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

The endogenic microRNAs (miRNA) are evolutionary, conserved, and belong to a group of small noncoding RNAs with a stretch of 19–24 nucleotides. The miRNAs play an indispensable role in gene modulation at the posttranscriptional level, inclusive of stem-cell differentiation, embryogenesis, hematopoiesis, metabolism, immune responses, or infections. The miRNAs secreted from the cells and their presence in the biological fluids signifies the regulatory role of circulating miRNAs in the pathogenesis. The phenomenal expression levels of circulating miRNAs in serum or plasma during infection makes them the potential therapeutic biomarkers for the diagnosis of assorted human infectious diseases. In this article, we have accentuated the methods for the profiling of circulating miRNA as well as the importance of miRNA as biomarkers for the diagnosis of human infectious diseases. To date, numerous biomarkers have been identified for the diagnostic or prognostic purpose; for instance, miR-182, miR-486, and miR15a in sepsis; miR-320 and miR505 in inflammatory bowel disease; miR-155 and miR-1260 in influenza; miR-12, miRVP-3p, and miR-184 in arboviruses; and miR-29b and miR-125 in hepatitis infection. Nevertheless, the noninvasive diagnostic approach, with the aid of biomarkers, currently plays a decisive role in the untimely diagnosis of human infections. So, in the near future, the exploitation of circulating miRNAs as therapeutic biomarkers for the diagnosis of human infections will help us to cure the associated diseases promptly and effectively. © 2018 Wiley Periodicals, Inc.

World University root node

Journal of Cellular Physiology

Emerging role of circulating microRNA in the diagnosis of human infectious diseases

CAG repeats RNA causes various fatal neurodegenerative diseases exemplified by Huntington’s disease (HD) and several spinocerebellar ataxias (SCAs). Although there are differences in the pathogenic mechanisms, these diseases share the common cause, i.e., expansion of CAG repeats. The shared cause of these diseases raises the possibility for the exploiting the common target as a potential therapeutic approach. Oligonucleotide-based therapeutics are designed earlier with the help of the base pairing rule but are not very promiscuous, considering the nonspecific stimulation of the immune system and the poor cellular delivery. Therefore, small molecules-based therapeutics are preferred for targeting the repeats expansion disorders. Here, we have used the chemical similarity search approach to discern the small molecules that selectively target toxic CAG RNA. The lead compounds showed the specificity towards AA mismatch in biophysical studies including CD, ITC, and NMR spectroscopy and thus aided to forestall the polyQ mediated pathogenicity. Furthermore, the lead compounds also explicitly alleviate the polyQ mediated toxicity in HD cell models and patient-derived cells. These findings suggest that the lead compound could act as a chemical probe for AA mismatch containing RNA as well as plays a neuroprotective role in fatal neurodegenerative diseases like HD and SCAs. © 2019, The Author(s).

Fulltext

Scientific Reports

Discovery of a potent small molecule inhibiting Huntington’s disease (HD) pathogenesis via targeting CAG repeats RNA and Poly Q protein

Molecular Diagnostics in Cancer Patients

Predicting E3 Ubiquitin Ligases as Possible Promising Biomarkers for Brain Tumors

Extract of Ulmus wallichiana is being used as traditional medicine used for the treatment of fractured bones however the effect of its individual flavonols is not known. The present study was conducted to investigate the effect of its novel flavonol, (2S, 3S)-(+)-30, 40, 5, 7-tetrahydroxydihydroflavonol-6-C-b-D-glucopyranoside named as Ulmoside A (UA), on lipopolysaccharides (LPS) treated neurons. LPS treatment to neuronal cells caused significant cytotoxicity, reactive oxygen species generation, depletion in glutathione and mitochondrial impairment which were significantly inhibited with UA treatment. LPS treatment also caused significant translocation of cytochrome-c, decreased level of Bcl2, increased level of Bax and cleaved caspase-3 in neuronal cells reflecting the involvement of intrinsic apoptotic pathway in neuronal death which was attenuated with UA treatment. Since LPS is a well known pro-inflammatory agent it also offered the significant increase in proinflammatory cytokines (tumor necrosis factors-α &amp; interleukin 1-beta) however, UA treatment did not exhibit significant inhibition against LPS induced inflammatory response. LPS also caused the augmented level of inducible nitric oxide synthase (iNOS) which was also not inhibited with co treatment of UA. We have also observed the significant DNA fragmentation and augmented level of cleaved Poly (ADP-Ribose) polymerase 1 after LPS treatment which was significantly reverted with UA treatment. Findings suggested that UA acts through mitochondria and exhibited its anti-oxidative and anti-apoptotic activities in neuronal cells while no significant anti-inflammatory activity and effect on iNOS were observed. © 2019 Elsevier B.V.

