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.

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Erythrocyte-based carriers can serve as theranostic platforms for delivery of imaging and therapeutic payloads. Engineering these carriers at micro- or nanoscales makes them potentially useful for broad clinical applications ranging from vascular diseases to tumor theranostics. Longevity of these carriers in circulation is important in delivering a sufficient amount of their payloads to the target. We have investigated the circulation dynamics of micro (∼4.95 μm diameter) and nano (∼91 nm diameter) erythrocyte-derived carriers in real time using near-infrared fluorescence imaging, and evaluated the effectiveness of such carrier systems in mediating photothermolysis of cutaneous vasculature in mice. Fluorescence emission half-lives of micro- and nanosized carriers in response to a single intravenous injection were ∼49 and ∼15 min, respectively. A single injection of microsized carriers resulted in a 3-fold increase in signal-to-noise ratio that remained nearly persistent over 1 h of imaging time. Our results also suggest that a second injection of the carriers 7 days later can induce a transient inflammatory response, as manifested by the apparent leakage of the carriers into the perivascular tissue. The administration of the carriers into the mice vasculature reduced the threshold laser fluence to induce photothermolysis of blood vessels from &gt;65 to 20 J/cm2. We discuss the importance of membrane physicochemical and mechanical characteristics in engineering erythrocyte-derived carriers and considerations for their clinical translation. © 2019 American Chemical Society.

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ACS Applied Materials and Interfaces

Intravital Vascular Phototheranostics and Real-Time Circulation Dynamics of Micro- And Nanosized Erythrocyte-Derived Carriers

α-Synuclein is an intrinsically disordered protein that adopts an α-helical structure upon binding to the negatively charged lipid membrane. Binding-induced conformational change of α-synuclein plays a crucial role in the regulation of synaptic plasticity. In this work, we utilized the fluorescence depolarization kinetics methodology to gain the site-specific dynamical insights into the membrane-bound α-synuclein. We took advantage of the nonoccurrence of Cys in α-synuclein and created single-Cys variants at different sites for us to be able to label it with a thiol-active fluorophore. Our fluorescence depolarization results reveal the presence of three dynamically distinct types of motions of α-synuclein on POPG (1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1′-rac-glycerol)) small unilamellar vesicles (SUVs): (i) the (local) wobbling-in-cone motion of the fluorophore on the subnanosecond timescale, (ii) the backbone segmental mobility on the nanosecond timescale, and (iii) a slow depolarization component with a characteristic long rotational correlation time (∼60 ns) that is independent of the residue position. This characteristic timescale could potentially arise due to global tumbling of the protein-membrane complex, the global reorientation of only the protein within the membrane, and/or the translation diffusion of the protein on the curved membrane surface that could result in fluorescence depolarization due to the angular displacement of the transition dipole. In order to discern the molecular origin of the characteristic long rotational correlation time, we then carried our depolarization experiments varying the curvature of the membrane and varying the binding affinity by changing the lipid headgroup. These experiments revealed that the long rotational correlation time primarily arises due to the translational diffusion of α-synuclein on the curved membrane surface with a diffusion coefficient of ∼8.7 × 10-10 m2/s. The site-specific fluorescence depolarization methodology will find broad application in quantifying diffusion of a wide range of membrane-associated proteins involved in functions and diseases. Copyright © 2020 American Chemical Society.

Journal of Physical Chemistry B

Discerning Dynamic Signatures of Membrane-Bound α-Synuclein Using Site-Specific Fluorescence Depolarization Kinetics

Fluorescent probes offer great potential to identify and treat surgical tumors by clinicians. To this end, several molecular probes were examined as in vitro and in vivo bioimaging probes. However, due to their ultra-low extinction coefficients as well as photobleaching problems, conventional molecular probes limit its practical utility. To address the above mentioned challenges, metal nanoclusters (MNCs) can serve as an excellent alternative with many unique features such as higher molar extinction coefficients/light absorbing capabilities, good photostability and appreciable fluorescence quantum yields. Herein, we reported a green synthesis of water soluble palladium nanoclusters (Pd NCs) and characterized them by using various spectroscopic and microscopic characterization techniques. These nanoclusters showed excellent photophysical properties with the characteristic emission peak centered at 500 nm under 420 nm photoexcitation wavelength. In vitro cytotoxicity studies in human cervical cancer cells (HeLa) cells reveal that Pd NCs exhibited good biocompatibility with an IC50 value of &gt;100 μg/mL and also showed excellent co-localization and distribution throughout the cytoplasm region with a significant fraction translocating into cell nucleus. We foresee that Pd NCs will carry huge potential to serve as a new generation bioimaging nanoprobe owing to its smaller size, minimal cytotoxicity, nucleus translocation capability and good cell labelling properties. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Bioengineering

Preparation, cytotoxicity, and in vitro bioimaging of water soluble and highly fluorescent palladium nanoclusters

