Department of Bioscience & Bioengineering

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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

Speech-controlled devices have been explored for potential applications in rehabilitation technology. These systems have shown great promises in improving the independence of the differently-abled persons by providing hands-free operation of the rehabilitative aids. The present study delineates the development of a speech-activated wireless control system for controlling rehabilitative devices. A robotic arm was used as the representative rehabilitative device. This technology can be extended to operate other rehabilitative aids (e.g., wheelchairs). The performance of the device was evaluated using ten volunteers. All the volunteers were able to accurately complete the desired movements of the robotic arm with relative ease. The developed device is simple and user-friendly. Copyright © 2019 Inderscience Enterprises Ltd.

World University root node

International Journal of Biomedical Engineering and Technology

Wireless speech control system for robotic arm

Cancer subtypes identification is very important for the advancement of precision cancer disease diagnosis and therapy. It is one of the important components of the personalized medicine framework. Cervical cancer (CC) is one of the leading gynecological cancers that causes deaths in women worldwide. However, there is a lack of studies to identify histological subtypes among the patients suffering from tumor of the uterine cervix. Hence, sub-typing of cancer can help in analyzing shared molecular profiles between different histological subtypes of solid tumors of uterine cervix. With the advancement in technology, large scale multi-omics data are generated. The integration of genomics data generated from different platforms helps in capturing complementary information about the patients. Several computational approaches have been developed that integrate muti-omics data for cancer sub-typing. In this study, mRNA (messenger RNA) and miRNA (microRNA) expression data are integrated to identify the histological subtypes of CC. In this regard, a method is proposed that ranks the biomarkers (mRNA and miRNA) on the basis of their varying expression across the samples. The ranking method generates a weight for every biomarker which is further used to identify the similarity between the samples. A well-known approach named Similarity Network Fusion (SNF) is then applied, followed by Spectral clustering, to identify groups of related samples. This study focuses on the role of weighing the biomarkers prior to their integration and application of the clustering algorithm. The weighing method proposed in this study is compared with some other methods and proved to be more efficient. The proposed method helps in identifying histological subtypes of CC and can also be applied to other types of cancer data where histological subtypes play a key role in designing treatments and therapies. © 2019 IEEE.

Proceedings - 2019 IEEE 19th International Conference on Bioinformatics and Bioengineering, BIBE 2019

Importance of feature weighing in cervical cancer subtypes identification

Inherited genetic susceptibility to multiple myeloma has been investigated in a number of studies. Although 23 individual risk loci have been identified, much of the genetic heritability remains unknown. Here we carried out genome-wide interaction analyses on two European cohorts accounting for 3,999 cases and 7,266 controls and characterized genetic susceptibility to multiple myeloma with subsequent meta-analysis that discovered 16 unique interacting loci. These risk loci along with previously known variants explain 17% of the heritability in liability scale. The genes associated with the interacting loci were found to be enriched in transforming growth factor beta signaling and circadian rhythm regulation pathways suggesting immunoglobulin trait modulation, TH17 cell differentiation and bone morphogenesis as mechanistic links between the predisposition markers and intrinsic multiple myeloma biology. Further tissue/cell-type enrichment analysis associated the discovered genes with hemic-immune system tissue types and immune-related cell types indicating overall involvement in immune response. © 2019, The Author(s).

Fulltext

Communications Biology

Genome-wide interaction and pathway-based identification of key regulators in multiple myeloma

Nucleic Acids Research

PDBe-KB: a community-driven resource for structural and functional annotations

Primary neuron culture is an essential technique in the field of neuroscience. To gain deeper mechanistic insights into the brain, it is essential to have a robust in vitro model that can be exploited for various neurobiology studies. Though primary neuron cultures (i.e., long-term hippocampal cultures) have provided scientists with models, it does not yet represent the complexity of brain network completely. In the wake of these limitations, a new model has emerged using neurospheres, which bears a closer resemblance to the brain tissue. The present protocol describes the plating of high and low densities of mixed cortical and hippocampal neurons isolated from the embryo of embryonic day 14-16 Sprague Dawley rats. This allows for the generation of neurospheres and long-term primary neuron culture as two independent platforms to conduct further studies. This process is extremely simple and cost-effective, as it minimizes several steps and reagents previously deemed essential for neuron culture. This is a robust protocol with minimal requirements that can be performed with achievable results and further used for a diversity of studies related to neuroscience. © 2019 Journal of Visualized Experiments.

