Department of Bioscience & Bioengineering

&ldquo;IIT Jodhpur is committed to impart quality education to facilitate the creation of qualified, competent and responsible human resources to meet the emerging technological challenges of the world. It is working towards creating an equitable learning platform that is positive, accessible and effective in the face of the modern societal and scientific advancements.

Flexibility in curriculum, in all its academic programs, encompassing elements of teaching, research, creativity, innovation and entrepreneurship is the most unique feature of IIT Jodhpur. The Department of Science and Technology (DST), under the National Mission on Cyber Physical Systems, has identified IIT Jodhpur as a Technology &amp; Innovation Hub in the area of Augmented Reality and Virtual Reality. The institute has also been nominated as the coordinator for the Jodhpur City and Knowledge Cluster by the Office of Principal Scientific Adviser, Government of India.

The sprawling 852-acre IIT Jodhpur campus is a majestic tribute to the deep-rooted diverse cultural heritage of the region. The campus is an architectural masterpiece, which is slated to become an international exemplar of sustainability with net-zero energy, and advanced water and waste management strategies.&rdquo;

IIT Jodhpur

Cowpea is sensitive to drought and heat stress, particularly at the reproductive stages of development. Both stresses limit growth and yield, and their effect is more devastating when occurring concurrently. Dehydration-responsive element-binding protein 2A (DREB2A) is an important signaling hub integrating information about two different abiotic stresses, drought and heat. We identified VuDREB2A as a canonical DREB ortholog in cowpea, activating downstream stress-responsive genes by binding to DREs in their promoter. Post-translational modification of a negative regulatory domain (NRD) within the VuDREB2A protein prevents its degradation. Targeted deletion of the NRD produces a stable and constitutively active form VuDREB2A-CA. However, there is very little evidence of its practical utility under field conditions. This study overexpressed the VuDREB2A-CA in a popular cowpea variety and conducted drought- and heat-tolerance experiments across various stress regimes. Transgenic cowpea exhibited significant tolerance with consistently higher yield when exposed to over 30-d drought stress and 3-d exposure to high temperature (28&nbsp;°C˗52&nbsp;°C) without any pleiotropic alterations. The transgenic lines showed higher <a href="https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/photosynthetic-efficiency">photosynthetic efficiency</a>, <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/plant-osmotic-adjustment">osmotic adjustment</a>, antioxidant defense, <a href="https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/critical-thermal-maximum">thermotolerance</a>, and significantly higher survival and increased biomass than the wild type. Late <a href="https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/embryogenesis">embryogenesis</a> abundant 5, <a href="https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/heat-shock-protein-70">heat shock protein 70</a>, <a href="https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/dehydrin">dehydrin</a>, mitogen-activated protein kinase 2/4, <a href="https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/isoflavonoid">isoflavonoid</a> <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/reductase">reductase</a>, and myoinositol phosphate <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/synthase">synthase</a> were upregulated in transgenic lines under drought and heat stress. Through <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/gene-expression-profiling">transcriptome analysis</a> of the transgenic lines, we found significant up-regulation of various stress-responsive cowpea genes, having DRE in their promoter. Our results suggest that overexpression of VuDREB2A could improve cowpea production under drought and high temperatures.

World University root node

Plant Physiology and Biochemistry

Enhanced osmotic adjustment, antioxidant defense, and photosynthesis efficiency under drought and heat stress of transgenic cowpea overexpressing an engineered DREB transcription factor

Recurrent spells of droughts are more common than a single drought, with intermittent moist recovery intervals. While the detrimental effects of the first drought on plant structure and physiology are unavoidable, if survived, plants can memorize the first drought to present a more robust response to the following droughts. This includes a partial stomatal opening in the watered recovery interval, higher levels of osmoprotectants and ABA, and attenuation of photosynthesis in the subsequent exposure. Short-term drought memory is regulated by ABA and other phytohormone signaling with transcriptional memory behavior in various genes. High levels of methylated histones are deposited at the drought-tolerance genes. During the recovery interval, the RNA polymerase is stalled to be activated by a pause-breaking factor in the subsequent drought. Drought leads to DNA demethylation near drought-response genes, with genetic control of the process. Progenies of the drought-exposed plants can better adapt to drought owing to the inheritance of particular methylation patterns. However, a prolonged watered recovery interval leads to loss of drought memory, mediated by certain demethylases and chromatin accessibility factors. Small RNAs act as critical regulators of drought memory by altering transcript levels of drought-responsive target genes. Further studies in the future will throw more light on the genetic control of drought memory and the interplay of genetic and epigenetic factors in its inheritance. Plants from extreme environments can give queues to understanding robust memory responses at the ecosystem level.

Planta

How do plants remember drought?

