Department of Biotechnology

Indian Institute of Technology Hyderabad (IITH) is a premier institute of science and technology established in 2008. IITH has been consistently ranked in the&nbsp;<a href="https://iith.ac.in/reports/" rel="noopener noreferrer">top 10 institutes</a>&nbsp;in India for Engineering&nbsp;<a href="https://www.nirfindia.org/2021/EngineeringRanking.html" rel="noopener noreferrer" target="_blank">according to NIRF</a>&nbsp;making it one of the most coveted schools for science and technology in the country.

IITH offers&nbsp;<a href="https://iith.ac.in/academics/under-graduate/">undergraduate programs</a>&nbsp;in all the classical engineering disciplines, applied sciences, design, as well as several modern interdisciplinary areas. Students are given a flexibility to explore a broad set of areas, and potentially pursue a minor or double major in a discipline that is not their own. Students who wish to seek a deeper understanding of their own discipline are strongly encouraged to get involved in cutting-edge research with the help of a faculty to mentor them, and earn an Honors in their own field.

The very foundation of IIT Hyderabad is based on&nbsp;<a href="https://iith.ac.in/research/">research and innovation</a>. The vibrant research culture is evident from the number of patents and publications that IITH produces consistently every year. IITH offers&nbsp;<a href="https://iith.ac.in/academics/programmes-offered/">graduate programs</a>&nbsp;at both a masters, and a doctoral level, in several diverse areas. There are separate programs for technology, design, science, and liberal arts. The&nbsp;<a href="https://iith.ac.in/academics/post-graduate/">MTech program</a>&nbsp;is offered in various modes and durations to cater to the ever-growing need of postgraduate level professionals in the country.

IITH encourages and supports&nbsp;<a href="https://iic-iith.netlify.app/index.html" rel="noopener noreferrer" target="_blank">innovation and entrepreneurship</a>&nbsp;at every stage. The minor program in entrepreneurship is open to all students of IITH, and many of the courses are offered by industrialists who are entrepreneurs themselves. There are various&nbsp;<a href="https://iith.ac.in/research/centres-incubators/">innovation centers and incubators</a>&nbsp;that promote entrepreneurship and help mentor young innovators. IITH has been very successful in building tie-ups with leading academic institutions around the globe.

IITH enjoys a very special relationship with Japanese universities and industries that goes beyond academic and research collaborations. In fact, some of the iconic buildings in IITH campus will carry the signature of Japanese architecture.

IITH creates a unique holistic ecosystem for education that offers interactive learning, a very flexible academic structure, cutting-edge research, strong industry collaboration, and entrepreneurship. This is an environment which enables students and faculty to translate their dreams into realities.

IIT Hyderabad

Cellular processes, such as DNA replication, recombination and transcription, require DNA strands separation and single-stranded DNA is formation. The single-stranded DNA is promptly wrapped by human single-stranded DNA binding proteins, replication protein A (RPA) complex. RPA binding not only prevent nuclease degradation and annealing, but it also coordinates cell-cycle checkpoint activation and DNA repair. However, RPA binding offers little protection against the chemical modification of DNA bases. This review focuses on the type of DNA base damage that occurs in single-stranded DNA and how the damage is rectified in human cells. The discovery of DNA repair proteins, such as ALKBH3, AGT, UNG2, NEIL3, being able to repair the damaged base in the single-stranded DNA, renewed the interest to study single-stranded DNA repair. These mechanistically different proteins work independently from each other with the overarching goal of increasing fidelity of recombination and promoting error-free replication. © 2020 Elsevier B.V.

