Latest works (2026) by Ramakrishnan Sitaraman
Clinical and Molecular Epidemiology, 2026
Human polyomavirus 2 (JC virus) is a neurotropic virus that is ubiquitous in the human population... more Human polyomavirus 2 (JC virus) is a neurotropic virus that is ubiquitous in the human population, and most carriers remain asymptomatic for life. However immune suppression, whether natural or because of medication, can lead to virus activation often leading to the fatal condition of progressive multifocal leukoencephalopathy. This critical review provides a survey of the mechanisms of environmental transmission between hosts, the cellular and molecular biology of JC virus-host interactions, and the available therapeutic options-both approved and experimental. It also highlights gaps in our knowledge of the biology and pathogenesis of this virus, and the challenges involved in better understanding the mechanistic basis of JC virus reactivation as well as tailoring therapeutic strategies to different disease contexts. Finally, the available findings are interpreted within an ecologicalevolutionary (eco-evo) framework.
Death before dishonor at Gomolava?
Springer Nature Research Communities, 2026
Ongoing refinements in chronological frameworks describing the presence of Indo-European/Indic languages in the Indian subcontinent
European Journal of Human Genetics , 2026
Free full text available at: https://rdcu.be/e4Wd9
Science, 2026
This is an eLetter published in response to the research article by Carlson et al. published in S... more This is an eLetter published in response to the research article by Carlson et al. published in Science (doi: 10.1126/science.ady3571). In this letter, I draw attention to the potential role of other DNA-targeting microbial biomolecules such as DNases, DNA restriction endonucleases, DNA methyltransferases, and even DNA-binding proteins in contributing to genotoxicity and/or carcinogenesis. This hypothesis is supported by citations from the scientific literature, and I also provide brief suggestions on how it may be tested.
The absolute chronology of the presence of Indo-European/Indic languages in the Indian subcontinent.
Eur J Hum Genet, 2026
Free full text: https://rdcu.be/eYbuU
Science by Ramakrishnan Sitaraman
Subversion from Within and Without: Effector Molecule Transfer from Obligate Intracellular Apicomplexan Parasites to Human Host Cells
Intercellular and Interorganellar Transfer and Communication in Biology and Medicine., 2024
Intracellular protozoan pathogens have to negotiate the internal environment of the host cell the... more Intracellular protozoan pathogens have to negotiate the internal environment of the host cell they find themselves in, as well as manipulate the host cell to ensure their own survival, replication, and dissemination. The transfer of key effector molecules from the pathogen to the host cell is crucial to this interaction and is technically more demanding to study as compared to an extracellular pathogen. While several effector molecules have been identified, the mechanisms and conditions underlying their transfer to the host cell remain partly or entirely unknown. Improvements in experimental systems have revealed tantalizing details of such intercellular transfer, which form the subject of this chapter.
3 Biotech, 2023
The non-structural protein 5 (NS5) is the most conserved protein among flaviviruses, a family tha... more The non-structural protein 5 (NS5) is the most conserved protein among flaviviruses, a family that includes the dengue virus. It functions both as an RNA-dependent RNA polymerase and an RNA-methyltransferase and is therefore essential for the replication of viral RNA. The discovery that dengue virus NS5 protein (DENV-NS5) can also localize to the nucleus has resulted in renewed interest in its potential roles at the host-virus interface. In this study, we have used two complementary computational approaches in parallel – one based on linear motifs (ELM) and another based on tertiary structure of the protein (DALI) – to predict the host proteins that DENV-NS5 might interact with. Of the 42 human proteins predicted by both these methods, 34 are novel. Pathway analysis of these 42 human proteins shows that they are involved in key host cellular processes related to cell cycle regulation, proliferation, protein degradation, apoptosis, and immune responses. A focused analysis of transcription factors that directly interact with the predicted DENV-NS5 interacting proteins was performed, followed by the identification of downstream genes that are differentially expressed after dengue infection using previously published RNA-seq data. Our study provides unique insights into the DENV-NS5 interaction network and delineates mechanisms whereby DENV-NS5 could impact the host-virus interface. The novel interactors identified in this study could be potentially targeted by NS5 to modulate the host cellular environment in general, and the immune response in particular, thereby extending the role of DENV-NS5 beyond its known enzymatic functions.
The Open COVID Journal, 2021
In this perspective article, we suggest that bacterial quorum-sensing signal molecules (QSSMs) be... more In this perspective article, we suggest that bacterial quorum-sensing signal molecules (QSSMs) be systematically screened and evaluated for their ability to exert anti-inflammatory activity in the context of COVID-19-associated cytokine storms and other hyper-inflammatory conditions. Rapid and relevant in vitro screening of these and other compounds (natural or synthetic) can be accomplished by a careful choice of assay systems that are relevant to the disease context. Some lines of evidence indicating the utility of using such an approach, its potential benefits and risks during actual usage, as well as avenues for further research, are discussed.
