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

Aim Numerous drugs are being widely prescribed for COVID-19 treatment without any direct evidence for the drug safety/efficacy in patients across diverse ethnic populations. Materials and methods We analyzed whole genomes of 1029 Indian individuals (IndiGen) to understand the extent of drug-gene (pharmacogenetic), drug-drug and drug-drug-gene interactions associated with COVID-19 therapy in the Indian population. Results We identified 30 clinically significant pharmacogenetic variants and 73 predicted deleterious pharmacogenetic variants. COVID-19-associated pharmacogenes were substantially overlapped with those of metabolic disorder therapeutics. CYP3A4, ABCB1 and ALB are the most shared pharmacogenes. Fifteen COVID-19 therapeutics were predicted as likely drug-drug interaction candidates when used with four CYP inhibitor drugs. Conclusion Our findings provide actionable insights for future validation studies and improved clinical decisions for COVID-19 therapy in Indians. © 2021 Future Medicine Ltd.

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Pharmacogenomics

Pharmacogenomic landscape of COVID-19 therapies from Indian population genomes

Angiogenic-osteogenic cell encapsulation system is a technical need for human mesenchymal stem cell (hMSC)-based bone tissue engineering (BTE). Here, we have developed a highly efficient hMSC encapsulation system by incorporating bivalent cobalt doped nano-hydroxyapatite (HAN) and gum tragacanth (GT) as angiogenic-osteogenic components into the calcium alginate (CA) beads. Physico-chemical characterizations revealed that the swelling and degradation of HAN incorporated CA-GT beads (GT-HAN) were 1.34 folds and 2 folds higher than calcium alginate (CA) beads. Furthermore, the diffusion coefficient of solute molecule was found 2.5-fold higher in GT-HAN with respect to CA bead. It is observed that GT-HAN supports the long-term viability of encapsulated hMSC and causes 50% less production of reactive oxygen species (ROS) in comparison to CA beads. The expression of osteogenic differentiation markers was found 1.5–2.5 folds higher in the case of GT-HAN in comparison to CA. A similar trend was observed for hypoxia inducible factor 1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF). The soluble secretome from hMSC encapsulated in the GT-HAN induced proliferation of endothelial cells and supported tube formation (2.5-fold higher than CA beads). These results corroborated that GT-HAN could be used as an angiogenic-osteogenic cell encapsulation matrix for hMSC encapsulation and BTE application. © 2021 Elsevier B.V.

International Journal of Biological Macromolecules

Cobalt doped nano-hydroxyapatite incorporated gum tragacanth-alginate beads as angiogenic-osteogenic cell encapsulation system for mesenchymal stem cell based bone tissue engineering

In this study, a series of novel composite films comprised of poly (vinyl alcohol) (PVA), tamarind gum (TG), and bentonite clay particles were prepared using the solvent casting method. The prepared composite films appeared colorless and transparent. Ultraviolet-visible (UV–vis) spectroscopy revealed that the prepared films showed higher absorption in the UV region as compared to the visible region. Bright-field microscopy analysis showed that the matrix of the films contained globular architectures. The analysis of the surface topological features of the prepared films suggested the agglomeration of clay particles in the PVA/TG matrix when the bentonite content was higher. Bentonite-containing films had higher %swelling as compared to the control (PVA/TG) film. FTIR spectroscopy indicated that the incorporation of the bentonite clay enhanced the hydrogen bonding among the components of the films. X-ray diffraction analysis of the films suggested the intercalation of polymer chains within the bentonite clay layers when the bentonite content was lower. However, the filler particles assumed agglomerated forms as the loading concentration of bentonite was increased, which was in agreement with SEM analysis. On the other hand, mechanical studies suggested that above a critical amount (i.e., 20 mg), bentonite weakened the network structure of the films. The resistive component of the films showed a gradual increment with a corresponding rise in the bentonite content. The in vitro release study confirmed that the films loaded with ciprofloxacin HCl supported the sustained diffusion of the drug molecules and hence, can be utilized for controlled drug delivery applications. Moreover, the drug-loaded films showed an effective antimicrobial effect against Gram-positive and Gram-negative microbes as compared to the control films. In gist, the above analyses suggested that the prepared PVA/TG/bentonite films have promising potential to be utilized as drug delivery systems. © 2021 Elsevier B.V.

