Neha Sirwani

Bio: Neha Sirwani is an academic researcher from Indian Institute of Science. The author has contributed to research in topics: Histone code & Onchocerca volvulus. The author has an hindex of 1, co-authored 1 publications receiving 13 citations.

Synthesising environmental, epidemiological, and genetic data to assist decision making for onchocerciasis elimination

Abstract: Background: Population genetics is crucial for understanding the transmission dynamics of diseases like onchocerciasis. Landscape genetics identifies the ecological features that impact genetic variation between sampling sites. Here, we have used a landscape genetics framework to understand the relationship between environmental features and gene flow of the filarial parasite Onchocerca volvulus and of its intermediate host and vector, blackflies in the genus Simulium. We analysed samples from the ecological transition region separating the savannah and forest ecological regions of Ghana, where the transmission of O.volvulus has persisted despite almost half a century of onchocerciasis control efforts. Methods: We generated a baseline microfilarial prevalence map from the point estimates of pre-ivermectin microfilarial prevalence from 47 locations in the study area. We analysed mitochondrial data from 164 parasites and 93 blackflies collected from 15 communities and four breeding sites, respectively. We estimated population genetic diversity and identified correlations with environmental variables. Finally, we compared baseline prevalence maps to movement suitability maps that were based on significant environmental variables. Results: We found that the resistance surfaces derived from elevation (r = 0.793, p = 0.005) and soil moisture (r = 0.507, p = 0.002) were significantly associated with genetic distance between parasite sampling locations. Similarly, for the vector populations, the resistance surfaces derived from soil moisture (r = 0.788, p = 0.0417) and precipitation (r = 0.835, p = 0.0417) were significant. The correlation between the baseline parasite prevalence map and the parasite resistance surface map was stronger than the correlation between baseline prevalence and the vector resistance surface map. The central parts of the transition region which were conducive for both the parasite and the vector gene flow were most strongly associated with high baseline onchocerciasis prevalence. Conclusions: We present a framework for incorporating environmental, genetic, and prevalence data for identifying when ecological conditions are favourable for onchocerciasis transmission between communities. We identified areas with higher suitability for parasite and vector gene flow, which ultimately might help us gain deeper insights into defining transmission zones for onchocerciasis. Furthermore, this framework is translatable to other onchocerciasis endemic areas and to other vector-borne diseases.

Marine Environmental Epigenetics.

Abstract: Marine organisms' persistence hinges on the capacity for acclimatization and adaptation to the myriad of interacting environmental stressors associated with global climate change. In this context, epigenetics-mechanisms that facilitate phenotypic variation through genotype-environment interactions-are of great interest ecologically and evolutionarily. Our comprehensive review of marine environmental epigenetics guides our recommendations of four key areas for future research: the dynamics of wash-in and wash-out of epigenetic effects, the mechanistic understanding of the interplay of different epigenetic marks and the interaction with the microbiome, the capacity for and mechanisms of transgenerational epigenetic inheritance, and the evolutionary implications of the interaction of genetic and epigenetic features. Emerging insights in marine environmental epigenetics can be applied to critical issues such as aquaculture, biomonitoring, and biological invasions, thereby improving our ability to explain and predict the responses of marine taxa to global climate change.

Coral epigenetic responses to nutrient stress: Histone H2A.X phosphorylation dynamics and DNA methylation in the staghorn coral Acropora cervicornis.

Abstract: Nutrient pollution and thermal stress constitute two of the main drivers of global change in the coastal oceans. While different studies have addressed the physiological effects and ecological consequences of these stressors in corals, the role of acquired modifications in the coral epigenome during acclimatory and adaptive responses remains unknown. The present work aims to address that gap by monitoring two types of epigenetic mechanisms, namely histone modifications and DNA methylation, during a 7-week-long experiment in which staghorn coral fragments (Acropora cervicornis) were exposed to nutrient stress (nitrogen, nitrogen + phosphorus) in the presence of thermal stress. The major conclusion of this experiment can be summarized by two main results: First, coral holobiont responses to the combined effects of nutrient enrichment and thermal stress involve the post-translational phosphorylation of the histone variant H2A.X (involved in responses to DNA damage), as well as nonsignificant modifications in DNA methylation trends. Second, the reduction in H2A.X phosphorylation (and the subsequent potential impairment of DNA repair mechanisms) observed after prolonged coral exposure to nitrogen enrichment and thermal stress is consistent with the symbiont-driven phosphorus limitation previously observed in corals subject to nitrogen enrichment. The alteration of this epigenetic mechanism could help to explain the synergistic effects of nutrient imbalance and thermal stress on coral fitness (i.e., increased bleaching and mortality) while supporting the positive effect of phosphorus addition to improving coral resilience to thermal stress. Overall, this work provides new insights into the role of epigenetic mechanisms during coral responses to global change, discussing future research directions and the potential benefits for improving restoration, management and conservation of coral reef ecosystems worldwide.

