Ankush Bansal

Modular Design of Picroside-II Biosynthesis Deciphered through NGS Transcriptomes and Metabolic Intermediates Analysis in Naturally Variant Chemotypes of a Medicinal Herb, Picrorhiza kurroa

Picroside-II (P-II), an iridoid glycoside, is used as an active ingredient of various commercial herbal formulations available for the treatment of liver ailments. Despite this, the knowledge of P-II biosynthesis remains scarce owing to its negligence in Picrorhiza kurroa shoots which sets constant barrier for function validation experiments. In this study, we utilized natural variation for P-II content in stolon tissues of different P. kurroa accessions and deciphered its metabolic route by integrating metabolomics of intermediates with differential NGS transcriptomes. Upon navigating through high vs. low P-II content accessions (1.3–2.6%), we have established that P-II is biosynthesized via degradation of ferulic acid (FA) to produce vanillic acid (VA) which acts as its immediate biosynthetic precursor. Moreover, the FA treatment in vitro at 150 μM concentration provided further confirmation with 2-fold rise in VA content. Interestingly, the cross-talk between different compartments of P. kurroa, i.e., shoots and stolons, resolved spatial complexity of P-II biosynthesis and consequently speculated the burgeoning necessity to bridge gap between VA and P-II production in P. kurroa shoots. This work thus, offers a forward looking strategy to produce both P-I and P-II in shoot cultures, a step toward providing a sustainable production platform for these medicinal compounds via-à-vis relieving pressure from natural habitat of P. kurroa.

A novel miRNA analysis framework to analyze differential biological networks

For understanding complex biological systems, a systems biology approach, involving both the top-down and bottom-up analyses, is often required. Numerous system components and their connections are best characterised as networks, which are primarily represented as graphs, with several nodes connected at multiple edges. Inefficient network visualisation is a common problem related to transcriptomic and genomic datasets. In this article, we demonstrate an miRNA analysis framework with the help of Jatropha curcas healthy and disease transcriptome datasets, functioning as a pipeline derived from the graph theory universe, and discuss how the network theory, along with gene ontology (GO) analysis, can be used to infer biological properties and other important features of a network. Network profiling, combined with GO, correlation, and co-expression analyses, can aid in efficiently understanding the biological significance of pathways, networks, as well as a studied system. The proposed framework may help experimental and computational biologists to analyse their own data and infer meaningful biological information.

Tau Pathology: A Step Towards Understanding Neurodegenerative Disorders Network Complexity

A number of neurodegenerative disorders (NDs) are usually referred as tauopathies and characterized by the disappearance or disintegration of tau protein from microtubules. Alzheimer’s disease (AD), Pick’s disease (PiD), Parkinson’s disease (PD) are directly or indirectly associated with tauopathy. Tau is a protein which is usually associated with microtubule. Microtubules are the backbone of neurons, and tau provides a support to microtubule stability. Hyperphosphorylation of tau leads to its separation from microtubule, consequently forming neurofibrillary tangles and resulting in a condition of dementia. Therapeutic implication on tauopathy is symptomatic as there is no exact regulation mechanism known till date. This chapter helps in the comprehensive study of biomarkers and pathways involved in tauopathy to decipher the complexity of the system, resulting in candidate drug target for the management of NDs.

An integrative approach to develop computational pipeline for drug-target interaction network analysis

Understanding the general principles governing the functioning of biological networks is a major challenge of the current era. Functionality of biological networks can be observed from drug and target interaction perspective. All possible modes of operations of biological networks are confined by the interaction analysis. Several of the existing approaches in this direction, however, are data-driven and thus lack potential to be generalized and extrapolated to different species. In this paper, we demonstrate a systems pharmacology pipeline and discuss how the network theory, along with gene ontology (GO) analysis, co-expression analysis, module re-construction, pathway mapping and structure level analysis can be used to decipher important properties of biological networks with the aim to propose lead molecule for the therapeutic interventions of various diseases.

Publisher Correction: A novel miRNA analysis framework to analyze differential biological networks

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In silico screening of deleterious single nucleotide polymorphisms (SNPs) and molecular dynamics simulation of disease associated mutations in gene responsible for Oculocutaneous Albinism type 6 (OCA 6) disorder

Abstract Solute carrier family 24 member 5 (SLC24A5) is a gene that is associated with oculocutaneous albinism type 6 (OCA6) disorder and is involved in skin and hair pigmentation. It is involved in the maturation of melanosomes and melanin synthesis. SLC24A5 gene is located in the chromosomal position of 15q21.1. The present study involves the use of computational techniques in order to obtain a detailed picture of the most probable mutations that are associated with SLC24A5. From the observed result it was found that the mutation S145F is most deleterious and disease associated is predicted using several bioinformatics tools. The 3-D structures of native and mutant (S145F) were modeled in order to understand protein functionality using ab initio Robetta server. The modeled structure validation was done with ERRAT, Verify-3D, Procheck and RAMPAGE Ramachandran plot analysis. The most validated structure undergoes molecular dynamics simulations (MDS) study to understand the structural and functional behaviour of the native and mutant proteins. The MDS result showed the more flexibility in the native SLC24A5 structure. Due to mutation in the SLC24A5 protein structure it became more rigid and might disturb the conformational changes and glycosylation function of protein structure and might play role in inducing the OCA6. This study provides a significant insight into the underlying molecular mechanism involved in albinism associated with OCA6. It further helps scientists to develop a drug therapy against OCA 6 disease. Communicated by Ramaswamy H. Sarma

Uncovering interconnections between kinases vis-à-vis physiological and biochemical processes contributing to picroside-I biosynthesis in a medicinal herb, Picrorhiza kurroa Royle ex. Benth.

Picroside-I (P-I) is an iridoid glycoside of Picrorhiza kurroa, a perennial medicinal herb native to North-Western Himalayas, used in the preparation of herbal drug formulations. Natural habitat shoots (PKSS) produce significantly higher P-I content as compared to in vitro shoots (PKS-15 and PKS-25). Although temperature and culture conditions are known to play a major role in influencing P-I biosynthesis in different shoots of P. kurroa, the molecular mechanisms behind signal perception of variable environments are completely unknown. Kinases have been considered as key signaling proteins which control cellular processes involved in adaptability under diverse environments, thereby affecting downstream primary and secondary metabolic pathways. The current study investigated the association of kinases with P-I production and shoot biomass in P. kurroa. Transcriptome mining and in silico transcript abundance in three shoot tissues revealed differentially expressed kinases under high and low P-I accumulating conditions. A total of 521, 473 and 346 transcripts encoding kinases were identified in PKS-25, PKS-15 and PKSS tissues, respectively. Gene expression analysis of 43 selected genes in differential P-I content shoot tissues and genotypes revealed key processes regulated by kinases which might be associated with P-I biosynthesis. Expression of 16 kinases genes involved in plant–pathogen interactions, abiotic stress, wounding, hormonal response and carbohydrate metabolism was observed to be up-regulated in high P-I accumulating conditions, indicating their possible role in eliciting P-I biosynthesis in P. kurroa. Analysis of kinases along with genes involved in controlling shoot biomass productivity revealed that auxin response plays a major role in affecting biomass productivity in in vitro shoots of P. kurroa. This study provides a basic understanding of physiological processes affected under variable environmental conditions leading to differential biosynthesis of P-I in P. kurroa.