Colloids and Surfaces A: Physicochemical and Engineering Aspects

Synthesis of novel poly (vinyl alcohol)/tamarind gum/bentonite-based composite films for drug delivery applications

Information processing in the brain is mediated through a complex functional network architecture whose comprising nodes integrate and segregate themselves on different timescales. To gain an understanding of the network function it is imperative to identify and understand the network structure with respect to the underlying anatomical connectivity and the topographic organization. Here we show that the previously described resting-state network for the somatosensory area 3b comprises of distinct networks that are characteristic for different topographic representations. Seed-based resting-state functional connectivity analysis in macaque monkeys and humans using BOLD-fMRI signals from the face, the hand and rest of the medial somatosensory representations of area 3b revealed different correlation patterns. Both monkeys and humans have many similarities in the connectivity networks, although the networks are more complex in humans with many more nodes. In both the species face area network has the highest ipsilateral and contralateral connectivity, which included areas 3b and 4, and ventral premotor area. The area 3b hand network included ipsilateral hand representation in area 4. The emergent functional network structures largely reflect the known anatomical connectivity. Our results show that different body part representations in area 3b have independent functional networks perhaps reflecting differences in the behavioral use of different body parts. The results also show that large cortical areas if considered together, do not give a complete and accurate picture of the network architecture. © 2020 The Authors

NeuroImage

Resting-State functional networks of different topographic representations in the somatosensory cortex of macaque monkeys and humans

Reflecting its pleiotropic functions, Polo-like kinase 1 (PLK1) localizes to various sub-cellular structures during mitosis. At kinetochores, PLK1 contributes to microtubule attachments and mitotic checkpoint signaling. Previous studies identified a wealth of potential PLK1 receptors at kinetochores, as well as requirements for various mitotic kinases, including BUB1, Aurora B, and PLK1 itself. Here, we combine ectopic localization, in vitro reconstitution, and kinetochore localization studies to demonstrate that most and likely all of the PLK1 is recruited through BUB1 in the outer kinetochore and centromeric protein U (CENP-U) in the inner kinetochore. BUB1 and CENP-U share a constellation of sequence motifs consisting of a putative PP2A-docking motif and two neighboring PLK1-docking sites, which, contingent on priming phosphorylation by cyclin-dependent kinase 1 and PLK1 itself, bind PLK1 and promote its dimerization. Our results rationalize previous observations and describe a unifying mechanism for recruitment of PLK1 to human kinetochores. © 2020 The Author(s) Polo-like kinase 1 (PLK1) targets kinetochores to regulate microtubule attachment and mitotic checkpoint signaling. Singh et al. show how CDK1 and PLK1 promote kinetochore recruitment and dimerization of PLK1 onto BUB1 and CENP-U, probably the only PLK1 receptors in the core kinetochore. A conserved constellation of docking sites in BUB1 and CENP-U, including one for PP2A phosphatase, suggests a common regulatory switch. © 2020 The Author(s)

Molecular Cell

BUB1 and CENP-U, Primed by CDK1, Are the Main PLK1 Kinetochore Receptors in Mitosis

Objective Ascaris lumbricoides infects 80 million people per year, causing malnutrition, stunted growth of children etc., but there is no vaccine available against it. We aimed to design a multimeric-subunit vaccine using comprehensive immunoinformatic approach. Research design and Methods The T and B cell epitopes were shortlisted on antigenicity, allergenicity, and toxicity from proteome data and joined with appropriate linkers. The physical characteristics of vaccine candidate was calculated and docking/molecular dynamic simulation performed to validate its robustness. The multimeric protein was codon optimized and in-silico cloned in pET28b. Results From the 23,604 proteins of Ascaris, we filtered based on epitope prediction, localization, antigenicity, and allergenicity. Prepared a vaccine of 534 amino acid long, 56.31 kD weight and pI 4.52. Physiochemical features showed it is soluble, highly antigenic and non-allergenic. Its tertiary structure was forecasted, certified, and refined. The immunoinformatic simulation studies showed it to be potent T and B cell stimulator. Conclusions We identified highly antigenic peptides of Ascaris from its proteome with good potential to induce innate as well as humoral immune response. These peptides were used to design a chimeric vaccine against Ascariasis infection, which can be used for prophylactic purpose but needs experimental and clinical validation.

