BITS Faculty Publications

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    Emerging relationship between the gut microbiota and neurodegenerative disorders
    (Springer, 2024-08) Marathe, Sandhya Amol; Tare, Meghana
    A growing body of evidence indicates that the multitude of organisms residing in our gut can profoundly affect our health. These organisms are loosely termed as gut microbiota and have been known to affect the function as well as the behavioral aspects of human health. Recent research shows that the microorganisms in our gut play a crucial role in determining our health and susceptibility to disease. Newly identified intricacies of connection between nervous system and gut microbiota are specially intriguing, since nervous system intersects and in a manner regulates almost every other function of the body. Interestingly, gut microbiota has been found to be affected in cases of nervous system disorders, including neurodegeneration, such as but not limited to Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and multiple sclerosis. The number of people worldwide with neurodegenerative disorders grows yearly, but effective treatments with few side effects remain limited. There is a new avenue of translational research, which evaluates the gut-brain-microbiome axis for management and therapeutic ideas for neurodegenerative disorders. It is therefore important to understand the newer intervention techniques using microbiota, which can be employed for holistic cure of neurodegenerative disorders. This chapter encompasses a comprehensive review of the relationship between gut microbiota in the context of specific neurodegenerative disorders.
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    Non-apoptotic enteroblast-specific role of the initiator caspase Dronc for development and homeostasis of the Drosophila intestine
    (Springer Nature, 2021-01) Tare, Meghana
    The initiator caspase Dronc is the only CARD-domain containing caspase in Drosophila and is essential for apoptosis. Here, we report that homozygous dronc mutant adult animals are short-lived due to the presence of a poorly developed, defective and leaky intestine. Interestingly, this mutant phenotype can be significantly rescued by enteroblast-specific expression of dronc+ in dronc mutant animals, suggesting that proper Dronc function specifically in enteroblasts, one of four cell types in the intestine, is critical for normal development of the intestine. Furthermore, enteroblast-specific knockdown of dronc in adult intestines triggers hyperplasia and differentiation defects. These enteroblast-specific functions of Dronc do not require the apoptotic pathway and thus occur in a non-apoptotic manner. In summary, we demonstrate that an apoptotic initiator caspase has a very critical non-apoptotic function for normal development and for the control of the cell lineage in the adult midgut and therefore for proper physiology and homeostasis.
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    Animal models in the study of Alzheimer's disease and Parkinson's disease: A historical perspective
    (Wiley, 2022-01) Tare, Meghana
    Alzheimer's disease and Parkinson's disease are two of the most prevalent and disabling neurodegenerative diseases globally. Both are proteinopathic conditions and while occasionally inherited, are largely sporadic in nature. Although the advances in our understanding of the two have been significant, they are far from complete and neither diagnosis nor the current practices in treatment and rehabilitation is adequately helpful. Animal models have historically found application as testing beds for novel therapeutics and continue to be valuable aids in pharmacological research. This review chronicles the development of those models in the context of Alzheimer's and Parkinson's disease, and highlights the shifting paradigms in studying two human-specific conditions in non-human organisms.
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    Editorial: Protein misfolding, altered mechanisms and neurodegeneration
    (Frontiers, 2023-02) Tare, Meghana
    Neurodegenerative diseases (NDs) like Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), Frontotemporal lobe degeneration (FTLD), Polyglutamine diseases such as Huntington's disease (HD), Spinocerebellar ataxias (SCAs) etc., are a group of debilitating disorders that affects millions of people worldwide and have no cure to-date. Despite the advancement in our understanding of molecular and genetic mechanisms underlying these NDs, only a limited symptom-based treatment options are available. As the life expectancy increases there is an increase in the number of ND patients, which will seriously challenge the availability of resources and will impact a nation's economy. There is an urgent need to develop an affordable healthcare system and find effective treatment options to provide better clinical regimens to cure these diseases. NDs affect neurons, neuronal connections associated with memory, cognition, thinking, strength, sensation, movements, learning, co-ordination, and other abilities. Although the causative factors of NDs varies from one to another and the differences in the disease symptoms could be many, these diseases share some common features. One of the common pathological hallmarks among the most NDs is aggregation or deposition of misfolded proteins. Compelling evidence from neuropathological, genetic, animal models studies, and other approaches have strongly supported the fact that accumulation of misfolded protein aggregates triggers a series of detrimental events, which results in synaptic alterations, neuronal cell loss, and significantly contributes toward disease pathogenesis.
