Department Of Biotechnology

IIT Madras is a public technical and research university located in Chennai, Tamil Nadu. Founded in 1959, it is recognised as an Institute of National Importance.

IIT Madras has been ranked as the top engineering institute in India for four years in a row by the National Institutional Ranking Framework of the MHRD

It currently offers undergraduate, postgraduate and research degrees across 16 disciplines in Engineering, Sciences, Humanities and Management. About 596 faculty belonging to science and engineering departments and centres of the Institute are engaged in teaching, research and industrial consultancy.

IIT Madras

Essential gene prediction models built so far are heavily reliant on sequence-based features, and the scope of network-based features has been narrow. Previous work from our group demonstrated the importance of using network-based features for predicting essential genes with high accuracy. Here, we apply our approach for the prediction of essential genes to organisms from the STRING database and host the results in a standalone website. Our database, NetGenes, contains essential gene predictions for 2,700+ bacteria predicted using features derived from STRING protein\textendash protein functional association networks. Housing a total of over 2.1 million genes, NetGenes offers various features like essentiality scores, annotations, and feature vectors for each gene. NetGenes database is available from https://rbc-dsai-iitm.github.io/NetGenes/.

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Department of Computer Science and Engineering

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Frontiers in Genetics

NetGenes: A Database of Essential Genes Predicted Using Features From Interaction Networks

Intrinsically disordered regions (IDRs) in proteins are characterized by their flexibilities and low complexity regions, which lack unique 3 D structures in solution. IDRs play a significant role in signaling, regulation, and binding multiple partners, including DNA, RNA, and proteins. Although various experiments have shown the role of disordered regions in binding with RNA, a detailed computational analysis is required to understand their binding and recognition mechanism. In this work, we performed molecular dynamics simulations of 10 protein–RNA complexes to understand the binding governed by intrinsically disordered regions. The simulation results show that most of the disordered regions are important for RNA-binding and have a transition from disordered-to-ordered conformation upon binding, which often contribute significantly towards the binding affinity. Interestingly, most of the disordered residues are present at the interface or located as a linker between two regions having similar movements. The DOT regions are overlaped or flanked with experimentally reported functionally important residues in the recognition of protein-RNA complexes. This study provides additional insights for understanding the role and recognition mechanism of disordered regions in protein–RNA complexes. Communicated by Ramaswamy H. Sarma. © 2021 Informa UK Limited, trading as Taylor &amp; Francis Group.

Journal of Biomolecular Structure and Dynamics

Understanding disorder-to-order transitions in protein–RNA complexes using molecular dynamics simulations

The traditional hydrogels are prone to break due to the applied stress. The deformation of the implanted hydrogels would result in the loss of structural integrity, leading to the failure of hydrogel functionalities and tissue regeneration. Self-healing hydrogels (AG-UPy), composed of oxidized alginate and ureidopyrimidinone-functionalized gelatin (G-UPy), were developed to address this challenge. These self-healing hydrogels possess two independent healing mechanisms, viz., Schiff base formation and UPy dimerization. These hydrogels were compared with oxidized alginate-gelatin (AG) hydrogels. AG-UPy hydrogels showed effective self-healing in a short time (about 2 min) after applying 800% strain, wherein recovery was not achieved with the AG hydrogel. However, the shear-thinning property of UPy made the AG-UPy hydrogel mechanically weaker than the AG hydrogel. To improve the mechanical strength of the AG-UPy hydrogel, we impregnated poly(ethylene glycol)-poly(urethane)/cloisite nanohybrid (PEG-PU/C) to prepare the AG-UPy/PEG-PU/C hydrogel. The incorporation of PEG-PU/C resulted in a 20-fold increase in the compression strength compared to that of the AG-UPy hydrogel. The AG-UPy/PEG-PU/C hydrogels also showed rapid self-healing. Incorporating the nanohybrid improved the cell proliferation by 2-and 1.25-fold compared to that of the AG and AG-UPy hydrogels, respectively. Therefore, PEG-PU/C combined with the UPy-functionalized polymer could be used to modulate mechanical strength and self-healing and enhance cell proliferation. © 2021 American Chemical Society.

