 cells from cultures of a human pathobiont, Bacteroides fragilis, infected with a lytic bacteriophage. We quantified the asynchronous progression of phage infection in single bacterial cells and reconstructed the infection timeline, characterizing both host and phage transcriptomic changes as infection unfolded. We discovered a subpopulation of bacteria that remained uninfected and determined the heterogeneously expressed host factors associated with protection. Each cells vulnerability to phage infection was defined by combinatorial phase-variable expression of multiple genetic loci, including capsular polysaccharide (CPS) biosynthesis pathways, restriction-modification systems (RM), and a previously uncharacterized operon likely encoding fimbrial genes. By acting together, these heterogeneously expressed phase-variable systems and anti-phage defense mechanisms create a phenotypic landscape where distinct protective combinations enable the survival and re-growth of bacteria expressing these phenotypes without acquiring additional mutations. The emerging model of complementary action of multiple protective mechanisms heterogeneously expressed across an isogenic bacterial population showcases the potent role of phase variation and stochasticity in bacterial anti-phage defenses. One Sentence SummaryCombinatorial phenotypic states with differential vulnerability to phage infection across a Bacteroides fragilis population enable a small number of super-resistant bacterial cells to evade the phage without the need for acquiring mutations.

systems biology↗

Interruption of glucagon signaling augments islet non-alpha cell proliferation in SLC7A2- and mTOR-dependent manners

ObjectiveDysregulated glucagon secretion and inadequate functional beta cell mass are hallmark features of diabetes. While glucagon receptor (GCGR) antagonism ameliorates hyperglycemia and elicits beta cell regeneration in pre-clinical models of diabetes, it also promotes alpha and delta cell hyperplasia. We sought to investigate the mechanism by which loss of glucagon action impacts pancreatic islet non-alpha cells, and the relevance of these observations in a human islet context. MethodsWe used zebrafish, rodents, and transplanted human islets comprising six different models of interrupted glucagon signaling to examine their impact on delta and beta cell proliferation and mass. We also used models with global deficiency of the cationic amino acid transporter, SLC7A2, and mTORC1 inhibition via rapamycin, to determine whether amino acid-dependent nutrient sensing was required for islet non-alpha cell growth. ResultsInhibition of glucagon signaling stimulated delta cell proliferation in mouse and transplanted human islets, and in mouse islets. This was rapamycin-sensitive and required SLC7A2. Likewise, gcgr deficiency augmented beta cell proliferation via SLC7A2- and mTORC1-dependent mechanisms in zebrafish and promoted cell cycle engagement in rodent beta cells but was insufficient to drive a significant increase in beta cell mass in mice. ConclusionOur findings demonstrate that interruption of glucagon signaling augments islet non-alpha cell proliferation in zebrafish, rodents, and transplanted human islets in a manner requiring SLC7A2 and mTORC1 activation. An increase in delta cell mass may be leveraged for future beta cell regeneration therapies relying upon delta cell reprogramming.

cell biology↗

Genome-wide Identification of the Laccase Gene Family in White Jute (Corchorus capsularis): Potential Targets for Lignin Engineering in Bast Fiber

Jute (Corchorus spp.) is an important industrial bast fibre crop valued for its lignocellulosic fibres, yet the molecular basis of fibre lignification remains unexplored. Laccase (EC 1.10.3.2) is a key enzyme catalysing the final steps of lignin polymerisation. A genome-wide analysis of white jute (Corchorus capsularis) identified 32 putative laccase genes (CcaLACs) that were phylogenetically grouped into six clades. Expression profiling revealed predominant expression in phloem tissue (16 genes), followed by leaf (8) and xylem/root tissues (4). Several CcaLACs showed progressive upregulation from early growth to harvest stages. Homology with Arabidopsis laccases highlighted candidate genes involved in lignification, which were further supported by transcriptomic and qRT-PCR analyses. Notably, key CcaLACs showed significantly reduced expression in dlpf (deficient lignified phloem fibre), a low-lignin white jute mutant. CcaLAC expression was also responsive to abiotic stresses, including abscisic acid and copper. MicroRNA target prediction identified Ath-miR397a and Ath-miR397b as potential regulators of multiple CcaLACs. Structural and subcellular analyses revealed conserved motifs, transmembrane domains, and diverse cellular localisation. Gene ontology analysis linked CcaLACs to lignin and phenylpropanoid biosynthesis. Among them, CcaLAC28 and CcaLAC32 emerged as strong candidate genes associated with phloem fibre lignification, representing promising targets for future functional validation towards developing low-lignin jute varieties.

plant biology↗

Whole genome assembly of the Little Millet (Panicum sumatrense) genome: A climate resilient crop species

Little millet (Panicum sumatrense) belongs to one of the largest genera, Panicum comprising of 500 species that are distributed especially in tropical and sub-tropical Asia as well as Africa. This is a climate resilient crop that has the ability to adapt to adverse growing conditions, especially drought. Added to this is the better nutritional profile of little millet, which has higher iron and fibre contents as compared with rice. These characteristics make it an important crop species that would be pivotal for ensuring food security. Generating genomic resources for the species is significant and will have implications in crop improvement. Therefore, in the present study we report the de novo whole genome sequence of P. sumatrense. Long read sequencing and Hi-C based scaffolding resulted in a total of 279 scaffolds with N50 of 7.8Mb. The genome was annotated to predict protein coding genes and orthologous groups were analysed after comparison with various plant genomes. This high-quality genome assembly can be a valuable resource as future reference for genomic studies in this crop and related crop species.

genomics↗

De novo assembly of the whole genome of Moth bean (Vigna aconitifolia), an underutilized Vigna species of India

As a fast-growing legume species, moth bean (Vigna aconitifolia) has a unique habit of sustaining in conditions of higher temperatures and drought. This grain legume is also valued for it seeds which have one of the highest contents of proteins amongst all grain legumes. This plant can be a rich source of genomic resources, which can be applied to improve abiotic stress response in allied grain legumes and also help understand the biological processes governing their overall development. Here we generate a de novo genome assembly of Vigna aconitifolia using PacBio High-Fidelity reads and Hi-C sequencing data, with a total size of 409 Mb and contig N50 of more than 30Mb. We also annotated the genome for repeat sequences, found that the moth bean genome comprises of about 54% of repetitive sequences, and predicted 36950 protein-coding genes. Using the available RNA-Seq data for moth bean, we have developed a differential expression profile for various tissues of moth bean using the whole genome as a reference and identified simple sequence repeats that could be developed into viable molecular markers. This nascent study will provide insight into the identification of agronomically important genes and accelerate the genetic improvement of moth bean as well as other legume crops.

genomics↗