The role of commensal bacterial microbiota in the pathogenesis of human malignancies has been a research field of incomparable progress in recent years. Although breast tissue is commonly assumed to be sterile, recent studies suggest that human breast tissue may contain a bacterial microbiota. In this study, we used an immune-competent orthotopic breast cancer mouse model to explore the existence of a unique and independent bacterial microbiota in breast tumors. We observed some similarities in breast cancer microbiota with skin; however, breast tumor microbiota was mainly enriched with Gram-negative bacteria, serving as a primary source of lipopolysaccharide (LPS). In addition, dextran sulfate sodium (DSS) treatment in late-stage tumor lesions increased LPS levels in the breast tissue environment. We also discovered an increased expression of S100A7 and low level of TLR4 in late-stage tumors with or without DSS as compared to early-stage tumor lesions. The treatment of breast cancer cells with LPS increased the expression of S100A7 in breast cancer cells in vitro. Furthermore, S100A7 overexpression downregulated TLR4 and upregulated RAGE expression in breast cancer cells. Analysis of human breast cancer samples also highlighted the inverse correlation between S100A7 and TLR4 expression. Overall, these findings suggest that the commensal microbiota of breast tissue may enhance breast tumor burden through a novel LPS/S100A7/TLR4/RAGE signaling axis. © 2021 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

Molecular oncology

Lipopolysaccharide from the commensal microbiota of the breast enhances cancer growth: role of S100A7 and TLR4

Chemotherapy forms the backbone of current treatments for many patients with advanced non-small-cell lung cancer (NSCLC). However, the survival rate is low in these patients due to the development of drug resistance, including cisplatin resistance. In this study, we developed a novel strategy to combat the growth of cisplatin-resistant (CR) NSCLC cells. We have shown that treatment with the plant-derived, non-psychotropic small molecular weight molecule, cannabidiol (CBD), significantly induced apoptosis of CR NSCLC cells. In addition, CBD treatment significantly reduced tumor progression and metastasis in a mouse xenograft model and suppressed cancer stem cell properties. Further mechanistic studies demonstrated the ability of CBD to inhibit the growth of CR cell lines by reducing NRF-2 and enhancing the generation of reactive oxygen species (ROS). Moreover, we show that CBD acts through Transient Receptor Potential Vanilloid-2 (TRPV2) to induce apoptosis, where TRPV2 is expressed on human lung adenocarcinoma tumors. High expression of TRPV2 correlates with better overall survival of lung cancer patients. Our findings identify CBD as a novel therapeutic agent targeting TRPV2 to inhibit the growth and metastasis of this aggressive cisplatin-resistant phenotype in NSCLC. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Cancers

Cannabidiol inhibits tumorigenesis in cisplatin-resistant non-small cell lung cancer via TRPV2

Background: Molecular mechanisms underlying inflammation-associated breast tumor growth are poorly studied. S100A7, a pro-inflammatory molecule has been shown to enhance breast cancer growth and metastasis. However, the S100A7-mediated molecular mechanisms in enhancing tumor growth and metastasis are unclear. Methods: Human breast cancer tissue and plasma samples were used to analyze the expression of S100A7, cPLA2, and PGE2. S100A7-overexpressing or downregulated human metastatic breast cancer cells were used to evaluate the S100A7-mediated downstream signaling mechanisms. Bi-transgenic mS100a7a15 overexpression, TNBC C3 (1)/Tag transgenic, and humanized patient-derived xenograft mouse models and cPLA2 inhibitor (AACOCF3) were used to investigate the role of S100A7/cPLA2/PGE2 signaling in tumor growth and metastasis. Additionally, CODEX, a highly advanced multiplexed imaging was employed to delineate the effects of S100A7/cPLA2 inhibition on the recruitment of various immune cells. Results: In this study, we found that S100A7 and cPLA2 are highly expressed and correlate with decreased overall survival in breast cancer patients. Further mechanistic studies revealed that S100A7/RAGE signaling promotes the expression of cPLA2 to mediate its oncogenic effects. Pharmacological inhibition of cPLA2 suppressed S100A7-mediated tumor growth and metastasis in multiple pre-clinical models including transgenic and humanized patient-derived xenograft (PDX) mouse models. The attenuation of cPLA2 signaling reduced S100A7-mediated recruitment of immune-suppressive myeloid cells in the tumor microenvironment (TME). Interestingly, we discovered that the S100A7/cPLA2 axis enhances the immunosuppressive microenvironment by increasing prostaglandin E2 (PGE2). Furthermore, CO-Detection by indEXing (CODEX) imaging-based analyses revealed that cPLA2 inhibition increased the infiltration of activated and proliferating CD4+ and CD8+ T cells in the TME. In addition, CD163+ tumor associated-macrophages were positively associated with S100A7 and cPLA2 expression in malignant breast cancer patients. Conclusions: Our study provides new mechanistic insights on the cross-talk between S100A7/cPLA2 in enhancing breast tumor growth and metastasis by generating an immunosuppressive TME that inhibits the infiltration of cytotoxic T cells. Furthermore, our studies indicate that S100A7/cPLA2 could be used as novel prognostic marker and cPLA2 inhibitors as promising drugs against S100A7-overexpressing aggressive breast cancer. © 2022, The Author(s).

