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

Visceral leishmaniasis (VL) is a deadly neglected tropical disease that poses a serious problem in various countries all over the world. Implementation of various intervention strategies fail in controlling the spread of this disease due to issues of parasite drug resistance and resistance of sandfly vectors to insecticide sprays. Due to this, policy makers need to develop novel strategies or resort to a combination of multiple intervention strategies to control the spread of the disease. To address this issue, we propose an extensive SIR-type model for anthroponotic visceral leishmaniasis transmission with seasonal fluctuations modeled in the form of periodic sandfly biting rate. Fitting the model for real data reported in South Sudan, we estimate the model parameters and compare the model predictions with known VL cases. Using optimal control theory, we study the effects of popular control strategies namely, drug-based treatment of symptomatic and PKDL-infected individuals, insecticide treated bednets and spray of insecticides on the dynamics of infected human and vector populations. We propose that the strategies remain ineffective in curbing the disease individually, as opposed to the use of optimal combinations of the mentioned strategies. Testing the model for different optimal combinations while considering periodic seasonal fluctuations, we find that the optimal combination of treatment of individuals and insecticide sprays perform well in controlling the disease for the time period of intervention introduced. Performing a cost-effective analysis we identify that the same strategy also proves to be efficacious and cost-effective. Finally, we suggest that our model would be helpful for policy makers to predict the best intervention strategies for specific time periods and their appropriate implementation for elimination of visceral leishmaniasis. © 2017 Biswas 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.

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Fulltext

PLoS ONE

Optimal combinations of control strategies and cost-effective analysis for visceral leishmaniasis disease transmission

Biofuels are the imperative commodities influential in future bioeconomy that can be made sustainable by utilizing hemicelluloses which are the primary unutilized residues obtained from a lignocellulosic ethanol refinery. The abundant fraction in these hemicelluloses include pentoses (mainly xylose). The rationale behind the huge loss of hemicellulosic fraction is their heteropolymeric nature, low fermentability, lack of pentose specific transporters and enzyme cascades required for pentose fermentation by natural yeast strains. These lacunae lead to lower overall yield and productivity of ethanol thus rendering the entire process uneconomical. However, improvements in the conventional cellulose to ethanol know-how can trigger evolution towards bioeconomy. For industrial implementation of process technology, hemicellulosic stream should be integrated as a primary fraction along with celluloses for converting into ethanol. Thus, a novel hexose and pentose co-fermenting yeast strain is essential for a consolidated bioprocess aiming to achieve process economization. Considering a range of value added platform chemicals other than ethanol, such as xylitol, sorbitol, furfurals, hydroxyl methyl furfurals, ethylene glycol, glycolic acid, acetic acid, acetone, ethylene, and other residual biomass based products, such as biomanure, can render the biofuel production process more economical as multiple products may be obtained from the same biomass making the production process a comprehensive one. Therefore, the present review showcases the various technical impediments, breakthroughs, and bioeconomic aspects in the field of pentose to ethanol research which are instrumental in the future of the biofuel sector to address escalating oil prices and diminishing oil reserves. © 2016 Informa UK Limited, trading as Taylor & Francis Group.

Biofuels

Bioconversion of hemicelluloses of lignocellulosic biomass to ethanol: an attempt to utilize pentose sugars

Human macrophage phagolysosome and sandfly midgut provide antagonistic ecological niches for Leishmania parasites to survive and proliferate. Parasites optimize their metabolism to utilize the available inadequate resources by adapting to those environments. Lately, a number of metabolomics studies have revived the interest to understand metabolic strategies utilized by the Leishmania parasite for optimal survival within its hosts. For the first time, we propose a reconstructed genome-scale metabolic model for Leishmania infantum JPCM5, the analyses of which not only captures observations reported by metabolomics studies in other Leishmania species but also divulges novel features of the L. infantum metabolome. Our results indicate that Leishmania metabolism is organized in such a way that the parasite can select appropriate alternatives to compensate for limited external substrates. A dynamic non-essential amino acid motif exists within the network that promotes a restricted redistribution of resources to yield required essential metabolites. Further, subcellular compartments regulate this metabolic re-routing by reinforcing the physiological coupling of specific reactions. This unique metabolic organization is robust against accidental errors and provides a wide array of choices for the parasite to achieve optimal survival. © 2017 The Author(s).

Scientific Reports

Revealing the mystery of metabolic adaptations using a genome scale model of Leishmania infantum

Escalating demand for novel biocatalysts has intensified the production of vital enzymes from microbial, plant and animal origins. Microbial sources are mostly preferred owing to their short doubling time, capacity to utilize a wide range of substrates and easy maintenance. Enzymes have a crucial role in biorefiner ies mainly due to their ability to operate under mild conditions and substrate specificity, which enables efficient raw material biotransformation with low/no inhibitor formation, thus manifesting higher product yield. In this milieu, utili zation of recalcitrant lignocellulosic feedstocks may be considered as a sustain able alternative for fuel production. Enzymatic pretreatment and hydrolysis of lignocellulosics is being increasingly pursued globally for biofuel production with an objective to alleviate the disadvantages caused by physical, chemical and physicochemical approaches on the yield of the product, process economy and environment. Therefore, this chapter focuses on the industrially imperative micro bial enzymes and their applications in biorefineries for eco-friendly lignocellulosic fuel production. © 2018 John Wiley & Sons, Inc.

