Biology subjects

Kulkarni, S. R.

Publications and source records attributed to Kulkarni, S. R..

6 recordsLinked to original sources

bioRxiv2024

Metagenomics to Metabolomics: Integrating Genomic Insights for Mulberry Crop Protection and Enhancement

Indian Mulberry (Morus indica) is vital in sericulture, with their leaves serving as the primary food source for silkworms. The soil microbiome surrounding mulberry trees plays a pivotal role in nutrient cycling and ecosystem functioning. This study utilizes metagenomic analysis to explore the taxonomic diversity and functional potential of microbial communities in mulberry soil, particularly focusing on the rhizosphere. Key bacterial species such as Pseudomonas, Frankia, Azosipirulum are identified, highlighting their importance in mulberry health and disease dynamics. The abundance distribution of these bacterial populations reveals significant trends, offering insights into mulberry agroecosystem microbial ecology. Understanding garden soil-derived microbial consortia provides a foundation for exploring their role in nutrient cycling and plant health. The study reveals the intricate web of interactions between mulberry and their surrounding soil microbiota and identification of metabolites. Leveraging high-throughput sequencing and bioinformatics, the research identifies potential metabolites as biofertilizers and biopesticides, aiming to improve agricultural sustainability. The findings underscore the critical role of soil microbes in maintaining soil fertility, supporting plant health, and enhancing ecosystem resilience. Despite limitations and gaps, the study contributes to advancing eco-friendly agricultural practices and promoting soil health in mulberry cultivation. Ultimately, the research transcends the laboratory, resonating with stakeholders as it unravels the genetic blueprints of soil life and sows seeds of sustainable progress.

genomics↗

bioRxiv2022

Lung endothelium instructs dormancy of susceptible metastatic tumour cells

During metastasis, cancer cells hijack blood vessels and travel via the circulation to colonize distant sites1,2. Due to the rarity of these events, the immediate cell fate decisions of arrested circulating tumour cells (aCTC) are poorly understood and the role of the endothelium, as the interface of dissemination, remains elusive3,4. Here, we developed a novel strategy to specifically enrich for aCTC subpopulations capturing all cell states of the extravasation process and, in combination with single cell RNA-sequencing, provide a first blueprint of the transcriptional basis of early aCTC decisions. Upon their arrest at the metastatic site, tumour cells either started proliferating intravascularly or extravasated and preferably reached a state of quiescence. Endothelial-derived angiocrine Wnt factors were found to drive this bifurcation by inducing a mesenchymal-like phenotype in aCTCs instructing them to follow the extravasation-dormancy branch. Surprisingly, homogenous tumour cell pools showed an unexpected baseline heterogeneity in Wnt signalling activity and epithelial-to-mesenchyme-transition (EMT) states. This heterogeneity was established at the epigenetic level and served as the driving force of aCTC behaviour. Hypomethylation enabled high baseline Wnt and EMT activity in tumour cells leading them to preferably follow the extravasation-dormancy route, whereas methylated tumour cells had low activity and proliferated intravascularly. The data identify the pre-determined methylation status of disseminated tumour cells as a key regulator of aCTC behaviour in the metastatic niche. While metastatic niche-derived factors per default instruct the acquisition of quiescence, aCTCs unwind a default proliferation program and only deviate from it if hypomethylation in key gene families renders them responsive towards the microenvironment.

cancer biology↗

bioRxiv2020

Assessment of heterotic potential and combining ability of immortal restorer lines derived from an elite rice hybrid, KRH-2, for the development of superior rice hybrids

Present investigation was carried out to assess the heterotic potential and combining ability of immortal restorer lines [consisting of two recombinant inbred lines (RILs) and two doubled haploid lines (DHLs)] developed from an elite rice hybrid, KRH-2 by crossing them with three popular WA-CMS lines, IR58025A, CRMS32A and APMS6A through line x tester analysis. The doubled haploid line 1 (DHL-1) was observed to be a good general combiner for total grain yield per plant (YLD) and other yield component traits and among the CMS lines, IR58025A was observed to be the best combiner as it showed positive significant values for the traits viz., total grain yield per plant, panicle length and spikelet fertility. Higher preponderance of the variance associated with specific combining ability (SCA) as compared to general combining ability (GCA) variance was observed for most of the traits indicated the predominant role of non-additive gene action in the expression of the traits. Out of twelve novel crosses between the immortal restorer lines derived from KRH-2 and the WA-CMS lines, 66.66% (eight crosses) showed significant and desirable SCA effects for the traits viz., total grain yield per plant, days to fifty percent flowering, plant height, flag leaf length, flag leaf width, number of filled grains per panicle and spikelet fertility. Two crosses IR58025A/RIL-24 and CRMS32A/RIL-24 were observed to be the most promising cross combinations showing standard heterosis of >50% for YLD trait (as compared with KRH-2) with higher prevalence of GCA and SCA, respectively. Heterotic yield advantage of IR58025A/RIL-24 and CRMS32A/RIL-24 was 77.05% and 54.74%, respectively over KRH-2 and these can be utilized for developing commercial hybrids. The present study also indicates the potentiality of RILs in providing useful parental lines for developing heterotic hybrids which are hard to get from outside sources in the new intellectual property regime.