Department of Electrical Engineering

NeuroToxicology

Ulmosides A: Flavonoid 6-C-glycosides from Ulmus wallichiana attenuates lipopolysacchride induced oxidative stress, apoptosis and neuronal death

Particle-based systems provide a capability for the delivery of imaging and/or therapeutic payloads. We have engineered constructs derived from erythrocytes, and doped with the FDA-approved near infrared dye, indocyanine green (ICG). We refer to these optical particles as NIR erythrocyte-mimicking transducers (NETs). A particular feature of NETs is that their diameters can be tuned from micron- to nano-scale. Herein, we investigated the effects of micron- (≈2.6 μm diameter), and nano- (≈145 nm diameter) sized NETs on their biodistribution, and evaluated their acute toxicity in healthy Swiss Webster mice. Following tail vein injection of free ICG and NETs, animals were euthanized at various time points up to 48 hours. Fluorescence analysis of blood showed that nearly 11% of the injected amount of nano-sized NETs (nNETs) remained in blood at 48 hours post-injection as compared to ≈5% for micron-sized NETs (μNETs). Similarly, at this time point, higher levels of nNETs were present in various organs including the lungs, liver, and spleen. Histological analyses of various organs, extracted at 24 hours post-injection of NETs, did not show pathological alterations. Serum biochemistry profiles, in general, did not show elevated levels of the various analyzed biomarkers associated with liver and kidney functions. Values of various hematological profiles remained within the normal ranges following the administration of μNETs and nNETs. Results of this study suggest that erythrocyte-derived particles can potentially provide a non-toxic platform for delivery of ICG. © The Royal Society of Chemistry 2018.

Biomaterials Science

Biodistribution and toxicological evaluation of micron- and nano-sized erythrocyte-derived optical particles in healthy Swiss Webster mice

The discovery of intrinsic disorderness in proteins and peptide regions has given a new and useful insight into the working of biological systems. Due to enormous plasticity and heterogeneity, intrinsically disordered proteins or regions in proteins can perform myriad of functions. The flexibility in disordered proteins allows them to undergo conformation transition to form homopolymers of proteins called amyloids. Amyloids are highly structured protein aggregates associated with many neurodegenerative diseases. However, amyloids have gained much appreciation in recent years due to their functional roles. A functional amyloid fiber called curli is assembled on the bacterial cell surface as a part of the extracellular matrix during biofilm formation. The extracellular matrix that encases cells in a biofilm protects the cells and provides resistance against many environmental stresses. Several of the Csg (curli specific genes) proteins that are required for curli amyloid assembly are predicted to be intrinsically disordered. Therefore, curli amyloid formation is highly orchestrated so that these intrinsically disordered proteins do not inappropriately aggregate at the wrong time or place. The curli proteins are compartmentalized and there are chaperone-like proteins that prevent inappropriate aggregation and allow the controlled assembly of curli amyloids. Here we review the biogenesis of curli amyloids and the role that intrinsically disordered proteins play in the process. © 2019 Elsevier B.V.

Biochimica et Biophysica Acta - Proteins and Proteomics

Bacterial functional amyloids: Order from disorder

Nucleosome assembly proteins (Naps) influence chromatin dynamics by directly binding to histones. Here we provide a comprehensive structural and biochemical analysis of a Nap protein from Caenorhabditis elegans (CeNap1). CeNap1 naturally lacks the acidic N-terminal tail and has a short C-terminal tail compared to many other Nap proteins. Comparison of CeNap1 with full length and tail-less constructs of Saccharomyces cerevisiae Nap1 uncovers the role of these tails in self-association, histone binding, and Nap competition with DNA for H2A-H2B. We find that the presence of tails influences the stoichiometry of H2A-H2B binding and is required to complete the interactions between H2A-H2B and DNA. The absolute stoichiometry of the Nap protein and H2A-H2B complex is 2:1 or 2:2, with only a very small population of higher-order oligomers occurring at 150 mM NaCl. We also show that H3-H4 binds differently than H2A-H2B and that an (H3-H4) 2 tetramer can simultaneously bind two Nap 2 protein homodimers. © 2018 American Chemical Society.