Lignocellulosic Production and Industrial Applications

Microbial enzymes and lignocellulosic fuel production

Family Cystobacteraceae is a group of eubacteria within order Myxococcales and class Deltaproteobacteria that includesmore than 20 species belonging to 6 genera, that is, Angiococcus, Archangium, Cystobacter, Hyalangium, Melittangium, and Stigmatella. Earlier these members have been classified based on chitin degrading efficiency such as Cystobacter fuscus and Stigmatella aurantiaca, which are efficient chitin degraders, C. violaceus a partial chitin degrader and Archangium gephyra a chitin nondegrader. Here we report the 12.5 Mbp complete genome of A. gephyra DSM 2261T and compare it with four available genomes within the family Cystobacteraceae. Phylogeny and DNA-DNA hybridization studies reveal that A. gephyra is closest to Angiococcus disciformis, C. violaceus and C. ferrugineus, which are partial chitin degraders of the family Cystobacteraceae. Homology studies reveal the conservation of approximately half of the proteins in these genomes, with about 15% unique proteins in each genome. The total carbohydrate-active enzymes (CAZome) analysis reveals the presence of one GH18 chitinase in the A. gephyra genome whereas eight copies are present in C. fuscus and S. aurantiaca. Evolutionary studies of myxobacterial GH18 chitinases reveal that most of them are likely related to Terrabacteria and Proteobacteria whereas the Archangium GH18 homolog shares maximum similarity with those of chitin nondegrading Acidobacteria. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Genome Biology and Evolution

Unravelling the complete genome of Archangium gephyra DSM 2261T and evolutionary insights into myxobacterial chitinases

Aims: Cardiomyocyte β2-adrenergic receptor (β2AR) cyclic adenosine monophosphate (cAMP) signalling is regulated by the receptors’ subcellular location within transverse tubules (T-tubules), via interaction with structural and regulatory proteins, which form a signalosome. In chronic heart failure (HF), β2ARs redistribute from T-tubules to the cell surface, which disrupts functional signalosomes and leads to diffuse cAMP signalling. However, the functional consequences of structural changes upon β2AR-cAMP signalling during progression from hypertrophy to advanced HF are unknown. Methods and results: Rat left ventricular myocytes were isolated at 4-, 8-, and 16-week post-myocardial infarction (MI), β2ARs were stimulated either via whole-cell perfusion or locally through the nanopipette of the scanning ion conductance microscope. cAMP release was measured via a Förster Resonance Energy Transfer-based sensor Epac2-camps. Confocal imaging of di-8-ANNEPS-stained cells and immunoblotting were used to determine structural alterations. At 4-week post-MI, T-tubule regularity, density and junctophilin-2 (JPH2) expression were significantly decreased. The amplitude of local β2AR-mediated cAMP in T-tubules was reduced and cAMP diffused throughout the cytosol instead of being locally confined. This was accompanied by partial caveolin-3 (Cav-3) dissociation from the membrane. At 8-week post-MI, the β2AR-mediated cAMP response was observed at the T-tubules and the sarcolemma (crest). Finally, at 16-week post-MI, the whole cell β2AR-mediated cAMP signal was depressed due to adenylate cyclase dysfunction, while overall Cav-3 levels were significantly increased and a substantial portion of Cav-3 dissociated into the cytosol. Overexpression of JPH2 in failing cells in vitro or AAV9.SERCA2a gene therapy in vivo did not improve β2AR-mediated signal compartmentation or reduce cAMP diffusion. Conclusion: Although changes in T-tubule structure and β2AR-mediated cAMP signalling are significant even at 4-week post-MI, progression to the HF phenotype is not linear. At 8-week post-MI the loss of β2AR-mediated cAMP is temporarily reversed. Complete disorganization of β2AR-mediated cAMP signalling due to changes in functional receptor localization and cellular structure occurs at 16-week post-MI. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Cardiology.

Cardiovascular Research

T-tubule remodelling disturbs localized β2-adrenergic signalling in rat ventricular myocytes during the progression of heart failure

Prediction of essential genes helps to identify a minimal set of genes that are absolutely required for the appropriate functioning and survival of a cell. The available machine learning techniques for essential gene prediction have inherent problems, like imbalanced provision of training datasets, biased choice of the best model for a given balanced dataset, choice of a complex machine learning algorithm, and data-based automated selection of biologically relevant features for classification. Here, we propose a simple support vector machine-based learning strategy for the prediction of essential genes in Escherichia coli K-12 MG1655 metabolism that integrates a non-conventional combination of an appropriate sample balanced training set, a unique organism-specific genotype, phenotype attributes that characterize essential genes, and optimal parameters of the learning algorithm to generate the best machine learning model (the model with the highest accuracy among all the models trained for different sample training sets). For the first time, we also introduce flux-coupled metabolic subnetwork-based features for enhancing the classification performance. Our strategy proves to be superior as compared to previous SVM-based strategies in obtaining a biologically relevant classification of genes with high sensitivity and specificity. This methodology was also trained with datasets of other recent supervised classification techniques for essential gene classification and tested using reported test datasets. The testing accuracy was always high as compared to the known techniques, proving that our method outperforms known methods. Observations from our study indicate that essential genes are conserved among homologous bacterial species, demonstrate high codon usage bias, GC content and gene expression, and predominantly possess a tendency to form physiological flux modules in metabolism. © 2017 The Royal Society of Chemistry.