Journal of Visualized Experiments

Generation of neurospheres from mixed primary hippocampal and cortical neurons isolated from e14-e16 sprague dawley rat embryo

The HIV-1 envelope glycoprotein (Env) (gp120-gp41) 3 is the target for neutralizing antibodies and antibody-dependent cellular cytotoxicity (ADCC). HIV-1 Env is flexible, sampling different conformational states. Before engaging CD4, Env adopts a closed conformation (State 1) that is largely antibody resistant. CD4 binding induces an intermediate state (State 2), followed by an open conformation (State 3) that is susceptible to engagement by antibodies that recognize otherwise occluded epitopes. We investigate conformational changes in Env that induce ADCC in the presence of a small-molecule CD4-mimetic compound (CD4mc). We uncover an asymmetric Env conformation (State 2A) recognized by antibodies targeting the conserved gp120 inner domain and mediating ADCC. Sera from HIV+ individuals contain these antibodies, which can stabilize Env State 2A in combination with CD4mc. Additionally, triggering State 2A on HIV-infected primary CD4 + T cells exposes epitopes that induce ADCC. Strategies that induce this Env conformation may represent approaches to fight HIV-1 infection. HIV-1 envelope glycoproteins (Env) are very flexible and exist in at least three different conformational states. Alsahafi et al. characterize a fourth Env state that is efficiently recognized by antibodies capable of mediating potent antibody-dependent cellular toxicity. © 2019 Elsevier Inc.

Cell Host and Microbe

An Asymmetric Opening of HIV-1 Envelope Mediates Antibody-Dependent Cellular Cytotoxicity

Chemokines are chemotactic proteins involved in host defense through the migration of immune-regulatory cells to the site of infection. Interleukin-8 (CXCL8/IL8) is the most studied “ELR-CXC chemokine/neutrophil activating chemokine (NAC) that regulate neutrophil trafficking during infections and inflammation by binding to its cognate G-protein coupled receptors CXCR1/CXCR2. The “ELR” motif of NAC chemokines is essential for the CXCR1/CXCR2 receptor activation. In order to understand the evolutionary origin of “ELR” motif in the CXC chemokines, a thorough evolutionary study of CXCL8 gene from various fishes and primates was performed. Phylogenetic analysis revealed that the CXCL8 gene can be classified into four distinct lineages (CXCL8-L1a, CXCL8-L1b, CXCL8-L2, and CXCL8-L3), where CXCL8-L1a is the fastest evolving lineage and CXCL8-L3 is the slowest. Selection analysis suggested that The “ELR/DLR” motif containing branches (gadoid and coelacanth) are positively selected. The probable evolutionary trend of “ELR” motif suggested that this motif in ancestor CXCL8 is evolved from the GGR of Lamprey (Agnatha), followed by duplication giving rise to two main motifs in CXCL8 “NXH” in L3 lineage and “ELR/DLR” in L1a/L1b lineages. Although, structural analysis suggested that the overall topology of the CXCL8 proteins is similar, differences do exist at the individual structural elements among the members of different lineages. Functional distance analysis suggested that the CXCL8-L3 lineage is more distant compared to the CXCL8-L1a and L1b lineages from the inferred ancestor. Functional divergence analysis between different lineages suggested that most of the selected residues are important for receptor or glycosaminoglycan binding. Such a functional diversification can be attributed to the novel set of functions adopted by CXCL8 in various species. © 2019 Elsevier Ltd

