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

We report the assembly behavior of an antimitotic cell penetrating peptide (CPP) bound with membrane and in solution using experimental and computational techniques. Our study reveals that the antimitotic peptide spontaneously self-assembles and forms a β-sheet-like structure, which is important for cellular entry. Further, we found that this peptide strongly interacts with both liposome membrane and MCF7 membrane. Interestingly, we observed that, during interaction with both lipid membrane and cell membrane, the peptide fluctuates (oscillates) in a similar pattern. The fluctuations in the fluorescence intensity of fluorescein-labeled peptide in the membrane of liposome and cell are attributed to the fluctuation of fluorescein between non-fluorescent neutral form and highly fluorescent dianion form (i.e., prototropic processes). The rate of fluctuation or oscillation is significantly faster at the cell membrane (0.75 s) than that (1.4 s) at the liposome membrane. © 2019 American Chemical Society.

World University root node

Fulltext

ACS Omega

Self-Assembly of Antimitotic Peptide at Membranes: Computational and Experimental Investigation

In the past decade of research, drugs targeting amyloid beta (Aβ) have failed in clinical amelioration of Alzheimer's disease (AD). This has led to researchers searching for more attractive targets. Here, we discuss one such approach of developing future neurotherapeutics by targeting microtubules. Microtubules are the key structural and functional elements of neurons and have been found to be closely associated with neurodegenerative disorders like AD due to their association with tau. Tau is a microtubule associated protein whose abnormal phosphorylation leads to microtubule destabilization giving rise to variable tauopathies associated with different neurodegenerative disorders. Due to this association of microtubules with tau and their importance in neurons, microtubules can be considered as one of the important supplementary targets for designing future neurotherapeutics. © 2019 American Chemical Society.

ACS Chemical Neuroscience

Why Microtubules Should Be Considered as One of the Supplementary Targets for Designing Neurotherapeutics

Alzheimer's disease (AD) is a constantly recurring neurodegenerative disease that deteriorates over a period of time. In this pathology, connections between neurons become extremely damaged due to the deposition of senile plaques in the membrane region, which results in abnormal signal transduction processes. Also, the intracellular microtubule networks are disrupted in the hyperphosphorylated tau cascade of AD. Therefore, design and development of potent neuroprotective molecules that can instantaneously target multiple facets of AD pathogenesis are greatly needed to tackle this unmet medical need. Here, we have implemented a pharmacophore based in silico analysis of various neuroprotective peptides known for neurotherapeutic application in AD. Fascinatingly, we have identified an active core of these peptides and designed a library of hexapeptides. We observed that peptide "LETVNQ" (LE6) has shown significant protection ability against degeneration of neurons. Experimental evidence suggests that this peptide immensely reduced the aggregation rate of amyloid-β (Aβ) and helped in microtubule polymerization. Intriguingly, this newly designed peptide does not have any cytotoxicity toward differentiated PC12 neurons; rather it helps in neurite outgrowth. Further, LE6 helps to maintain the complex microtubule network in cells by promoting the polymerization rate of intracellular microtubules and mediates excellent protection of neurons even after removal of nerve growth factor (NGF). Finally, we observed that this LE6 peptide has substantial stability under physiological conditions and helps to retain healthy morphology of primary rat cortical neurons. This excellent piece of work identifies a potent hexapeptide, which has exceptional ability to protect neurons as well as microtubule from degeneration and may become potent therapeutics against AD pathogenesis in the future. © 2019 American Chemical Society.

In Silico Approach for Designing Potent Neuroprotective Hexapeptide

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.

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).

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.