Frontiers in Cellular and Infection Microbiology, 2021
Dengue is emerging as one of the most prevalent mosquito-borne viral diseases of humans. The 11kb... more Dengue is emerging as one of the most prevalent mosquito-borne viral diseases of humans. The 11kb RNA genome of the dengue virus encodes three structural proteins (envelope, pre-membrane, capsid) and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5), all of which are translated as a single polyprotein that is subsequently cleaved by viral and host cellular proteases at specific sites. Non-structural protein 5 (NS5) is the largest of the non-structural proteins, functioning as both an RNAdependent RNA polymerase (RdRp) that replicates the viral RNA and an RNA methyltransferase enzyme (MTase) that protects the viral genome by RNA capping, facilitating polyprotein translation. Within the human host, NS5 interacts with several proteins such as those in the JAK-STAT pathway, thereby interfering with anti-viral interferon signalling. This mini-review presents annotated, consolidated lists of known and potential NS5 interactors in the human host as determined by experimental and computational approaches respectively. The most significant protein interactors and the biological pathways they participate in are also highlighted and their implications discussed, along with the specific serotype of dengue virus as appropriate. This information can potentially stimulate and inform further research efforts towards providing an integrative understanding of the mechanisms by which NS5 manipulates the human-virus interface in general and the innate and adaptive immune responses in particular.
The Impact of Bacterial Quorum Sensing Signal Molecules on Animal Hosts: Paradigms and Perspectives
ACS Symposium Series, Vol. 1374, Quorum Sensing: Microbial Rules of Life, 2020
The Role of Constructive Neutral Evolution in the Development of Complexity from Symbioses: A Microbe-Centric View
Symbiosis: Cellular, Molecular, Medical and Evolutionary Aspects, 2020
Symbiogenesis presents the biologist with very different explanatory issues compared to the linea... more Symbiogenesis presents the biologist with very different explanatory issues compared to the lineal and selectionist view of evolution based on individual entities, whether genes, organisms or species. A key question is how the co-existence of two or more partners in close association during a given generation can ultimately be stabilized enough to be transmitted to the next, how the ensuing complexity is maintained and how this arrangement impacts the reproductive fitness of the collective over evolutionary time. In this chapter, we highlight some observations gleaned from the microbial world that could shed light on this problem if viewed within the framework of constructive neutral evolution.
Cureus, 2019
Eucalyptus oil (EO) and EO containing products are readily available worldwide over the counter a... more Eucalyptus oil (EO) and EO containing products are readily available worldwide over the counter as topical nasal decongestants, rubefacients, anti-pyretics, and anti-inflammatory agents. However, EO is poisonous when orally ingested, or otherwise internally administered, resulting in serious outcomes such as seizures, vomiting, drowsiness, and even death. In this case report, we describe emergency measures adopted in a suspected case of EO ingestion by a 17-month-old female infant. It was found that stomach washes with normal saline followed by the oral administration of ranitidine to prevent vomiting restored and maintained normalcy over a 24-hour period. We situate our experience within the Indian context and recommend that pediatricians and healthcare workers routinely and explicitly warn parents about the serious consequences of the incorrect usage of substances containing essential oils in general and EO in particular.
Frontiers in Microbiology, 2016
Mycobacterium tuberculosis H37Rv escapes host-generated stresses by entering a dormant persistent... more Mycobacterium tuberculosis H37Rv escapes host-generated stresses by entering a dormant persistent state. Activation of toxin-antitoxin modules is one of the mechanisms known to trigger such a state with low metabolic activity. M. tuberculosis harbors a large number of TA systems mostly located within discernible genomic islands. We have investigated the parDE2 operon of M. tuberculosis H37Rv encoding MParE2 toxin and MParD2 antitoxin proteins. The parDE2 locus was transcriptionally active from growth phase till late stationary phase in M. tuberculosis. A functional promoter located upstream of parD2 GTG start-site was identified by 5-RACE and lacZ reporter assay. The MParD2 protein transcriptionally regulated the P parDE2 promoter by interacting through Arg16 and Ser15 residues located in the N-terminus. In Escherichia coli, ectopic expression of MParE2 inhibited growth in early stages, with a drastic reduction in colony forming units. Live-dead analysis revealed that the reduction was not due to cell death alone but due to formation of viable but non-culturable cells (VBNCs) also. The toxic activity of the protein, identified in the C-terminal residues Glu98 and Arg102, was neutralized by the antitoxin MParD2, both in vivo and in vitro. MParE2 inhibited mycobacterial DNA gyrase and interacted with the GyrB subunit without affecting its ATPase activity. Introduction of parE2 gene in the heterologous M. smegmatis host prevented growth and colony formation by the transformed cells. An M. smegmatis strain containing the parDE2 operon also switched to a non-culturable phenotype in response to oxidative stress. Loss in colony-forming ability of a major part of the MParE2 expressing cells suggests its potential role in dormancy, a cellular strategy for adaptation to environmental stresses. Our study has laid the foundation for future investigations to explore the physiological significance of parDE2 operon in mycobacterial pathogenesis.