Fish and Shellfish Immunology

Unraveling the evolutionary origin of ELR motif using fish CXC chemokine CXCL8

Lectins are proteins with a high degree of stereospecificity to recognize various sugar structures and form reversible linkages upon interaction with glyco-conjugate complexes. These are abundantly found in plants, animals and many other species and are known to agglutinate various blood groups of erythrocytes. Further, due to the unique carbohydrate recognition property, lectins have been extensively used in many biological functions that make use of protein-carbohydrate recognition like detection, isolation and characterization of glycoconjugates, histochemistry of cells and tissues, tumor cell recognition and many more. In this review, we have summarized the immunomodulatory effects of plant lectins and their effects against diseases, including antimicrobial action. We found that many plant lectins mediate its microbicidal activity by triggering host immune responses that result in the release of several cytokines followed by activation of effector mechanism. Moreover, certain lectins also enhance the phagocytic activity of macrophages during microbial infections. Lectins along with heat killed microbes can act as vaccine to provide long term protection from deadly microbes. Hence, lectin based therapy can be used as a better substitute to fight microbial diseases efficiently in future. © 2019 Elsevier Ltd

Food and Chemical Toxicology

Structure-function and application of plant lectins in disease biology and immunity

Human T-lymphotropic virus (HTLV), the first human retrovirus has been discovered which is known to cause the age-old assassinating disease HTLV-1 associated myelopathy. Cancer caused by this virus is adult T cell leukemia/lymphoma which targets 10–20 million throughout the world. The effect of this virus extends to the fact that it causes chronic disease to the spinal cord resulting in loss of sensation and further causes blood cancer. So, to overcome the complications, we designed a subunit vaccine by the assimilation of B-cell, cytotoxic T-lymphocyte, and helper T-lymphocyte epitopes. The epitopes were joined together along with adjuvant and linkers and a vaccine was fabricated which was further subjected to 3D modeling. The physiochemical properties, allergenicity, and antigenicity were evaluated. Molecular docking and dynamics were performed with the obtained 3D model against toll like receptor (TLR-3) immune receptor. Lastly, in silico cloning was performed to ensure the expression of the designed vaccine in pET28a(+) expression vector. The future prospects of the study entailed the in vitro and in vivo experimental analysis for evaluating the immune response of the designed vaccine construct. © 2018 Wiley Periodicals, Inc.

Journal of Cellular Physiology

Combinatorial screening algorithm to engineer multiepitope subunit vaccine targeting human T-lymphotropic virus-1 infection

Major neurodegenerative disorders are characterized by the formation of misfolded proteins aggregates inside or outside the neuronal cells. Previous studies suggest that aberrant proteins aggregates play a critical role in protein homeostasis imbalance and failure of protein quality control (PQC) mechanism, leading to disease conditions. However, we still do not understand the precise mechanisms of PQC failure and cellular dysfunctions associated with neurodegenerative diseases caused by the accumulation of protein aggregates. Here, we show that Myricetin, a flavonoid, can eliminate various abnormal proteins from the cellular environment via modulating endogenous levels of Hsp70 chaperone and quality control (QC)-E3 ubiquitin ligase E6-AP. We have observed that Myricetin treatment suppresses the aggregation of different aberrant proteins. Myricetin also enhances the elimination of various toxic neurodegenerative diseases associated proteins from the cells, which could be reversed by the addition of putative proteasome inhibitor (MG132). Remarkably, Myricetin can also stabilize E6-AP and reduce the misfolded proteins inclusions, which further alleviates cytotoxicity. Taken together these findings suggested that new mechanistic and therapeutic insights based on small molecules mediated regulation of disturbed protein quality control mechanism, which may result in the maintenance of the state of proteostasis. © 2019 Wiley Periodicals, Inc.