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The Role of Signalling, Transcriptional and Noncoding RNAs Networks in Morphogenesis, Tissue Homeostasis and Regeneration

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: closed (30 June 2021) | Viewed by 17379

Special Issue Editors

Prof. Dr. Julio Vera-González

E-Mail Website
Guest Editor
Department of Dermatology, Faculty of Medicine, University Hospital Erlangen and Friedrich-Alexander University Erlangen-Nürnberg, 91052 Erlangen, Germany
Interests: cancer systems biology; systems immunology; systems neurobiology; network biology; ncRNA regulation; multilevel modelling; computational modeling in drug target discovery
Dr. Xin Lai

E-Mail Website
Guest Editor
Laboratory of Systems Tumor Immunology, Department of Dermatology, Universitätsklinikum Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany
Interests: medical systems biology; bioinformatics; biomathematics; network biology; noncoding RNA
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear colleagues,

At the molecular level, tissue organization during development, homeostasis, and degeneration is controlled by a myriad of biomolecules, including signalling proteins, transcription factors, and noncoding RNAs. These molecules do not exert their control of cell phenotypes in isolation but through densely interconnected biochemical networks. The purpose of this Special Issue is to provide an overview of the current knowledge about the molecular networks underlying the regulation of cells during development and regeneration, but also how they lose functionality in tissue damage and degeneration. We expect reviews about the use of genomics, as well as network and systems biology in different domains of developmental biology and tissue engineering. Additionally, we expect scientific reports presenting bioinformatics, network and systems biology methodologies, databases, and tools, in the context of development and tissue regeneration. Finally, we look for scientific contributions illustrating the capabilities of these methodologies in context-relevant case studies and how they can combine experimental work with cellular and animal models, or with data from patient cohorts in case of degenerative diseases.

Assoc. Prof. Julio Vera-González
Dr. Xin Lai
Guest Editors

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Keywords

  • Morphogenesis
  • Tissue engineering
  • Degenerative diseases
  • Genome organization
  • Functional genomics
  • Epigenomics
  • Bioinformatics
  • Gene–gene, protein–protein, TF-ncRNA and metabolic network reconstruction and analysis
  • Computational modelling of biological networks
  • Computational modelling of morphogene gradients
  • DNA-Seq, RNA-Seq, and ChIP-Seq
  • Single cell sequencing
  • Gene expression.

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Published Papers (5 papers)