DNA Repair

Single-stranded DNA damage: Protecting the single-stranded DNA from chemical attack

Nanopore sequencing of nucleic acids has an illustrious history of innovations that eventually made commercial nanopore sequencing possible. Nevertheless, the present nanopore sequencing technology leaves much room for improvement, especially with respect to accuracy of raw reads and detection of nucleotide modifications. Double-nanopore sequencing-an approach where a DNA molecule is pulled back and forth by a tug-of-war of two nanopores-could potentially improve single-molecule read accuracy and modification detection by offering multiple reads of the same DNA fragment. One principle difficulty in realizing such a technology is threading single-stranded DNA through both nanopores. Here, we describe and demonstrate through simulations a nanofluidic system for loading and threading DNA strands through a double-nanopore setup with nearly 100% fidelity. The high-efficiency loading is realized by using hourglass-shaped side channels that not only deliver the molecules to the nanopore but also retain molecules that missed the nanopore at the first passage to attempt the nanopore capture again. The second nanopore capture is facilitated by an orthogonal microfluidic flow that unravels the molecule captured by the first nanopore and delivers it to the capture volume of the second nanopore. We demonstrate the potential utility of our double-nanopore system for DNA sequencing by simulating repeat back-and-forth motion-flossing-of a DNA strand through the double-nanopore system. We show that repeat exposure of the same DNA fragments to the nanopore sensing volume considerably increases accuracy of the nucleotide sequence determination and that correlated displacement of ssDNA through the two nanopores may facilitate recognition of homopolymer fragments. © 2020 American Chemical Society.

World University root node

ACS Nano

High-fidelity capture, threading, and infinite-depth sequencing of single DNA molecules with a double-nanopore system

Aims: Despite the advanced cancer treatments, there is increased resistance to chemotherapy and subsequent mortality. In lack of reliable data in monolayer cultures and animal models, researchers are shifting to 3D cancer spheroids, which represents the in vivo robust tumour morphology. Calcium is essential in cell signalling and proliferation. It is found that T-type calcium channels (TTCCs) are overexpressed in various cancer cells, supporting their increased proliferation. Many of the TTCCs blockers available could target other channels besides TTCCs, which can cause adverse effects. Therefore, we hypothesise that TTA-A2, a highly selective blocker towards TTCCs, can inhibit the growth of cancer spheroids, and provide an anti-cancer and an adjuvant role in cancer therapy. Methods: We studied TTA-A2 and paclitaxel (PTX-control drug) in lung adenocarcinoma cell line- A549, cancer cells and human embryonic kidney cell line- HEK 293, control cell, in their monolayer and spheroids forms for viability, proliferation, morphology change, migration, and invasion-after 48–96 h of treatment. Key findings: Though the results varied between the monolayer and spheroids studies, we found both anti-cancer as well as adjuvant effect of TTA-A2 in both the studies. TTA-A2 was able to inhibit the growth, viability, and metastasis of the cancer cells and spheroids. Differences in the results of two modes might explain that why drugs tested successfully in monolayer culture fail in clinical trials. Significance: This study establishes the role of TTA-A2, a potent TTCC blocker as an anti-cancer and adjuvant drug in reducing the viability and metastasis of the cancer cells. © 2020 Elsevier Inc.

Department of Biomedical Engineering

Life Sciences

T-type calcium channel antagonist, TTA-A2 exhibits anti-cancer properties in 3D spheroids of A549, a lung adenocarcinoma cell line

Coronovirus disease 2019 (COVID-19) infection, which originated from Wuhan, China, has seized the whole world in its grasp and created a huge pandemic situation before humanity. Since December 2019, genomes of numerous isolates have been sequenced and analyzed for testing confirmation, epidemiology, and evolutionary studies. In the first half of this article, we provide a detailed review of the history and origin of COVID-19, followed by the taxonomy, nomenclature and genome organization of its causative agent Severe Acute Respiratory Syndrome-related Coronavirus-2 (SARS-CoV-2). In the latter half, we analyze subgenus Sarbecovirus (167 SARS-CoV-2, 312 SARS-CoV, and 5 Pangolin CoV) genomes to understand their diversity, origin, and evolution, along with pan-genome analysis of genus Betacoronavirus members. Whole-genome sequence-based phylogeny of subgenus Sarbecovirus genomes reasserted the fact that SARS-CoV-2 strains evolved from their common ancestors putatively residing in bat or pangolin hosts. We predicted a few country-specific patterns of relatedness and identified mutational hotspots with high, medium and low probability based on genome alignment of 167 SARS-CoV-2 strains. A total of 100-nucleotide segment-based homology studies revealed that the majority of the SARS-CoV-2 genome segments are close to Bat CoV, followed by some to Pangolin CoV, and some are unique ones. Open pan-genome of genus Betacoronavirus members indicates the diversity contributed by the novel viruses emerging in this group. Overall, the exploration of the diversity of these isolates, mutational hotspots and pan-genome will shed light on the evolution and pathogenicity of SARS-CoV-2 and help in developing putative methods of diagnosis and treatment. Copyright 2020 Parlikar et al.