ACS Applied Bio Materials

Nanohybrid-Reinforced Gelatin-Ureidopyrimidinone-Based Self-healing Injectable Hydrogels for Tissue Engineering Applications

In recent years, there has been an increasing focus on inorganic nanomaterials for various applications, such as catalysis, thermal energy storage, biomedical imaging, drug delivery, and tissue engineering. Amongst these, Mesoporous Silica Nanoparticles (MSNs) possess an orderly mesoporous structure, large surface area, and pore volume. Hence, MSNs have shown tremendous potential for drug delivery and tissue engineering. In this work, we have studied the potential of pure MSNs for bone tissue engineering applications. Our results show that MSNs were successfully synthesized using a modified sol-gel method. ATR-FTIR spectra, powder XRD pattern, and thermogravimetric analysis confirmed the physicochemical nature of the MSNs. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images reveal the orderly arrangement and size of the mesoporous structure. In vitro cytotoxicity assays performed using NIH/3T3 fibroblast cells and MG-63 osteosarcoma cells show the cytocompatibility of the synthesized pure MSNs. Furthermore, we confirmed the biocompatibility of the MSNs using in vivo zebrafish toxicity studies. Our results show that MSNs were biocompatible at concentrations as high as 1 mg/ml. Osteogenic activity of the synthesized MSNs were evaluated using alkaline phosphatase (ALP) activity and real-time PCR analysis for the period of 7 days. ALP activity and expression of the osteocalcin gene were significantly higher in the presence of MSNs. Alizarin Red S staining also confirmed the increased calcium mineral deposition in the presence of MSNs. The MSNs showed highest osteogenic activity at 1 mg/ml concentration. Using the chick chorioallantoic membrane assay, we have also shown that the MSNs exhibit proangiogenic activity. Our results show that in the presence of 1 mg/ml MSNs, the number of blood vessels was 3 to 4-fold higher than the control. Based on the in vitro and in vivo biocompatibility, osteogenic and proangiogenic activities, it is evident that these MSNs can serve as an ideal new generation biomaterial that can aid in vascularized bone formation. © 2020 Elsevier Inc.

Microporous and Mesoporous Materials

Evaluating the inherent osteogenic and angiogenic potential of mesoporous silica nanoparticles to augment vascularized bone tissue formation

The urgent need for a treatment of COVID-19 has left researchers with limited choice of either developing an effective vaccine or identifying approved/investigational drugs developed for other medical conditions for potential repurposing, thus bypassing long clinical trials. In this work, we compared the sequences of experimentally verified SARS-CoV-2 neutralizing antibodies and sequentially/structurally similar commercialized therapeutic monoclonal antibodies. We have identified three therapeutic antibodies, Tremelimumab, Ipilimumab and Afasevikumab. Interestingly, these antibodies target CTLA4 and IL17A, levels of which have been shown to be elevated during severe SARS-CoV-2 infection. The candidate antibodies were evaluated further for epitope restriction, interaction energy and interaction surface to gauge their repurposability to tackle SARS-CoV-2 infection. Our work provides candidate antibody scaffolds with dual activities of plausible viral neutralization and immunosuppression. Further, these candidate antibodies can also be explored in diagnostic test kits for SARS-CoV-2 infection. We opine that this in silico workflow to screen and analyze antibodies for repurposing would have widespread applications. © 2021, The Author(s).

Scientific Reports

Exploring antibody repurposing for COVID-19: beyond presumed roles of therapeutic antibodies

The field of tissue engineering is rapidly growing nowadays, and the development of the bio-functional scaffolds to mimic the natural environment of the body tissue to replace the damaged or diseased tissues. Use of nanomaterials to develop nanostructured biomaterial scaffolds showing enhanced biological functions than microstructured materials. Nanostructured materials have higher surface area and biomimetic nature, hence allow better cell adhesion than conventional materials, which is needed for materials used for tissue engineering applications. Unlike conventional materials, nanomaterials mimic resembling natural extracellular matrix (ECM) to support better protein adsorption and also stimulate enhanced tissue regeneration. Here, we address different categories of biomaterials used to fabricating nanostructured scaffolds for tissue regeneration applications. The desired properties required for various tissue engineering scaffolds and its methods of fabrication, current development, and future directions of these methodologies are discussed. In addition to that, the special emphasis is given on bone tissue engineering and three dimensional (3D printing) technologies to manufacture tissue engineering scaffolds using various nanomaterials are also discussed in this chapter. © The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2021.