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Research

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14 pages, 3957 KiB  
Article
Dimensional Changes in Lipid Rafts from Human Brain Cortex Associated to Development of Alzheimer’s Disease. Predictions from an Agent-Based Mathematical Model
by Guido Santos and Mario Díaz
Int. J. Mol. Sci. 2021, 22(22), 12181; https://doi.org/10.3390/ijms222212181 - 10 Nov 2021
Cited by 2 | Viewed by 1852
Abstract
Alzheimer’s disease (AD) is a neurodegenerative disease caused by abnormal functioning of critical physiological processes in nerve cells and aberrant accumulation of protein aggregates in the brain. The initial cause remains elusive—the only unquestionable risk factor for the most frequent variant of the [...] Read more.
Alzheimer’s disease (AD) is a neurodegenerative disease caused by abnormal functioning of critical physiological processes in nerve cells and aberrant accumulation of protein aggregates in the brain. The initial cause remains elusive—the only unquestionable risk factor for the most frequent variant of the disease is age. Lipid rafts are microdomains present in nerve cell membranes and they are known to play a significant role in the generation of hallmark proteinopathies associated to AD, namely senile plaques, formed by aggregates of amyloid β peptides. Recent studies have demonstrated that human brain cortex lipid rafts are altered during early neuropathological phases of AD as defined by Braak and Braak staging. The lipid composition and physical properties of these domains appear altered even before clinical symptoms are detected. Here, we use a coarse grain molecular dynamics mathematical model to predict the dimensional evolution of these domains using the experimental data reported by our group in human frontal cortex. The model predicts significant size and frequency changes which are detectable at the earliest neuropathological stage (ADI/II) of Alzheimer’s disease. Simulations reveal a lower number and a larger size in lipid rafts from ADV/VI, the most advanced stage of AD. Paralleling these changes, the predictions also indicate that non-rafts domains undergo simultaneous alterations in membrane peroxidability, which support a link between oxidative stress and AD progression. These synergistic changes in lipid rafts dimensions and non-rafts peroxidability are likely to become part of a positive feedback loop linked to an irreversible amyloid burden and neuronal death during the evolution of AD neuropathology. Full article
(This article belongs to the Special Issue The Role of Signalling, Transcriptional and Noncoding RNAs Networks in Morphogenesis, Tissue Homeostasis and Regeneration)
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16 pages, 3305 KiB  
Article
The Role of Age, Neutrophil Infiltration and Antibiotics Timing in the Severity of Streptococcus pneumoniae Pneumonia. Insights from a Multi-Level Mathematical Model Approach
by Guido Santos and Julio Vera
Int. J. Mol. Sci. 2020, 21(22), 8428; https://doi.org/10.3390/ijms21228428 - 10 Nov 2020
Cited by 3 | Viewed by 2168
Abstract
Bacterial pneumonia is one of the most prevalent infectious diseases and has high mortality in sensitive patients (children, elderly and immunocompromised). Although an infection, the disease alters the alveolar epithelium homeostasis and hinders normal breathing, often with fatal consequences. A special case is [...] Read more.
Bacterial pneumonia is one of the most prevalent infectious diseases and has high mortality in sensitive patients (children, elderly and immunocompromised). Although an infection, the disease alters the alveolar epithelium homeostasis and hinders normal breathing, often with fatal consequences. A special case is hospitalized aged patients, which present a high risk of infection and death because of the community acquired version of the Streptococcus pneumoniae pneumonia. There is evidence that early antibiotics treatment decreases the inflammatory response during pneumonia. Here, we investigate mechanistically this strategy using a multi-level mathematical model, which describes the 24 first hours after infection of a single alveolus from the key signaling networks behind activation of the epithelium to the dynamics of the local immune response. With the model, we simulated pneumonia in aged and young patients subjected to different antibiotics timing. The results show that providing antibiotics to elderly patients 8 h in advance compared to young patients restores in aged individuals the effective response seen in young ones. This result suggests the use of early, probably prophylactic, antibiotics treatment in aged hospitalized people with high risk of pneumonia. Full article
(This article belongs to the Special Issue The Role of Signalling, Transcriptional and Noncoding RNAs Networks in Morphogenesis, Tissue Homeostasis and Regeneration)
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Review