PeerJ

Understanding genomic diversity, pan-genome, and evolution of SARS-CoV-2

The development of multicellularity is a key evolutionary transition allowing for differentiation of physiological functions across a cell population that confers survival benefits; among unicellular bacteria, this can lead to complex developmental behaviors and the formation of higher-order community structures. Herein, we demonstrate that in the social δ-proteobacterium Myxococcus xanthus, the secretion of a novel biosurfactant polysaccharide (BPS) is spatially modulated within communities, mediating swarm migration as well as the formation of multicellular swarm biofilms and fruiting bodies. BPS is a type IV pilus (T4P)-inhibited acidic polymer built of randomly acetylated β-linked tetrasaccharide repeats. Both BPS and exopolysaccharide (EPS) are produced by dedicated Wzx/Wzy-dependent polysaccharide-assembly pathways distinct from that responsible for spore-coat assembly. While EPS is preferentially produced at the lower-density swarm periphery, BPS production is favored in the higher-density swarm interior; this is consistent with the former being known to stimulate T4P retraction needed for community expansion and a function for the latter in promoting initial cell dispersal. Together, these data reveal the central role of secreted polysaccharides in the intricate behaviors coordinating bacterial multicellularity. Copyright: © 2020 Islam et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Fulltext

PLoS Biology

Modulation of bacterial multicellularity via spatio-specific polysaccharide secretion

Artificial water channels are synthetic molecules that aim to mimic the structural and functional features of biological water channels (aquaporins). Here we report on a cluster-forming organic nanoarchitecture, peptide-appended hybrid[4]arene (PAH[4]), as a new class of artificial water channels. Fluorescence experiments and simulations demonstrated that PAH[4]s can form, through lateral diffusion, clusters in lipid membranes that provide synergistic membrane-spanning paths for a rapid and selective water permeation through water-wire networks. Quantitative transport studies revealed that PAH[4]s can transport &gt;109 water molecules per second per molecule, which is comparable to aquaporin water channels. The performance of these channels exceeds the upper bound limit of current desalination membranes by a factor of ~104, as illustrated by the water/NaCl permeability–selectivity trade-off curve. PAH[4]’s unique properties of a high water/solute permselectivity via cooperative water-wire formation could usher in an alternative design paradigm for permeable membrane materials in separations, energy production and barrier applications. © 2019, The Author(s), under exclusive licence to Springer Nature Limited.

Nature Nanotechnology

Artificial water channels enable fast and selective water permeation through water-wire networks

