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

Breast cancer is the second leading cause of cancer deaths among women. Cannabinoid receptor 2 (CNR2 or CB2) is an integral part of the endocannabinoid system. Although CNR2 is highly expressed in the breast cancer tissues as well as breast cancer cell lines, its functional role in breast tumorigenesis is not well understood. We observed that estrogen receptor-a negative (ERa-) breast cancer cells highly express epidermal growth factor receptor (EGFR) as well as insulin-like growth factor-I receptor (IGF-IR). We also observed IGF-IR upregulation in ERa+ breast cancer cells. In addition, we found that higher CNR2 expression correlates with better recurrence free survival in ERa- and ERa+ breast cancer patients. Therefore, we analyzed the role of CNR2 specific agonist (JWH-015) on EGF and/ or IGF-I-induced tumorigenic events in ERa- and ERa+ breast cancers. Our studies showed that CNR2 activation inhibited EGF and IGF-I-induced migration and invasion of ERa+ and ERa- breast cancer cells. At the molecular level, JWH-015 inhibited EGFR and IGF-IR activation and their downstream targets STAT3, AKT, ERK, NFkB and matrix metalloproteinases (MMPs). In vivo studies showed that JWH-015 significantly reduced breast cancer growth in ERa+ and ERa- breast cancer mouse models. Furthermore, we found that the tumors derived from JWH-015-treated mice showed reduced activation of EGFR and IGF-IR and their downstream targets. In conclusion, we show that CNR2 activation suppresses breast cancer through novel mechanisms by inhibiting EGF/EGFR and IGF-I/IGF-IR signaling axes.

World University root node

Oncotarget

Novel role of cannabinoid receptor 2 in inhibiting EGF/EGFR and IGF-I/IGF-IR pathways in breast cancer

This study discusses about the effect of polysaccharides (agar, gum tragacanth, and guar gum) on the properties of the core (organogel)–shell [poly(vinyl alcohol)] microparticles. The size, swelling, and mucoadhesive properties of the poly(vinyl alcohol) microparticles were altered in the presence of the polysaccharides. Thermal analysis confirmed the presence of organogels within the microparticles. Fourier transform infrared spectroscopy confirmed the presence of the polysaccharides within the microparticles. The microparticles were biocompatible in nature. Drug release indicated that an alteration in the shell composition can be used for altering drug release. Ciprofloxacin-loaded microparticles showed sufficient antimicrobial efficiency. © 2016, Copyright © Taylor & Francis Group, LLC.

Polymer - Plastics Technology and Engineering

Effect of Polysaccharides on the Properties of the Mucoadhesive Poly(Vinyl Alcohol) Multicore–Shell Microparticles

Modulation of crystallization of stearic acid and its derivatives is important for tuning the properties of stearate oleogels. The present study delineates the crystallization of stearic acid in stearate oleogels in the presence of Span 60. Microarchitecture analysis revealed that stearic acid crystals in the oleogels changed its shape from plate-like structure to a branched architecture in the presence of Span 60. Consequently, a significant variation in the mobility of the solute molecules inside the oleogel (Fluorescence recovery after photobleaching studies, FRAP analysis) was observed. Thermal analysis (gelation kinetics and DSC) revealed shortening of nucleation induction time and secondary crystallization with an increase in the Span 60 concentration. Furthermore, isosolid diagram suggested better physical stability of the formulations at higher proportions of Span 60. XRD analysis indicated that there was a decrease in the crystal size and the crystallinity of the stearic acid crystals with an increase in Span 60 concentration in the Span 60 containing oleogels. However, crystal growth orientation was unidirectional and found unaltered with Span 60 concentration (Avarmi analysis using DSC data). The mechanical study indicated a composition-dependent variation in the viscoelastic properties (instantaneous [τ1], intermediate [τ2], and delayed [τ3] relaxation times) of the formulations. In conclusion, Span 60 can be used to alter the kinetics of the crystallization, crystal habit and crystal structure of stearic acid. This study provides a number of clues that could be used further for developing oleogel based formulation. Practical Application: Stearic acid can be used for the solidification of vegetable oils. This will allow easy handling, storage and transportation of the oils. The physical and the thermal properties of the oleogels can be altered by tailoring the microstructure of the oleogels using Span 60 (nonionic surfactant). The oleogels can be used for the controlled delivery of nutraceuticals and drugs. © 2016 Institute of Food Technologists®.