Biochemistry

Characterization of Caenorhabditis elegans Nucleosome Assembly Protein 1 Uncovers the Role of Acidic Tails in Histone Binding

We introduce PULSEDYN, a particle dynamics program written in C++, to solve the equations of motion of many-body nonlinear systems in one dimension. PULSEDYN contains a suite of commonly used potentials (Fermi–Pasta–Ulam–Tsingou, Toda, Morse and Lennard-Jones) and solvers (velocity-Verlet and Gear 5th order predictor–corrector) for particle dynamics. PULSEDYN is designed to perform scientifically accurate simulations using these calculations. For accessing the built-in features of PULSEDYN, no knowledge of programming is expected, apart from the creation of a parameter file using predefined commands for running the executable. Therefore, simulations for research projects can be performed with minimal code writing using PULSEDYN. PULSEDYN is distributed under the GNU GPL v3 license and the source code and the executable are available on Github. The writing style emphasizes organization and legibility. Therefore, we anticipate that it would serve as a good template for users who may wish to adapt the code to their specific needs. In this manuscript, we first discuss PULSEDYN and its features in detail. Then, we show results reproduced from literature using PULSEDYN for the following cases (i) Soliton propagation and collisions in the (integrable) Toda lattice (ii) Recurrence phenomena, decay of localized excitations and solitary wave collision in the Fermi–Pasta–Ulam–Tsingou lattice and (iii) Solitary wave propagation in the Morse and Lennard-Jones lattices. Finally, we present a new result on a problem of fundamental historical importance using PULSEDYN. We show by means of explicit specific heat calculations, that in the limit of strong nonlinearity, the quartic Fermi–Pasta–Ulam–Tsingou system approaches equipartition at late times. Program summary: Program Title: PULSEDYN Program Files doi: http://dx.doi.org/10.17632/fc8483t7jz.1 Licensing provisions: GNU General Public License 3 (GPL) Programming Language: C++ Supplementary Material: user manual, documentation Nature of problem: We solve a Newtonian particle dynamics problem in one dimension for a variety of commonly used nonlinear manybody systems. The goal is that the user should be able to run scientifically accurate simulations with minimal effort. Benchmarking should also be easy to perform by different users running simulations across different platforms. Solution method: The code uses a parameter file interface with a set of commands for a range of pre-built functionalities. By providing the code and the needed parameter file to the user we hope to make scientifically accurate simulations easier to perform. We provide the Gear 5th order predictor–corrector algorithm as well as the velocity-Verlet algorithm and the following potentials — the Toda potential, Morse Potential, Lennard-Jones Potential and a polynomial potential up to 4th order. To make benchmarking consistent we release the software as open source and free to distribute. © 2019 Elsevier B.V.

Computer Physics Communications

PULSEDYN—A dynamical simulation tool for studying strongly nonlinear chains

To identify the upstream signaling of aluminum-induced malate secretion through aluminum-activated malate transporter 1 (AtALMT1), a pharmacological assay using inhibitors of human signal transduction pathways was performed. Early aluminum-induced transcription of AtALMT1 and other aluminum-responsive genes was significantly suppressed by phosphatidylinositol 4-kinase (PI4K) and phospholipase C (PLC) inhibitors, indicating that the PI4K-PLC metabolic pathway activates early aluminum signaling. Inhibitors of phosphatidylinositol 3-kinase (PI3K) and PI4K reduced aluminum-activated malate transport by AtALMT1, suggesting that both the PI3K and PI4K metabolic pathways regulate this process. These results were validated using T-DNA insertion mutants of PI4K and PI3K-RNAi lines. A human protein kinase inhibitor, putatively inhibiting homologous calcineurin B-like protein-interacting protein kinase and/or Ca-dependent protein kinase in Arabidopsis, suppressed late-phase aluminum-induced expression of AtALMT1, which was concomitant with the induction of an AtALMT1 repressor, WRKY46, and suppression of an AtALMT1 activator, Calmodulin-binding transcription activator 2 (CAMTA2). In addition, a human deubiquitinase inhibitor suppressed aluminum-activated malate transport, suggesting that deubiquitinases can regulate this process. We also found a reduction of aluminum-induced citrate secretion in tobacco by applying inhibitors of PI3K and PI4K. Taken together, our results indicated that phosphatidylinositol metabolism regulates organic acid secretion in plants under aluminum stress. © The Author(s) 2019.

Journal of Experimental Botany

Involvement of phosphatidylinositol metabolism in aluminum-induced malate secretion in Arabidopsis

Interactions between cells and their environment influence key physiologic processes such as their propensity to migrate. However, directed migration controlled by extrinsically applied electrical signals is poorly understood. Using a novel microfluidic platform, we found that metastatic breast cancer cells sense and respond to the net direction of weak (∼100 µV cm−1), asymmetric, non-contact induced Electric Fields (iEFs). iEFs inhibited EGFR (Epidermal Growth Factor Receptor) activation, prevented formation of actin-rich filopodia, and hindered the motility of EGF-treated breast cancer cells. The directional effects of iEFs were nullified by inhibition of Akt phosphorylation. Moreover, iEFs in combination with Akt inhibitor reduced EGF-promoted motility below the level of untreated controls. These results represent a step towards isolating the coupling mechanism between cell motility and iEFs, provide valuable insights into how iEFs target multiple diverging cancer cell signaling mechanisms, and demonstrate that electrical signals are a fundamental regulator of cancer cell migration. © 2019, The Author(s).