Molecular Interactions between Pathogens and the Circadian Clock

Barik, Sailen

doi:10.3390/ijms20235824

Cited by 14 publications

(15 citation statements)

References 122 publications

(227 reference statements)

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“…Taking this aspect into account, we addressed the association of DBP with circadian transcriptional regulation of tissue-specific processes in mammalian species, in the context of AAT. Especially our findings implicating the functional relationship of circadian control with the immune system are well substantiated by Solis et al [ 31 ], Barik et al [ 32 ] and Scheiermann et al [ 33 ]. In reference to the study by Frank Hawking [ 34 ], in which he experimentally established the link between circadian rhythm and T. congolense infection in the blood of laboratory rodents, our findings also support the important role of the circadian rhythm in the AAT disease.…”

Section: Introductionsupporting

confidence: 84%

Computational Identification of Master Regulators Influencing Trypanotolerance in Cattle

Rajavel

Schmitt

Gültaş

2021

IJMS

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African Animal Trypanosomiasis (AAT) is transmitted by the tsetse fly which carries pathogenic trypanosomes in its saliva, thus causing debilitating infection to livestock health. As the disease advances, a multistage progression process is observed based on the progressive clinical signs displayed in the host’s body. Investigation of genes expressed with regular monotonic patterns (known as Monotonically Expressed Genes (MEGs)) and of their master regulators can provide important clue for the understanding of the molecular mechanisms underlying the AAT disease. For this purpose, we analysed MEGs for three tissues (liver, spleen and lymph node) of two cattle breeds, namely trypanosusceptible Boran and trypanotolerant N’Dama. Our analysis revealed cattle breed-specific master regulators which are highly related to distinguish the genetic programs in both cattle breeds. Especially the master regulators MYC and DBP found in this study, seem to influence the immune responses strongly, thereby susceptibility and trypanotolerance of Boran and N’Dama respectively. Furthermore, our pathway analysis also bolsters the crucial roles of these master regulators. Taken together, our findings provide novel insights into breed-specific master regulators which orchestrate the regulatory cascades influencing the level of trypanotolerance in cattle breeds and thus could be promising drug targets for future therapeutic interventions.

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Section: Introductionsupporting

confidence: 84%

Computational Identification of Master Regulators Influencing Trypanotolerance in Cattle

Rajavel

Schmitt

Gültaş

2021

IJMS

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“…Finally, there are many other peripheral areas of global warming that will also affect biological life, such as possible alterations of light intensity and circadian rhythm, and change of the environment from aerobic to anaerobic [ 158 , 159 , 160 , 161 ], which will add to the burden of selection.…”

Section: Prospects Of Mutational Survival In Global Warmingmentioning

confidence: 99%

Evolution of Protein Structure and Stability in Global Warming

Barik

2020

IJMS

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This review focuses on the molecular signatures of protein structures in relation to evolution and survival in global warming. It is based on the premise that the power of evolutionary selection may lead to thermotolerant organisms that will repopulate the planet and continue life in general, but perhaps with different kinds of flora and fauna. Our focus is on molecular mechanisms, whereby known examples of thermoresistance and their physicochemical characteristics were noted. A comparison of interactions of diverse residues in proteins from thermophilic and mesophilic organisms, as well as reverse genetic studies, revealed a set of imprecise molecular signatures that pointed to major roles of hydrophobicity, solvent accessibility, disulfide bonds, hydrogen bonds, ionic and π-electron interactions, and an overall condensed packing of the higher-order structure, especially in the hydrophobic regions. Regardless of mutations, specialized protein chaperones may play a cardinal role. In evolutionary terms, thermoresistance to global warming will likely occur in stepwise mutational changes, conforming to the molecular signatures, such that each “intermediate” fits a temporary niche through punctuated equilibrium, while maintaining protein functionality. Finally, the population response of different species to global warming may vary substantially, and, as such, some may evolve while others will undergo catastrophic mass extinction.

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“…A growing body of research supports the role of clock genes in regulating cytokines before and during infection [ 94 ]. In a reciprocal fashion, immune agents can impact the clock [ 95 ]. To investigate the interplay between the immune system and the circadian clock, we developed a mathematical model incorporating the bidirectional coupling between the lung circadian clock and the acute inflammatory response.…”

Section: Discussionmentioning

confidence: 99%

Modeling the circadian regulation of the immune system: Sexually dimorphic effects of shift work

Abo

2021

PLoS Comput Biol

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The circadian clock exerts significance influence on the immune system and disruption of circadian rhythms has been linked to inflammatory pathologies. Shift workers often experience circadian misalignment as their irregular work schedules disrupt the natural light-dark cycle, which in turn can cause serious health problems associated with alterations in genetic expressions of clock genes. In particular, shift work is associated with impairment in immune function, and those alterations are sex-specific. The goal of this study is to better understand the mechanisms that explain the weakened immune system in shift workers. To achieve that goal, we have constructed a mathematical model of the mammalian pulmonary circadian clock coupled to an acute inflammation model in the male and female rats. Shift work was simulated by an 8h-phase advance of the circadian system with sex-specific modulation of clock genes. The model reproduces the clock gene expression in the lung and the immune response to various doses of lipopolysaccharide (LPS). Under normal conditions, our model predicts that a host is more sensitive to LPS at circadian time (CT) CT12 versus CT0 due to a dynamic change of Interleukin 10 (IL-10), an anti-inflammatory cytokine. We identify REV-ERB as a key modulator of IL-10 activity throughout the circadian day. The model also predicts a reversal of the times of lowest and highest sensitivity to LPS, with males and females exhibiting an exaggerated response to LPS at CT0, which is countered by a blunted immune response at CT12. Overall, females produce fewer pro-inflammatory cytokines than males, but the extent of sequelae experienced by males and females varies across the circadian day. This model can serve as an essential component in an integrative model that will yield mechanistic understanding of how shift work-mediated circadian disruptions affect the inflammatory and other physiological responses.

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Molecular Interactions between Pathogens and the Circadian Clock

Cited by 14 publications

References 122 publications

Computational Identification of Master Regulators Influencing Trypanotolerance in Cattle

Computational Identification of Master Regulators Influencing Trypanotolerance in Cattle

Evolution of Protein Structure and Stability in Global Warming

Modeling the circadian regulation of the immune system: Sexually dimorphic effects of shift work

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