Journal of Food Science

Effect of Span 60 on the Microstructure, Crystallization Kinetics, and Mechanical Properties of Stearic Acid Oleogels: An In-Depth Analysis

The present study delineates the preparation, characterization and application of gelatin-carboxymethyl chitosan scaffolds for dermal tissue engineering. The effect of carboxymethyl chitosan and gelatin ratio was evaluated for variations in their physico-chemical-biological characteristics and drug release kinetics. The scaffolds were prepared by freeze drying method and characterized by SEM and FTIR. The study revealed that the scaffolds were highly porous with pore size ranging between 90 and 170 μm, had high water uptake (400–1100%) and water retention capacity (>300%). The collagenase mediated degradation of the scaffolds was dependent on the amount of gelatin present in the formulation. A slight yet significant variation in their biological characteristics was also observed. All the formulations supported adhesion, spreading, growth and proliferation of 3T3 mouse fibroblasts. The cells seeded on the scaffolds also demonstrated expression of collagen type I, HIF1α and VEGF, providing a clue regarding their growth and proliferation along with potential to support angiogenesis during wound healing. In addition, the scaffolds showed sustained ampicillin and bovine serum albumin release, confirming their suitability as a therapeutic delivery vehicle during wound healing. All together, the results suggest that gelatin-carboxymethyl chitosan based scaffolds could be a suitable matrix for dermal tissue engineering applications. © 2016 Elsevier B.V.

International Journal of Biological Macromolecules

Gelatin/Carboxymethyl chitosan based scaffolds for dermal tissue engineering applications

Success of bone tissue engineering (BTE) relies on the osteogenic microarchitecture of the biopolymeric scaffold and appropriate spatiotemporal distribution of therapeutic molecules (growth factors and drugs) inside it. However, the existing technologies have failed to address both the issues together. Keeping this perspective in mind, we have developed a novel three-dimensional (3D) implant prototype by stacking hexagonal close packed (HCP) layers of calcium alginate beads. The HCP arrangement of the beads lead to a patterned array of interconnected tetrahedral and octahedral pores of average diameter of 142.9 and 262.9 μm, respectively, inside the implant. The swelling pattern of the implants changed from isotropic to anisotropic in the z-direction in the absence of bivalent calcium ions (Ca2+) in the swelling buffer. Incubation of the implant in simulated body fluid (SBF) resulted in a 2.7-fold increase in the compressive modulus. The variation in the relaxation times as derived from the Weichert viscoelasticity model predicted a gradual increase in the interactions among the alginate molecules in the matrix. We demonstrated the tunability of the spatiotemporal drug release from the implant in a tissue mimicking porous semisolid matrix as well as in conventional drug release set up by changing the spatial coordinates of the "drug loaded depot layer" inside the implant. The therapeutic potential of the implant was confirmed against Escherichia coli using metronidazole as the model drug. Detailed analysis of cell viability, cell cycle progression, and cytoskeletal reorganization using osteoblast cells (MG-63) proved the osteoconductive nature of the implant. Expression of differentiation markers such as alkaline phosphatase, runx2, and collagen type 1 in human mesenchymal stem cell in vitro confirmed the osteogenic nature of the implant. When tested in vivo, VEGF loaded implant was found capable of inducing angiogenesis in a mice model. In conclusion, the bead based implant may find its utility in non-load-bearing BTE. © 2016 American Chemical Society.

ACS Applied Materials and Interfaces

Alginate Bead Based Hexagonal Close Packed 3D Implant for Bone Tissue Engineering

In the present times need is being felt for a change in paradigm from the current practice of modern medicine. This is not only to meet the challenges in diagnosis and treatment of chronic and complex diseases but also to address the variability in therapeutic outcome as well as evolve preventive measures in health and disease. The advent of genomics has provided a tremendous impetus to this area. However, there are a number of gaps before this is realized. Ayurveda, the ancient Indian system of predictive and personalized medicine still holds contemporary in the current era of P4 (predictive, preventive, personalized, and participatory) medicine and also has a promotive component. Ayurveda has documented methods for maintenance of health and personalized management of diseases. It is also widely practiced in most Indian communities despite sociocultural variations and many aspects for preventive health are also integrated into Indian traditional living. Despite this a large number of challenges exist in getting this system to mainstream and for its global acceptability. This review highlights some of these aspects and also proposes Ayurgenomics as a novel approach for integration of Ayurveda into current medical practice. © 2016 Elsevier Inc.