genetics↗

bioRxiv2020

Deglutarylation of GCDH by SIRT5 controls lysine metabolism in mice

ABSTRACTA wide range of protein acyl modifications has been identified on enzymes across various metabolic processes; however, the impact of these modifications remains poorly understood. Protein glutarylation is a recently identified modification that can be non-enzymatically driven by glutaryl-CoA. In mammalian systems, this unique metabolite is only produced in the lysine and tryptophan oxidative pathways. To better understand the biology of protein glutarylation, we studied the relationship between enzymes within the lysine/tryptophan catabolic pathways, protein glutarylation, and regulation by the deglutarylating enzyme Sirtuin 5 (SIRT5). Here, we identify glutarylation on the lysine oxidation pathway enzyme glutaryl-CoA dehydrogenase (GCDH). We show increased GCDH glutarylation when glutaryl-CoA production is stimulated by lysine catabolism. Our data reveal glutarylation of GCDH impacts its function, ultimately decreasing lysine oxidation. We then demonstrate the ability of SIRT5 to deglutarylate GCDH, restoring its enzymatic activity. Finally, metabolomic and bioinformatic analyses indicate an expanded role for SIRT5 in regulating amino acid metabolism. Together, these data support a model whereby a feedback loop exists within the lysine/tryptophan oxidation pathway, in which glutaryl-CoA is produced, in turn inhibiting GCDH function via glutaryl modification of GCDH lysine residues, and can be relieved by SIRT5 deacylation activity.View Full Text

biochemistry↗

bioRxiv2019

Enhanced TF binding site maps improve regulatory networks learned from accessible chromatin data

Determining where transcription factors (TF) bind in genomes provides insights into which transcriptional programs are active across organs, tissue types, and environmental conditions. Recent advances in high-throughput profiling of regulatory DNA have yielded large amounts of information about chromatin accessibility. Interpreting the functional significance of these datasets requires knowledge of which regulators are likely to bind these regions. This can be achieved by using information about TF binding preferences, or motifs, to identify TF binding events that are likely to be functional. Although different approaches exist to map motifs to DNA sequences, a systematic evaluation of these tools in plants is missing. Here we compare four motif mapping tools widely used in the Arabidopsis research community and evaluate their performance using chromatin immunoprecipitation datasets for 40 TFs. Downstream gene regulatory network (GRN) reconstruction was found to be sensitive to the motif mapper used. We further show that the low recall of FIMO, one of the most frequently used motif mapping tools, can be overcome by using an Ensemble approach, which combines results from different mapping tools. Several examples are provided demonstrating how the Ensemble approach extends our view on transcriptional control for TFs active in different biological processes. Finally, a new protocol is presented to efficiently derive more complete cell type-specific GRNs through the integrative analysis of open chromatin regions, known binding site information, and expression datasets.

bioinformatics↗

bioRxiv2017

TF2Network: predicting transcription factor regulators and gene regulatory networks in Arabidopsis using publicly available binding site information

A gene regulatory network (GRN) is a collection of regulatory interactions between transcription factors (TFs) and their target genes. GRNs control different biological processes and have been instrumental to understand the organization and complexity of gene regulation. Although various experimental methods have been used to map GRNs in Arabidopsis thaliana, their limited throughput combined with the large number of TFs makes that for many genes our knowledge about regulating TFs is incomplete. We introduce TF2Network, a tool that exploits the vast amount of TF binding site information and enables the delineation of GRNs by detecting potential regulators for a set of co-expressed or functionally related genes. Validation using two experimental benchmarks reveals that TF2Network predicts the correct regulator in 75-92% of the test sets. Furthermore, our tool is robust to noise in the input gene sets, has a low false discovery rate, and shows a better performance to recover correct regulators compared to other plant tools. TF2Network is accessible through a web interface where GRNs are interactively visualized and annotated with various types of experimental functional information. TF2Network was used to perform systematic functional and regulatory gene annotations, identifying new TFs involved in circadian rhythm and stress response.

bioinformatics↗