Springer Series in Biomaterials Science and Engineering

Fabrication of nanostructured scaffolds for tissue engineering applications

Candida parapsilosisATCC 7330 supported gold nanoparticles (CpGNP), prepared by a simple and green method can selectively reduce nitroarenes and substituted nitroarenes with different functional groups like halides (-F, -Cl, -Br), olefins, esters and nitriles using sodium borohydride. The product aryl amines which are useful for the preparation of pharmaceuticals, polymers and agrochemicals were obtained in good yields (up to >95%) using CpGNP catalyst under mild conditions. The catalyst showed high recyclability (≥10 cycles) and is a robust free flowing powder, stored and used after eight months without any loss in catalytic activity. © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2021.

New Journal of Chemistry

Yeast supported gold nanoparticles: an efficient catalyst for the synthesis of commercially important aryl amines

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are well-known neuronal degenerative disorders that share common pathological events. Approved medications alleviate symptoms but do not address the root cause of the disease. Energy dysfunction in the neuronal population leads to various pathological events and ultimately results in neuronal death. Identifying common therapeutic targets for these disorders may help in the drug discovery process. The Brodmann area 9 (BA9) region is affected in both the disease conditions and plays an essential role in cognitive, motor, and memory-related functions. Analyzing transcriptome data of BA9 provides deep insights related to common pathological pathways involved in AD and PD. In this work, we map the preprocessed BA9 fastq files generated by RNA-seq for disease and control samples with reference hg38 genomic assembly and identify common variants and differentially expressed genes (DEG). These variants are predominantly located in the 3′ UTR (non-promoter) region, affecting the conserved transcription factor (TF) binding motifs involved in the methylation and acetylation process. We have constructed BA9-specific functional interaction networks, which show the relationship between TFs and DEGs. Based on expression signature analysis, we propose that MAPK1, VEGFR1/FLT1, and FGFR1 are promising drug targets to restore blood-brain barrier functionality by reducing neuroinflammation and may save neurons. © Copyright © 2021 Dharshini, Jemimah, Taguchi and Gromiha.

Exploring Common Therapeutic Targets for Neurodegenerative Disorders Using Transcriptome Study

Microbial communities that metabolise pentose and hexose sugars are useful in producing high-value chemicals, resulting in the effective conversion of raw materials to the product, a reduction in the production cost, and increased yield. Here, we present a computational analysis approach called CAMP (Co-culture/Community Analyses for Metabolite Production) that simulates and identifies appropriate communities to produce a metabolite of interest. To demonstrate this approach, we focus on the optimal production of lactate from various Lactic Acid Bacteria. We used genome-scale metabolic models (GSMMs) belonging to Lactobacillus, Leuconostoc, and Pediococcus species from the Virtual Metabolic Human (VMH; https://vmh.life/) resource and well-curated GSMMs of L. plantarum WCSF1 and L. reuteri JCM 1112. We analysed 1176 two-species communities using a constraint-based modelling method for steady-state flux-balance analysis of communities. Flux variability analysis was used to detect the maximum lactate flux in the communities. Using glucose or xylose as substrates separately or in combination resulted in either parasitism, amensalism, or mutualism being the dominant interaction behaviour in the communities. Interaction behaviour between members of the community was deduced based on variations in the predicted growth rates of monocultures and co-cultures. Acetaldehyde, ethanol, acetate, among other metabolites, were found to be cross-fed between community members. L. plantarum WCSF1 was found to be a member of communities with high lactate yields. In silico community optimisation strategies to predict reaction knock-outs for improving lactate flux were implemented. Reaction knock-outs of acetate kinase, phosphate acetyltransferase, and fumarate reductase in the communities were found to enhance lactate production. © 2021 The Author(s)

Computational and Structural Biotechnology Journal

Two-species community design of Lactic Acid Bacteria for optimal production of Lactate

Underlying every living cell, there is a beautifully concerted circuitry of signalling, metabolism and regulation that, together, orchestrate a variety of functions. Synthetic biology has targeted this circuitry at all levels, engineering it towards a wide array of applications – but also expanding our understanding fundamental aspects of the cell. Fuelled by advances in DNA sequencing, synthesis, editing, and computational modelling and circuit design, synthetic biology has broken tremendous ground in the last decade all across the world