Computational Prediction of Potential Vaccine Candidates From tRNA Encoded peptides (tREP) Using a Bioinformatic Workflow and Molecular Dynamics Validations.

Transfer RNAs (tRNA) are non-coding RNAs. Encouraged by biological applications discovered for peptides derived from other non-coding genomic regions, we explore the possibility of deriving epitope-based vaccines from tRNA encoded peptides (tREP) in this study. Epitope-based vaccines have been identified as an effective strategy to mitigate safety and specificity concerns observed in vaccine development.

tREPs-A New Class of Functional tRNA-Encoded Peptides.

We asked if transfer RNA (tRNA) ever got an opportunity of translating its own sequence during evolution, what would have been the function of such tRNA-encoded peptides (tREPs)? If not, could one artificially synthesize tREPs to study the corresponding functional outcomes? Here, we report a novel, first-in-the-class, chemically synthesized tREP-18 molecule originating from the tRNA sequence showing potent antileishmanial property. As a first step, tRNAs were computationally translated into peptide sequence equivalents and a database of full-length hypothetical tREPs was created. The tREP sequences were sent into sequence, structure, and energy filters to narrow down potential peptides for experimental validation.

Building Biofoundry India: challenges and path forward.

Biofoundry is a place where biomanufacturing meets automation. The highly modular structure of a biofoundry helps accelerate the design-build-test-learn workflow to deliver products fast and in a streamlined fashion. In this perspective, we describe our efforts to build Biofoundry India, where we see the facility add a substantial value in supporting research, innovation and entrepreneurship.

Highly potent anti-malarial activity of benzopyrano(4,3-b)benzopyran derivatives and interaction analysis with putative target lactate dehydrogenase.

Malaria infection caused by is majorly responsible for millions of deaths in humans every year. Moreover, a rapid increase in resistance to existing drugs has posed an urgent need for new anti-malarials. Herein, we report the highly potent anti-malarial activity of benzopyrano(4,3-b)benzopyran derivatives, inspired from naturally occurring dependensin against chloroquine (CQ) sensitive and resistant strains.

Association of miR-760 with cancer: An overview.

MicroRNAs (miRNAs) are small non-coding RNA molecules of around 22 nucleotides in length. They are crucially involved in the post transcriptional regulation and thus play a significant role in the modulation of different diseases. Several studies have suggested that miRNA expression is dysregulated in various cancers through different mechanisms and the dysregulated miRNA in return affects different cancer hallmarks including cell proliferation, cell death suppression, metastasis and angiogenesis.

miR-145 supports cancer cell survival and shows association with DDR genes, methylation pattern, and epithelial to mesenchymal transition.

Background: Despite several reports describing the dual role of miR-145 as an oncogene and a tumor suppressor in cancer, not much has been resolved and understood.

Method: In this study, the potential targets of miR-145 were identified bio-informatically using different target prediction tools. The identified target genes were validated in vitro by dual luciferase assay.

HYPO: A Database of Human Hypothetical Proteins.

Background: There are genes whose function remains obscure as they may not have similarities to known regions in the genome. Such known 'unknown' genes constituting the Open Reading Frames (ORF) that remain in the epigenome are termed as orphan genes and the proteins encoded by them but having no experimental evidence of translation are termed as 'Hypothetical Proteins' (HPs).

Objectives: We have enhanced our former database of Hypothetical Proteins (HP) in human (HypoDB) with added annotation, application programming interfaces and descriptive features.

Deciphering the role of microRNA - A step by step guide.

MicroRNAs (miRNAs), are small non-coding RNAs of approximately 22 nucleotides in length, playing an important role in regulating gene expression post-transcriptionally. Understanding the effect of miRNA regulation in a pathway-specific manner unravels the approaches adopted to apprehend biological mechanisms, the information, which is scanty for researchers, not primed already for miR related research. Here, we describe a quick perspective in 5 steps with probable approaches and assays at every level to unravel the specific role of a microRNA, miR-145a-5p, as an example.

Computational study of 'HUB' microRNA in human cardiac diseases.

MicroRNAs (miRNAs) are small non-coding RNAs ~22 nucleotides long that do not encode for proteins but have been reported to influence gene expression in normal and abnormal health conditions. Though a large body of scientific literature on miRNAs exists, their network level profile linking molecules with their corresponding phenotypes, is less explored. Here, we studied a network of 191 human miRNAs reported to play a role in 30 human cardiac diseases.

Novel group-based QSAR and combinatorial design of CK-1δ inhibitors as neuroprotective agents.

Background: Tar DNA binding protein 43 (TDP-43) hyperphosphorylation, caused by Casein kinase 1 (CK-1) protein isoforms, is associated with the onset and progression of Amyotrophic Lateral Sclerosis (ALS). Among the reported isoforms and splice variants of CK-1 protein superfamily, CK-1δ is known to phosphorylate different serine and threonine sites on TDP-43 protein in vitro and thus qualifies as a potential target for ALS treatment.

Results: The developed GQSAR (group based quantitative structure activity relationship) model displayed satisfactory statistical parameters for the dataset of experimentally reported N-Benzothiazolyl-2-Phenyl Acetamide derivatives.

Exploring the potential of genome editing CRISPR-Cas9 technology.