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18 pages, 932 KiB  
Review
Alveolar Regeneration in COVID-19 Patients: A Network Perspective
by Shishir K. Gupta, Mugdha Srivastava, Rashmi Minocha, Aman Akash, Seema Dangwal and Thomas Dandekar
Int. J. Mol. Sci. 2021, 22(20), 11279; https://doi.org/10.3390/ijms222011279 - 19 Oct 2021
Cited by 8 | Viewed by 4164
Abstract
A viral infection involves entry and replication of viral nucleic acid in a host organism, subsequently leading to biochemical and structural alterations in the host cell. In the case of SARS-CoV-2 viral infection, over-activation of the host immune system may lead to lung [...] Read more.
A viral infection involves entry and replication of viral nucleic acid in a host organism, subsequently leading to biochemical and structural alterations in the host cell. In the case of SARS-CoV-2 viral infection, over-activation of the host immune system may lead to lung damage. Albeit the regeneration and fibrotic repair processes being the two protective host responses, prolonged injury may lead to excessive fibrosis, a pathological state that can result in lung collapse. In this review, we discuss regeneration and fibrosis processes in response to SARS-CoV-2 and provide our viewpoint on the triggering of alveolar regeneration in coronavirus disease 2019 (COVID-19) patients. Full article
(This article belongs to the Special Issue The Role of Signalling, Transcriptional and Noncoding RNAs Networks in Morphogenesis, Tissue Homeostasis and Regeneration)
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16 pages, 1222 KiB  
Review
The Potential of OMICs Technologies for the Treatment of Immune-Mediated Inflammatory Diseases
by Charles Gwellem Anchang, Cong Xu, Maria Gabriella Raimondo, Raja Atreya, Andreas Maier, Georg Schett, Vasily Zaburdaev, Simon Rauber and Andreas Ramming
Int. J. Mol. Sci. 2021, 22(14), 7506; https://doi.org/10.3390/ijms22147506 - 13 Jul 2021
Cited by 7 | Viewed by 4401
Abstract
Immune-mediated inflammatory diseases (IMIDs), such as inflammatory bowel diseases and inflammatory arthritis (e.g., rheumatoid arthritis, psoriatic arthritis), are marked by increasing worldwide incidence rates. Apart from irreversible damage of the affected tissue, the systemic nature of these diseases heightens the incidence of cardiovascular [...] Read more.
Immune-mediated inflammatory diseases (IMIDs), such as inflammatory bowel diseases and inflammatory arthritis (e.g., rheumatoid arthritis, psoriatic arthritis), are marked by increasing worldwide incidence rates. Apart from irreversible damage of the affected tissue, the systemic nature of these diseases heightens the incidence of cardiovascular insults and colitis-associated neoplasia. Only 40–60% of patients respond to currently used standard-of-care immunotherapies. In addition to this limited long-term effectiveness, all current therapies have to be given on a lifelong basis as they are unable to specifically reprogram the inflammatory process and thus achieve a true cure of the disease. On the other hand, the development of various OMICs technologies is considered as “the great hope” for improving the treatment of IMIDs. This review sheds light on the progressive development and the numerous approaches from basic science that gradually lead to the transfer from “bench to bedside” and the implementation into general patient care procedures. Full article
(This article belongs to the Special Issue The Role of Signalling, Transcriptional and Noncoding RNAs Networks in Morphogenesis, Tissue Homeostasis and Regeneration)
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Graphical abstract

16 pages, 2007 KiB  
Review
Mathematical Modelling in Biomedicine: A Primer for the Curious and the Skeptic
by Julio Vera, Christopher Lischer, Momchil Nenov, Svetoslav Nikolov, Xin Lai and Martin Eberhardt
Int. J. Mol. Sci. 2021, 22(2), 547; https://doi.org/10.3390/ijms22020547 - 7 Jan 2021
Cited by 11 | Viewed by 3935
Abstract
In most disciplines of natural sciences and engineering, mathematical and computational modelling are mainstay methods which are usefulness beyond doubt. These disciplines would not have reached today’s level of sophistication without an intensive use of mathematical and computational models together with quantitative data. [...] Read more.
In most disciplines of natural sciences and engineering, mathematical and computational modelling are mainstay methods which are usefulness beyond doubt. These disciplines would not have reached today’s level of sophistication without an intensive use of mathematical and computational models together with quantitative data. This approach has not been followed in much of molecular biology and biomedicine, however, where qualitative descriptions are accepted as a satisfactory replacement for mathematical rigor and the use of computational models is seen by many as a fringe practice rather than as a powerful scientific method. This position disregards mathematical thinking as having contributed key discoveries in biology for more than a century, e.g., in the connection between genes, inheritance, and evolution or in the mechanisms of enzymatic catalysis. Here, we discuss the role of computational modelling in the arsenal of modern scientific methods in biomedicine. We list frequent misconceptions about mathematical modelling found among biomedical experimentalists and suggest some good practices that can help bridge the cognitive gap between modelers and experimental researchers in biomedicine. This manuscript was written with two readers in mind. Firstly, it is intended for mathematical modelers with a background in physics, mathematics, or engineering who want to jump into biomedicine. We provide them with ideas to motivate the use of mathematical modelling when discussing with experimental partners. Secondly, this is a text for biomedical researchers intrigued with utilizing mathematical modelling to investigate the pathophysiology of human diseases to improve their diagnostics and treatment. Full article
(This article belongs to the Special Issue The Role of Signalling, Transcriptional and Noncoding RNAs Networks in Morphogenesis, Tissue Homeostasis and Regeneration)
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