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    A Bird’s Eye View on Cellular Dynamics In Huntington’s Disease
    (Current Science, 2023) Tare, Meghana
    Huntington's chorea is a rare neurodegenerative disorder caused by the dominant inheritance of the mutated huntingtin gene, housing poly-CAG or polyglutamine repeats. It is characterized by a wide variety of symptoms ranging from chorea and hypokinetic movements to behavioural and cognitive decline, followed by dementia and inevitable death. Over the past 120 years, all available therapeutics have been for the symptomatic management of Huntington's disease (HD) and require supportive physiotherapy and counselling to maximize the efficacy of the treatment. Several animal models have been employed to help elucidate and decrypt the pathophysiology of the disease, and also screen potential therapeutic candidates. In the last few decades, a deeper understanding of the cellular and molecular dynamics associated with HD has helped shed light on the mechanisms involved in disease progression. Genetic intervention for early detection, spreading awareness about HD and its symptoms, and training professionals in the nuances of the disease condition can significantly improve the lifestyle of patients. This article aims at summarizing the complex pathogenesis of HD at the cellular level using various disease models and available therapeutics
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    Insights Into the Dynamics and Composition of Biofilm Formed by Environmental Isolate of Enterobacter cloacae
    (Frontiers, 2022-07) Jha, Prabhat Nath; Tare, Meghana
    Bacterial biofilms are clinically admissible and illustrate an influential role in infections, particularly those related to the implant of medical devices. The characterization of biofilms is important to understand the etiology of the diseases. Enterobacter cloacae are known for causing infections by forming biofilms on various abiotic surfaces, such as medical devices. However, a detailed characterization in terms of morphology and the molecular composition of the formed biofilms by this bacterium is sparse. The present study provides insights into the biofilm formation of E. cloacae SBP-8, an environmental isolate, on various surfaces. We performed assays to understand the biofilm-forming capability of the SBP-8 strain and characterized the adhering potential of the bacteria on the surface of different medical devices (foley latex catheter, enteral feeding tube, and glass) at different temperatures. We found that medical devices exhibited strong colonization by E. cloacae SBP-8. Using field emission-scanning electron microscopy (FE-SEM) studies, we characterized the biofilms as a function of time. It indicated stronger biofilm formation in terms of cellular density and EPS production on the surfaces. Further, we characterized the biofilm employing surface-enhanced Raman spectroscopy (SERS) and identified the vast heterogenic nature of the biofilm-forming molecules. Interestingly, we also found that this heterogeneity varies from the initial stages of biofilm formation until the maturation and dispersion. Our studies provide insights into biofilm composition over a period of time, which might aid in understanding the biofilm dispersion phases, to enhance the presently available treatment strategies.
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    Characterization of functional amyloid curli in biofilm formation of an environmental isolate Enterobacter cloacae SBP-8. Antonie Van Leeuwenhoek
    (Springer, 2023-05) Jha, Prabhat Nath; Tare, Meghana
    The biofilm formation by bacteria is a complex process that is strongly mediated by various genetic and environmental factors. Biofilms contribute to disease infestation, especially in chronic infections. It is, therefore important to understand the factors affecting biofilm formation. This study reports the role of a functional amyloid curli in biofilm formation at various abiotic surfaces, including medical devices, by an environmental isolate of Enterobacter cloacae (SBP-8) which has been known for its pathogenic potential. A knockout mutant of csgA, the gene encoding the major structural unit of curli, was created to study the effect of curli on biofilm formation by E. cloacae SBP-8. Our findings confirm the production of curli at 25 °C and 37 °C in the wild-type strain. We further investigated the role of curli in the attachment of E. cloacae SBP-8 to glass, enteral feeding tube, and foley latex catheter. Contrary to the previous studies reporting the curli production below 30 °C in the majority of biofilm-forming bacterial species, we observed its production in E. cloacae SBP-8 at 37 °C. The formation of more intense biofilm in wild-type strain on various surfaces compared to curli-deficient strain (ΔcsgA) at both 25 °C and 37 °C suggested a prominent role of curli in biofilm formation. Further, electron and confocal microscopy studies demonstrated the formation of diffused monolayers of microbial cells on the abiotic surfaces by ΔcsgA strain as compared to the thick biofilm by respective wild-type strain, indicating the involvement of curli in biofilm formation by E. cloacae SBP-8. Overall, our findings provide insight into biofilm formation mediated by curli in E. cloacae SBP-8. Further, we show that it can be expressed at a physiological temperature on all surfaces, thereby indicating the potential role of curli in pathogenesis
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    COVID-19 infection and metabolic comorbidities: Mitigating role of nutritional sufficiency and drug – nutraceutical combinations of vitamin D
    (Elsevier, 2023-03) Deepa, P. R.; Tare, Meghana
    The vulnerability of human health is amplified in recent times with global increase in non-communicable diseases (due to lifestyle changes and environmental insults) and infectious diseases (caused by newer pathogens and drug-resistance strains). Clinical management of diseases is further complicated by disease severity caused by other comorbid factors. Drug-based therapy may not be the sole approach, particularly in scenarios like the COVID-19 pandemic, where there is no specific drug against SARS-CoV-2. Nutritional interventions are significant in armouring human populations in disease prevention, and as adjunctive therapy for disease alleviation. Amidst ongoing clinical trials to determine the efficacy of Vit. D against infections and associated complications, this review examines the pleiotropic benefits of nutritional adequacy of vitamin D (Vit. D) in combating viral infections (COVID-19), its severity and complications due to co-morbidities (obesity, diabetes, stroke and Kawasaki disease), based on research findings and clinical studies. Supplements of Vit. D in combination with other nutrients, and drugs, are suggested as promising preventive-health and adjunct-treatment strategies in the clinical management of viral infections with metabolic comorbidities.
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    Observing surface topography of Drosophila eye by Scanning Electron Microscopy
    (IAS, 2021) Tare, Meghana
    The compound eyes of Drosophila have been widely used since the beginning of fly genetics because of convenience of identifying visible mutants that affect eye development and morphology (Hales et al., 2015). Molecular genetic studies have provided detailed understanding of the diverse cascades of signaling pathways that bring about the remarkably organized arrays of ommatidia seen in adult eyes. Since nearly 75% protein-coding genes share high similarity between fly and human genomes (Pandey, 2011), fly has become a very good model for many human diseases, including the diverse neurodegenerative disorders. The GAL4-UAS binary system (see Chapters 31, 32) directed ectopic expression of transgenes, carrying mutant alleles causing human neurodegenerative disorders, in developing eyes of Drosophila, and examination of the adult eye surface as a morphological readout for neurodegeneration have been widely used to understand the events underlying neurodegeneration