CRISPR-Cas9 is an RNA-mediated adaptive immune system that protects bacteria and archaea from viruses or plasmids. Herein we discuss the recent development of CRISPR-Cas9 into a key technology for genome editing, targeting, and regulation in a wide range of organisms and cell types. It requires a custom designed single guide-RNA (sgRNA), a Cas9 endonuclease, and PAM sequences in the target region.

Predicting stable functional peptides from the intergenic space of .

Expression of synthetic proteins from intergenic regions of and their functional association was recently demonstrated (Dhar et al. in J Biol Eng 3:2, 2009. doi:10.

In silico study of peptide inhibitors against BACE 1.

Peptides are increasingly used as inhibitors of various disease specific targets. Several naturally occurring and synthetically developed peptides are undergoing clinical trials. Our work explores the possibility of reusing the non-expressing DNA sequences to predict potential drug-target specific peptides.

Computational identification of novel microRNAs and their targets in the malarial vector, Anopheles stephensi.

MicroRNAs are a ~22 nucleotide small non-coding RNAs found in animals, plants and viruses. They regulate key cellular processes by enhancing, degrading or silencing protein coding targets. Currently most of the data on miRNA is available from Drosophila .

Heat stress-induced Cup9-dependent transcriptional regulation of SIR2.

The epigenetic writer Sir2 maintains the heterochromatin state of chromosome in three chromosomal regions, namely, the silent mating type loci, telomeres, and the ribosomal DNA (rDNA). In this study, we demonstrated the mechanism by which Sir2 is regulated under heat stress. Our study reveals that a transient heat shock causes a drastic reduction in the SIR2 transcript which results in sustained failure to initiate silencing for as long as 90 generations.

Decahydroquinolines from the venom of a formicinae ant, Oecophylla smaragdina.

Ecologically significant species in controlling pests, Oecophylla smaragdina uses its venom to paralyze their prey and to communicate with their colony mates. But no significant analysis of the ant's venom gland secretions has been carried out hitherto. This study describes the identification of venom constituents of Oecophylla smaragdina using coupled gas chromatography and mass spectroscopy (GC-MS) analysis.

Making novel proteins from pseudogenes.

Motivation: Recently, we made synthetic proteins from non-coding DNA of Escherichia coli. Encouraged by this, we asked: can we artificially express pseudogenes into novel and functional proteins? What kind of structures would be generated? Would these proteins be stable? How would the organism respond to the artificial reactivation of pseudogenes?

Results: To answer these questions, we studied 16 full-length protein equivalents of pseudogenes. The sequence-based predictions indicated interesting molecular and cellular functional roles for pseudogene-derived proteins.

Metabolic engineering of biosynthetic pathway for production of renewable biofuels.

Metabolic engineering is an important area of research that involves editing genetic networks to overproduce a certain substance by the cells. Using a combination of genetic, metabolic, and modeling methods, useful substances have been synthesized in the past at industrial scale and in a cost-effective manner. Currently, metabolic engineering is being used to produce sufficient, economical, and eco-friendly biofuels.

Looking for a sequence based allostery definition: a statistical journey at different resolution scales.

The aim of this work was to detect allosteric hotspots signatures characterizing protein regions acting as the 'key drivers' of global allosteric conformational change. We computationally estimated the relative strength of intra-molecular interaction in allosteric proteins between two putative allostery-susceptible sites using a co-evolution model based upon the optimization of the cross-correlation in terms of free-energy-transfer hydrophobicity scale (Tanford scale) distribution along the chain. Cross-Recurrence Quantification Analysis (Cross-RQA) applied on the sequences of allostery susceptible sites showed evidence of strong interaction amongst allosteric susceptible sites.

Sequence signatures of allosteric proteins towards rational design.

Allostery is the phenomenon of changes in the structure and activity of proteins that appear as a consequence of ligand binding at sites other than the active site. Studying mechanistic basis of allostery leading to protein design with predetermined functional endpoints is an important unmet need of synthetic biology. Here, we screened the amino acid sequence landscape in search of sequence-signatures of allostery using Recurrence Quantitative Analysis (RQA) method.

Building momentum for systems and synthetic biology in India.

Biological systems are inherently noisy. Predicting the outcome of a perturbation is extremely challenging. Traditional reductionist approach of describing properties of parts, vis-a-vis higher level behaviour has led to enormous understanding of fundamental molecular level biology.

Identification of hub proteins from sequence.

Identification of hub proteins from sequence is a challenge in molecular biology. Therefore, it is of interest to predict protein hubs in networks. We describe the prediction of protein "hub" using physiochemical, thermodynamic and conformational properties of amino acid residues in sequence.

Why so few drug targets: a mathematical explanation?

The apparently paradoxical lack of correlation between the huge increase in the discovery of new potential drug targets made possible by the post-genomic sciences and new drugs development has stimulated many different interpretations. Here we illustrate the general principle of redundancy of biological pathways on hand of simplified mathematical approaches applied to different models of biological regulation. The simulation was based on the analysis of the 'degree of autonomy' of network architectures in which the possibility for an external stimulus (e.

Laws of biology: why so few?

Finding fundamental organizing principles is the current intellectual front end of systems biology. From a hydrogen atom to the whole cell level, organisms manage massively parallel and massively interactive processes over several orders of magnitude of size. To manage this scale of informational complexity it is natural to expect organizing principles that determine higher order behavior.