Frontiers in Microbiology
Restriction-modification (R-M) systems are widespread among prokaryotes and, depending on their t... more Restriction-modification (R-M) systems are widespread among prokaryotes and, depending on their type, may be viewed as selfish genetic elements that persist as toxin-antitoxin modules, or as cellular defense systems against phage infection that confer a selective advantage to the host bacterium. Studies in the last decade have made it amply clear that these two options do not exhaust the list of possible biological roles for R-M systems. Their presence in a cell may also have a bearing on other processes such as horizontal gene transfer and gene regulation. From genome sequencing and experimental data, we know that Bacillus anthracis encodes at least three methylation-dependent (typeIV) restriction endonucleases (RE), and an orphan DNA methyltransferase. In this article, we first present an outline of our current knowledge of R-M systems in B. anthracis. Based on available DNA sequence data, and on our current understanding of the functions of similar genes in other systems, we conclude with hypotheses on the possible roles of the three REs and the orphan DNA methyltransferase.
Microbiology, 2016
The response of Saccharomyces cerevisiae to osmotic stress, whether arising from environmental co... more The response of Saccharomyces cerevisiae to osmotic stress, whether arising from environmental conditions or physiological processes, has been intensively studied in the last two decades. The well-known high-osmolarity glycerol (HOG) signalling pathway that is induced in response to osmotic stress interacts with other signalling pathways such as the cell wall integrity and the target of rapamycin pathways. Osmotic balance is also maintained by the regulated opening and closing of channel proteins in both the cell membrane and intracellular organelles such as the vacuole. Additionally, environmental stresses, including osmotic shock, induce intracellular calcium signalling. Thus, adaptation to environmental stresses in general, and osmotic stress in particular, is dependent on the concerted action of components of multiple interacting pathways. In this review, we describe some of the major mechanisms and molecules involved in osmoregulation via pathways other than the high-osmolarity glycerol pathway and their known interactions with one another that have been discovered over the last two decades. Abbreviations: CWI, cell wall integrity; ER, endoplasmic reticulum; ESR, environmental stress response; GAAC, general amino acid control; HACS, high-affinity Ca 2+ influx system; HOG, high-osmolarity glycerol; LACS, low-affinity Ca 2+ influx system; MIP, major intrinsic protein; PKA, protein kinase A; PKC, protein kinase C; TM, transmembrane; TOR, target of rapamycin; TORC1, TOR complex 1; TORC2, target of rapamycin complex 2; TRPC, transient receptor protein channel. Three supplementary figures are available with the online Supplementary Material.
Frontiers in Plant Science, 2015
Frontiers in Microbiology, 2015
Frontiers in Microbiology, 2015
Helicobacter pylori, a gastric pathogen, is known to be associated with gastric and duodenal ulce... more Helicobacter pylori, a gastric pathogen, is known to be associated with gastric and duodenal ulcers, and is also a strong risk factor for the development of gastric cancer and lymphoma of the mucosal-associated lymphoid tissue. Ordinarily, this should make a strong case for its eradication at par with any other infectious disease. However, the unique biology of H. pylori and the complexity of its interactions with humans, its only known natural host, do not permit the recommendation of unambiguous preventive and therapeutic measures. Moreover, this organism has co-evolved with humans as a practically universal member of the natural gastric microbiota over at least 100,000 years. H. pylori persists for a lifetime in mostly asymptomatic hosts, and causes clinical disease only in a minority of infections. Therefore, its potential contribution to the maintenance of human immune homeostasis, as is the case with the better-studied members of the intestinal microbiota, is certainly worthy of serious investigation. In this paper, we summarize some interesting and often anecdotal data drawn from recent studies, and examine their significance in the context of the hygiene hypothesis. We also examine whether the lower incidence of gastric cancer over large parts of the world in spite of a high prevalence of infection (the Asian and African enigmas) may be re-interpreted in terms of the hygiene hypothesis. Finally, it is suggested that an evolutionary-ecological approach to the study of H. pylori infection may help in the formulation of strategies for the management of this infection. This may well be an infectious disease wherein medical interventions may have to be personalized to ensure optimal outcomes.
Indian Journal of Biotechnology
Synthetic organic colours that contain the azo group (-N=N-) are a major component of dyes widely... more Synthetic organic colours that contain the azo group (-N=N-) are a major component of dyes widely used in the textile and food processing industries. Given the ready availability of food colours, their modest cost and established safety profiles, we evaluated their suitability as tracking dyes for the gel electrophoresis of nucleic acids and proteins. We have tested 3 azo-based food colours, viz., Orange Red, Lemon Yellow and Bright Green, procured from local grocery stores for this purpose. The results are qualitatively comparable to those obtained using established methods of loading proteins and nucleic acids with the widely used dyes, bromophenol blue and xylene cyanol. This method entails no modification of current protocols for sample loading and gel electrophoresis. Use of these reagents that are 'commonly considered safe' and available at a fraction of the cost of equivalent analytical grade reagents would be advantageous in routine molecular biology procedures, especially in resourcelimited contexts.
Frontiers in Microbiology, 2014
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Latest works (2026) by Ramakrishnan Sitaraman
https://communities.springernature.com/posts/death-before-dishonor-at-gomolava
Science by Ramakrishnan Sitaraman