Molecular BioSystems

An integrative machine learning strategy for improved prediction of essential genes in Escherichia coli metabolism using flux-coupled features

Objective Length of stay fails to completely capture the clinical and economic effects of patient progression through the phases of inpatient care, such as admission, room placement, procedures, and discharge. Delayed hospital throughput has been linked to increased time spent in the emergency department and postanesthesia care unit, delayed time to treatment, increased in-hospital mortality, decreased patient satisfaction, and lost hospital revenue. We identified barriers to vascular surgery inpatient care progression and instituted defined measures to positively impact standardized metrics. Methods The study was divided into three periods: preintervention, “wash-in,” and postintervention. During the preintervention phase, barriers to patient flow were quantified by an interdisciplinary team. Suboptimal provider communication emerged as the key barrier. An enhanced communication intervention consisting of face-to-face and mobile application-based education on key patient flow metrics, explicit discussion of individual patient barriers to progression at rounds and interdisciplinary huddles, and communication of projected discharge and potential barriers via e-mail was developed with input from all stakeholders. Following a 4-week wash-in implementation phase, data collection was repeated. Results The pre- and postintervention patient cohorts accounted for 244.3 and 238.1 inpatient days, respectively. Both groups had similar baseline demographic, clinical characteristics, and procedures performed during hospitalization. The postintervention group was discharged 78 minutes earlier (14:00:32 vs 15:18:37; P = .03) with a trend toward increased discharge by noon (94% vs 88%; P = .09). Readmission rates did not differ (P = .44). Conclusions Implementation of a focused, interdisciplinary, frontline provider-driven, enhanced communication program can be feasibly incorporated into existing specialty surgical workflow. The program resulted in improved timeliness of discharge and projected cost savings, without increasing readmission rates. © 2016 Society for Vascular Surgery

Journal of Vascular Surgery

Systematic identification and management of barriers to vascular surgery patient discharge time of day

Background: Innovation has been a central focus of the Department of Surgery at the Brigham and Women's Hospital since its very inception. Here we review examples of innovations originating in this Department and analyze factors that have been critical to successful innovation. Finally, we discuss challenges to sustainability of innovation in this Department. Methods: Narrative review of the literature, interviews, and personal observations. Results: Examples of innovations reviewed here were each dependent on three critical elements: 1) multidisciplinary collaboration among surgical innovators and individuals outside of surgery who offered complementary skills and expertise, 2) a rich institutional environment that sustained a diverse complement of innovators working in close proximity, and 3) Department Chairmen who facilitated the work of innovators and promoted their contributions, rather than seeking personal prestige or financial gain. Contemporary challenges to sustainability of innovation include the prevailing emphasis on clinical efficiency and on cost containment. Conclusion: We have identified factors critical to successful innovation in a Department of Surgery. The relevance of these factors is unlikely to be diminished, even in the changing landscape of modern medicine. © Copyright 2017, Mary Ann Liebert, Inc. 2017.

Journal of Laparoendoscopic and Advanced Surgical Techniques

A Century of Surgical Innovation at a Boston Hospital

GAC repeat expansion from five to seven in the exonic region of the gene for cartilage oligomeric matrix protein (COMP) leads to pseudoachondroplasia, a skeletal abnormality. However, the molecular mechanism by whichGACexpansions in the COMP gene lead to skeletal dysplasias is poorly understood. Here we used molecular dynamics simulations, which indicate that an A . . .Amismatch in a d(GAC)6.d(GAC)6 duplex induces negative supercoiling, leading to a local B-to-Z DNA transition. This transition facilitates the binding of d(GAC)7.d(GAC)7 with the Zα-binding domain of human adenosine deaminase acting on RNA 1 (ADAR1, hZαADAR1), as confirmed by CD, NMR, and microscale thermophoresis studies. The CD results indicated that hZαADAR1 recognizes the zigzag backbone of d(GAC)7. d(GAC)7 at the B-Z junction and subsequently converts it into Z-DNA via the so-called passive mechanism. Molecular dynamics simulations carried out for the modeled hZαADAR1- d(GAC)6.d(GAC)6 complex confirmed the retention of previously reported important interactions between the two molecules. These findings suggest that hZαADAR1 binding with the GAC hairpin stem in COMP can lead to a non-genetic, RNA editing- mediated substitution in COMP that may then play a crucial role in the development of pseudoachondroplasia. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Journal of Biological Chemistry

A B-Z junction induced by an A . . . A mismatch in GAC repeats in the gene for cartilage oligomeric matrix protein promotes binding with the HzαADAR1protein