EXPERT REVIEW OF VACCINES

Immunoinformatics driven construction of multi-epitope vaccine candidate against Ascaris lumbricoides using its entire immunogenic epitopes

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field. © 2020 Informa UK Limited, trading as Taylor & Francis Group.

Autophagy

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1

Evidence accumulated from past findings indicates that defective proteostasis may contribute to risk factors for cancer generation. Irregular assembly of abnormal proteins catalyzes the disturbance of cellular proteostasis and induces the ability of abnormal cellular proliferation. The autophagy mechanism plays a key role in the regular clearance of abnormal/poor lipids, proteins, and various cellular organelles. The results of functional and effective autophagy deliver normal cellular homeostasis, which establishes supportive metabolism and avoids unexpected tumorigenesis events. Still, the precise molecular mechanism of autophagy in tumor suppression has not been clear. How autophagy triggers selective or nonselective bulk degradation to dissipate tumor promotion under stress conditions is not clear. Under proteotoxic insults to knockdown the drive of tumorigenesis, it is critical for us to figure out the detailed molecular functions of autophagy in human cancers. The current article summarizes autophagy-based theragnostic strategies targeting various phases of tumorigenesis and suggests the preventive roles of autophagy against tumor progression. A better understanding of various molecular partners of autophagic flux will improve and innovate therapeutic approaches based on autophagic-susceptible effects against cellular oncogenic transformation.

JOURNAL OF CELLULAR PHYSIOLOGY

Autophagy based cellular physiological strategies target oncogenic progression

Introduction Taenia solium infection is among the 17 most neglected tropical diseases identified by World Health Organization and to be eradicated by 2030. This parasite infects the central nervous system (Neurocysticercosis {[}NCC]) and intestine {[}Taeniasis]). NCC is the most frequent cause of acquired epilepsy in endemic regions and Taeniasis is responsible for the widespread malnutrition and abdominal discomfort among children. Epilepsy caused by T. solium is preventable and the total elimination of NCC can be achieved by good hygiene, mass therapy, and most importantly vaccination of pigs or humans. Vaccine for pig is available but not widely in use and for humans it's still elusive. Area covered Several vaccine candidates for porcine cysticercosis have been tried like TSOL18, SP3Vac, KETc7, TSOL45, etc. with good success in the limited field trial. This review highlights some seminal contributions for the anti-cestode vaccine, the associated challenges, current status, suggestive future directions, and the need of vaccine for human use. Expert opinion Though several vaccines are available, none is being widely used due to lack of awareness, economic constraints, accessibility, etc. Hence, there is a need for a newer, economic, and reliable vaccine for humans or pigs use to reduce the disease burden.

Vaccine for a neglected tropical disease Taenia solium cysticercosis: fight for eradication against all odds

Ovarian cancer is the most lethal malignancy affecting the female reproductive system. Identification and removal of all ovarian intraperitoneal tumor deposits during the intraoperative surgery is important towards preventing cancer recurrence and ultimately improving patient survival. Herein, we investigate the effectiveness of virus mimicking nanoparticles, derived from genome-depleted plant-infecting brome mosaic virus, and doped with near infrared (NIR) brominated cyanine dye BrCy106-NHS, for targeted NIR fluorescence imaging of intraperitoneal ovarian tumors. We refer to these nanoparticles as optical viral ghosts (OVGs). We functionalized the OVGs with antibodies against HER2 receptor, a biomarker over-expressed in ovarian cancers. We injected functionalized OVGs, non-functionalized OVGs, and non-encapsulated BrCy106-NHS intravenously in mice implanted with ovarian intraperitoneal tumors. Tumors were extracted at 2, 6, and 24 h post-injection, and quantitatively analyzed using NIR fluorescence imaging. Fluorescence emission from tumors associated with the injection of the functionalized OVGs continued to increase between 2 and 24 h post-injection. At 24 h timepoint, the average spectrally-integrated fluorescence emission from homogenized tumors containing functionalized-OVGs was about 3.5 and 19.5 times higher than those containing non-functionalized OVGs or non-encapsulated BrCy106-NHS, respectively. Similarly, by using the functionalized-OVGs, the imaging signal-to-noise ratio at 24 h timepoint was enhanced by approximately threefold and sevenfold as compared to non-functionalized OVGs and the non-encapsulated dye, respectively. These functionalized virus-mimicking NIR nano-constructs could potentially be used for intraoperative visualization of ovarian tumors implants. © 2020, Biomedical Engineering Society.