Genomics and Society: Ethical, Legal, Cultural and Socioeconomic Implications

Genomics and Traditional Indian Ayurvedic Medicine

Primate-specific Alus harbor different regulatory features, including miRNA targets. In this study, we provide evidence for miRNA-mediated modulation of transcript isoform levels during heat-shock response through exaptation of Alu-miRNA sites in mature mRNA. We performed genome-wide expression profiling coupled with functional validation of miRNA target sites within exonized Alus, and analyzed conservation of these targets across primates. We observed that two miRNAs (miR-15a-3p and miR-302d-3p) elevated in stress response, target RAD1, GTSE1, NR2C1, FKBP9 and UBE2I exclusively within Alu. These genes map onto the p53 regulatory network. Ectopic overexpression of miR-15a-3p downregulates GTSE1 and RAD1 at the protein level and enhances cell survival. This Alu-mediated fine-tuning seems to be unique to humans as evident from the absence of orthologous sites in other primate lineages. We further analyzed signatures of selection on Alu-miRNA targets in the genome, using 1000 Genomes Phase-I data. We found that 198 out of 3177 Alu-exonized genes exhibit signatures of selection within Alu-miRNA sites, with 60 of them containing SNPs supported by multiple evidences (global-FST &gt; 0.3, pair-wise-FST &gt; 0.5, Fay-Wu's H &lt;-20, iHS &gt; 2.0, high δ"DAF) and implicated in p53 network. We propose that by affecting multiple genes, Alu-miRNA interactions have the potential to facilitate population-level adaptations in response to environmental challenges. © 2016 The Author(s).

Fulltext

Scientific Reports

Alu-miRNA interactions modulate transcript isoform diversity in stress response and reveal signatures of positive selection

In this paper, we combine kinetic modelling and patient gene expression data analysis to elucidate biological mechanisms by which melanoma becomes resistant to the immune system and to immunotherapy. To this end, we systematically perturbed the parameters in a kinetic model and performed a mathematical analysis of their impact, thereby obtaining signatures associated with the emergence of phenotypes of melanoma immune sensitivity and resistance. Our phenotypic signatures were compared with published clinical data on pretreatment tumor gene expression in patients subjected to immunotherapy against metastatic melanoma. To this end, the differentially expressed genes were annotated with standard gene ontology terms and aggregated into metagenes. Our method sheds light on putative mechanisms by which melanoma may develop immunoresistance. Precisely, our results and the clinical data point to the existence of a signature of intermediate expression levels for genes related to antigen presentation that constitutes an intriguing resistance mechanism, whereby micrometastases are able to minimize the combined anti-tumor activity of complementary responses mediated by cytotoxic T cells and natural killer cells, respectively. Finally, we computationally explored the efficacy of cytokines used as low-dose co-adjuvants for the therapeutic anticancer vaccine to overcome tumor immunoresistance.

Model-based genotype-phenotype mapping used to investigate gene signatures of immune sensitivity and resistance in melanoma micrometastasis

A microtubule targeted peptide-based delivery vehicle has been designed using two oppositely charged peptides, which targets tubulin/microtubules, delivers both hydrophilic and hydrophobic drugs into their target site through lysosome at acidic pH. Drug loaded vesicles show a significant anticancer effect compared to control drugs in a 2D monolayer and a 3D spheroid cell. © The Royal Society of Chemistry 2016.

Chemical Communications

Design of a novel microtubule targeted peptide vesicle for delivering different anticancer drugs

A novel bi-functional liposome is designed using two novel lipo peptides, which delivers docetaxel specifically to melanoma cell targeting integrin (α4β1) and ephrin (EphA2) receptors and enhances efficacy of docetaxel in melanoma cells. © The Royal Society of Chemistry.