Journal of Experimental \& Clinical Cancer Research

cPLA2 blockade attenuates S100A7-mediated breast tumorigenicity by inhibiting the immunosuppressive tumor microenvironment

Frontiers in Cell and Developmental Biology

Inflammation and Myeloid Cells in Cancer Progression and Metastasis

MicroRNAs (miRNAs) are small, non-coding RNAs, 18–25 nt in length, that play a crucial role in regulating genes associated with the physiological processes and responses to various biotic and abiotic stresses. Different conserved and species-specific microRNAs and their functions have been identified, primarily in plants such as rice and Arabidopsis with sequenced genomes. Our present study identifies drought-responsive miRNAs and their potential targets from mungbean under three days of drought stress induced by PEG-6000. We constructed small RNA libraries from both control and drought-treated tolerant and susceptible mungbean genotypes and identified various miRNAs involved in drought stress regulation. Analysis of differentially expressed genes (DEGs) revealed 79 up-regulated and 158 down-regulated novel miRNAs and two up-and down-regulated known miRNAs under drought. Annotation of the miRNAs followed by target prediction and expression analysis revealed five miRNAs, Vra-miR160, Vra-miR164, Vra-miR167, Vra-miR394, and Vra-miR398, were potentially involved in the regulation of drought-responsive genes. Their predicted target genes were an Auxin response factor (ARF), a NAC (for petunia NAM and Arabidopsis ATAF1, ATAF2, and CUC2) transcription factor, Serine acetyltransferase 1, and Multicopper oxidase LPR2-like. The expression of drought-responsive miRNAs and their targets were validated by real-time PCR. Our data suggest that various known and novel microRNAs activated transcription factors, enzyme kinases, and hormone signaling pathways alleviate drought stress in the tolerant K-851 genotype of mungbean. © 2022 The Authors

Current Plant Biology

Identification of differentially expressed mungbean miRNAs and their targets in response to drought stress by small RNA deep sequencing

Environmental Technology and Innovation

Superiority of activated graphite/CuO composite electrode over Platinum based electrodes as cathode in algae assisted microbial fuel cell

An accurate understanding of biomolecular mechanisms and diseases requires information on protein qua-ternary structure (QS). A critical challenge in inferring QS information from crystallography data is distinguishing biological interfaces from fortuitous crystal-packing contacts. Here, we employ QS conservation across homologs to infer the biological relevance of hetero-oligomers. We compare the structures and compositions of hetero-oligomers, which allow us to annotate 7,810 complexes as physiologically relevant, 1,060 as likely errors, and 1,432 with comparative information on subunit stoichiometry and composition. Excluding immuno-globulins, these annotations encompass over 51% of hetero-oligomers in the PDB. We curate a dataset of577 hetero-oligomeric complexes to benchmark these annotations, which reveals an accuracy &gt;94%. When homology information is not available, we compare QS across repositories (PDB, PISA, and EPPIC) to derive confidence estimates. This work provides high-quality annotations along with a large benchmark dataset of hetero-assemblies.

Fulltext

Structure

PDB-wide identification of physiological hetero-oligomeric assemblies based on conserved quaternary structure geometry

Gliomas are the most prevalent primary brain tumors with immense clinical heterogeneity, poor prognosis and survival. Gliomas arise from glial cells and are heavily infiltrated with innate immune cells. In India high-grade gliomas or Glioblastomas (GBM) account for 59.5% of CNS tumours. A key challenge for clinical management of GBM is its highly heterogeneous nature-between patients and within a single tumour-making current therapies ineffective. The nucleotide-binding domain, and leucine-rich repeat containing receptors (NLRs) and absent-in-melanoma 2 (AIM2) are innate immune receptors crucial for initiation and progression of several cancers. There is a dearth of reports investigating NLRs and AIM2 in glioma pathology.We are interested in studying the cellular and molecular contribution of NLRs and AIM2 in malignant gliomas in the Indian subcontinent. We previously reported a data-driven approach&nbsp;…

The Journal of Immunology

<a href="https://scholar.google.com/citations?view_op=view_citation&amp;hl=en&amp;user=sxkAmsoAAAAJ&amp;cstart=20&amp;pagesize=80&amp;citation_for_view=sxkAmsoAAAAJ:IWHjjKOFINEC">Understanding NLRs and AIM2 cellular and molecular signalling in glioblastoma pathophysiology</a>