Environmental Epigenomics and Its Applications in Marine Organisms

Abstract: Although epigenetics is still a relatively new discipline, its development during the last 10 years has revolutionized the current understanding of genome structure and function. The present chapter provides an insight on the exciting field of environmental epigenetics (i.e., the cause-effect relationships between environmental signals and epigenetic modifications altering phenotypes) and its potential applications for different types of studies in the marine environment. In the first part of this chapter, this work focuses on defining epigenetics, the different mechanisms involved in the epigenetic regulation of gene expression, as well as their potential role during the evolution of life on Earth. In the second part, this chapter moves into the potential applications of epigenetics in marine organisms, using current research projects on model species ranging from marine invertebrates to large marine megafauna as references. Overall, the present contribution underscores the importance of environmental epigenetic studies in marine organisms to better understand how organisms respond to their surrounding environment, fostering the development of a new generation of biomarkers enhancing restoration, conservation, and management efforts.

Cellular and Molecular Mechanisms of Hydra Regeneration.

Abstract: Regeneration of lost body parts is essential to regain the fitness of the organism for successful living. In the animal kingdom, organisms from different clades exhibit varied regeneration abilities. Hydra is one of the few organisms that possess tremendous regeneration potential, capable of regenerating complete organism from small tissue fragments or even from dissociated cells. This peculiar property has made this genus one of the most invaluable model organisms for understanding the process of regeneration. Multiple studies in Hydra led to the current understanding of gross morphological changes, basic cellular dynamics, and the role of molecular signalling such as the Wnt signalling pathway. However, cell-to-cell communication by cell adhesion, role of extracellular components such as extracellular matrix (ECM), and nature of cell types that contribute to the regeneration process need to be explored in depth. Additionally, roles of developmental signalling pathways need to be elucidated to enable more comprehensive understanding of regeneration in Hydra. Further research on cross communication among extracellular, cellular, and molecular signalling in Hydra will advance the field of regeneration biology. Here, we present a review of the existing literature on Hydra regeneration biology and outline the future perspectives.

Epigenomic landscape of enhancer elements during Hydra head organizer formation

Abstract: Axis patterning during development is accompanied by large-scale gene expression changes. These are brought about by changes in the histone modifications leading to dynamic alterations in chromatin architecture. The cis regulatory DNA elements also play an important role towards modulating gene expression in a context-dependent manner. Hydra belongs to the phylum Cnidaria where the first asymmetry in the body plan was observed and the oral-aboral axis originated. Wnt signaling has been shown to determine the head organizer function in the basal metazoan Hydra. To gain insights into the evolution of cis regulatory elements and associated chromatin signatures, we ectopically activated the Wnt signaling pathway in Hydra and monitored the genome-wide alterations in key histone modifications. Motif analysis of putative intergenic enhancer elements from Hydra revealed the conservation of bilaterian cis regulatory elements that play critical roles in development. Differentially regulated enhancer elements were identified upon ectopic activation of Wnt signaling and found to regulate many head organizer specific genes. Enhancer activity of many of the identified cis regulatory elements was confirmed by luciferase reporter assay. Quantitative chromatin immunoprecipitation analysis upon activation of Wnt signaling further confirmed the enrichment of H3K27ac on the enhancer elements of Hv_Wnt5a, Hv_Wnt11 and head organizer genes Hv_Bra1, CnGsc and Hv_Pitx1. Additionally, perturbation of the putative H3K27me3 eraser activity using a specific inhibitor affected the ectopic activation of Wnt signaling indicating the importance of the dynamic changes in the H3K27 modifications towards regulation of the genes involved in the head organizer activity. The activation-associated histone marks H3K4me3, H3K27ac and H3K9ac mark chromatin in a similar manner as seen in bilaterians. We identified intergenic cis regulatory elements which harbor sites for key transcription factors involved in developmental processes. Differentially regulated enhancers exhibited motifs for many zinc-finger, T-box and ETS related TFs whose homologs have a head specific expression in Hydra and could be a part of the pioneer TF network in the patterning of the head. The ability to differentially modify the H3K27 residue is critical for the patterning of Hydra axis revealing a dynamic acetylation/methylation switch to regulate gene expression and chromatin architecture.