We investigate the generation and propagation of solitary waves in the context of the Hertz chain and Toda lattice, with the aim to highlight the similarities, as well as differences between these systems. We begin by discussing the kinetic and potential energy of a solitary wave in these systems and show that under certain circumstances the kinetic and potential energy profiles in these systems (i.e., their spatial distribution) look reasonably close to each other. While this and other features, such as the connection between the amplitude and the total energy of the wave, bear similarities between the two models, there are also notable differences, such as the width of the wave. We then study the dynamical behavior of these systems in response to an initial velocity impulse. For the Toda lattice, we do so by employing the inverse scattering transform, and we obtain analytically the ratio between the energy of the resulting solitary wave and the energy of the impulse, as a function of the impulse velocity; we then compare the dynamics of the Toda system to that of the Hertz system, for which the corresponding quantities are obtained through numerical simulations. In the latter system, we obtain a universality in the fraction of the energy stored in the resulting solitary traveling wave irrespectively of the size of the impulse. This fraction turns out to only depend on the nonlinear exponent. Finally, we investigate the relation between the velocity of the resulting solitary wave and the velocity of the impulse. In particular, we provide an alternative proof for the numerical scaling rule of Hertz-type systems. © 2020, Società Italiana di Fisica and Springer-Verlag GmbH Germany, part of Springer Nature.

European Physical Journal Plus

On the generation and propagation of solitary waves in integrable and nonintegrable nonlinear lattices

We study the head-on collision of two solitary waves in a precompressed granular chain using the discrete element method. Our study takes the Toda chain solution as the initial condition for the simulations. The simulation covers the dynamical evolution of the collision process from the start of the incident wave to the end of the collision. The interaction has a central collision region of about five-grain width in which two solitary waves merge completely and share only one peak. Four stages, i.e., the pre-in-phase traveling stage, lag-phase collision state, lead-phase collision state, and post-in-phase traveling stage, are identified to describe the complex collision processes. Our results may be helpful for explaining the existence of long-lived solitary waves seen in the simulations by Takato and Sen [Europhys. Lett. 100 (2012) 24003]. © 2020 Chinese Physical Society and IOP Publishing Ltd.

Chinese Physics Letters

Head-on Collision of Solitary Waves Described by the Toda Lattice Model in Granular Chain

Malignant gliomas are the leading cause of central nervous system (CNS) tumor-related death. The failure of conventional cancer therapeutics results from the aberrant angiogenesis in gliomas. Abnormal vessel structure of gliomas, resulting in decreased delivery of chemotherapies, increased tumor hypoxia and edema leading to further complications. In this study, role of the nucleotide-binding domain, leucine rich containing (NLR) proteins in glioblastoma angiogenesis is studied. Some NLR proteins form a multi-protein complex with procaspase-1, called the “inflammasome”. Aberrant angiogenesis with torturous and leaky vessels and hypoxic core are the hallmarks of glioblastoma. Glioblastoma consists of heterogeneous population of cells such as microglial, endothelial cells, astrocytes, neurons and stromal cells. These characteristics of glioblastoma make them resistant to conventional therapy thereby&nbsp;…

IBRO Reports

<a href="https://scholar.google.com/scholar?cluster=8128031688612057346&amp;hl=en&amp;oi=scholarr">Role of the nucleotide-binding domain, leucine rich containing (NLR) proteins in glioblastoma angiogenesis</a>

Home to a culturally heterogeneous population, India is also a melting pot of genetic diversity. The population architecture characterized by multiple endogamous groups with specific marriage patterns, including the widely prevalent practice of consanguinity, not only makes the Indian population distinct from rest of the world but also provides a unique advantage and niche to understand genetic diseases. Centuries of genetic isolation of population groups have amplified the founder effects, contributing to high prevalence of recessive alleles, which translates into genetic diseases, including rare genetic diseases in India. Rare genetic diseases are becoming a public health concern in India because a large population size of close to a billion people would essentially translate to a huge disease burden for even the rarest of the rare diseases. Genomics-based approaches have been demonstrated to accelerate the diagnosis of rare genetic diseases and reduce the socio-economic burden. The Genomics for Understanding Rare Diseases: India Alliance Network (GUaRDIAN) stands for providing genomic solutions for rare diseases in India. The consortium aims to establish a unique collaborative framework in health care planning, implementation, and delivery in the specific area of rare genetic diseases. It is a nation-wide collaborative research initiative catering to rare diseases across multiple cohorts, with over 240 clinician/scientist collaborators across 70 major medical/research centers. Within the GUaRDIAN framework, clinicians refer rare disease patients, generate whole genome or exome datasets followed by computational analysis of the data for identifying the causal pathogenic variations. The outcomes of GUaRDIAN are being translated as community services through a suitable platform providing low-cost diagnostic assays in India. In addition to GUaRDIAN, several genomic investigations for diseased and healthy population are being undertaken in the country to solve the rare disease dilemma. In summary, rare diseases contribute to a significant disease burden in India. Genomics-based solutions can enable accelerated diagnosis and management of rare diseases. We discuss how a collaborative research initiative such as GUaRDIAN can provide a nation-wide framework to cater to the rare disease community of India. © 2019 The Author(s).

Human Genomics

Genomics of rare genetic diseases - Experiences from India

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.

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).