We have encountered pancreatic tumors with unique histologic features, which do not conform to any of the known tumors of the pancreas or other anatomical sites. We aimed to define their clinicopathologic features and whether they are characterized by recurrent molecular signatures. Eight cases were identified; studied histologically and by immunohistochemistry. Selected cases were also subjected to whole-exome sequencing (WES; n = 4), RNA-sequencing (n = 6), Archer FusionPlex assay (n = 5), methylation profiling using the Illumina MethylationEPIC (850k) array platform (n = 6), and TERT promoter sequencing (n = 5). Six neoplasms occurred in females. The mean age was 43 years (range: 26–75). Five occurred in the head/neck of the pancreas. All patients were treated surgically; none received neoadjuvant/adjuvant therapy. All patients are free of disease after 53 months of median follow-up (range: 8–94). The tumors were well-circumscribed, and the median size was 1.8 cm (range: 1.3–5.8). Microscopically, the unencapsulated tumors had a geographic pattern of epithelioid cell nests alternating with spindle cell fascicles. Some areas showed dense fibrosis, in which enmeshed tumor cells imparted a slit-like pattern. The predominant epithelioid cells had scant cytoplasm and round-oval nuclei with open chromatin. The spindle cells displayed irregular, hyperchromatic nuclei. Mitoses were rare. No lymph node metastases were identified. All tumors were positive for vimentin, CD99 and cytokeratin (patchy), while negative for markers of solid pseudopapillary neoplasm, neuroendocrine, acinar, myogenic/rhabdoid, vascular, melanocytic, or lymphoid differentiation, gastrointestinal stromal tumor as well as MUC4. Whole-exome sequencing revealed no recurrent somatic mutations or amplifications/homozygous deletions in any known oncogenes or tumor suppressor genes. RNA-sequencing and the Archer FusionPlex assay did not detect any recurrent likely pathogenic gene fusions. Single sample gene set enrichment analysis revealed that these tumors display a likely mesenchymal transcriptomic program. Unsupervised analysis (t-SNE) of their methylation profiles against a set of different mesenchymal neoplasms demonstrated a distinct methylation pattern. Here, we describe pancreatic neoplasms with unique morphologic/immunophenotypic features and a distinct methylation pattern, along with a lack of abnormalities in any of key genetic drivers, supporting that these neoplasms represent a novel entity with an indolent clinical course. Given their mesenchymal transcriptomic features, we propose the designation of “sclerosing epithelioid mesenchymal neoplasm” of the pancreas. © 2019, United States & Canadian Academy of Pathology.

Modern Pathology

Sclerosing epithelioid mesenchymal neoplasm of the pancreas – a proposed new entity

Lipid membranes, enveloping all living systems, are of crucial importance, and control over their structure and composition is a highly desirable functionality of artificial structures. However, the rational design of protein-inspired systems is still challenging. Here we have developed a highly functional nucleic acid construct that self-assembles and inserts into membranes, enabling lipid transfer between inner and outer leaflets. By designing the structure to account for interactions between the DNA, its hydrophobic modifications, and the lipids, we successfully exerted control over the rate of interleaflet lipid transfer induced by our DNA-based enzyme. Furthermore, we can regulate the level of lipid transfer by altering the concentration of divalent ions, similar to stimuli-responsive lipid-flipping proteins. © 2020 American Chemical Society.

Nano Letters

Tailoring Interleaflet Lipid Transfer with a DNA-based Synthetic Enzyme

Nutcracker syndrome is a rare vascular disorder that involves compression of the left renal vein (LRV), most often at the level of the aortomesenteric angle. In some cases, this compression syndrome arises in the setting of unusual vascular anatomic variants. We describe the case of a 43-year-old woman with a duplicated inferior vena cava who was found to have LRV compression on magnetic resonance angiography and venography with intravascular ultrasound. The patient was successfully treated with concurrent transposition of the LRV and left-sided inferior vena cava, with complete resolution of symptoms. © 2020 The Authors

Journal of Vascular Surgery Cases and Innovative Techniques

Anterior nutcracker syndrome in the setting of a duplicated inferior vena cava

Turmoil of petroleum oil prices, energy, and environmental security, and its finite sources has made biodiesel a more attractive renewable fuel. Biodiesel, a mixture of fatty acid methyl esters (FAMEs) is conventionally derived from either vegetable oils or animal fats. However, using these conventional sources has raised food security concerns and their succinct supply can serve only for a small fraction of existing demand for transport fuels. Furthermore, the cost and acreages needed for the production of vegetable oils has impeded its use as a feedstock and necessitated to look for an alternative feedstock. Recently, much emphasis has been laid on oleaginous microorganisms for their ability to synthesize lipids under stress conditions. In comparison to vegetable oils, microbial oils have many dividends, such as short life cycle, less industrious, less land requirement, independent of season and climate, and easier to scale-up. This chapter attempts to focus light on recent research on oleaginous yeast, mold, bacteria, and microalgae as prospective oil resources for biodiesel production in the near future. In addition, the biochemistry of lipid accumulation, lipid enhancement via biochemical, metabolic and transcription factor engineering approaches, and fermentation processes have been discussed. © Springer Nature India Private Limited 2020.