Systems Biology: New Paradigms for Cell Biology and Drug Design

Author(s):  
H. V. Westerhoff
2020 ◽  
Vol 17 (166) ◽  
pp. 20200013 ◽  
Author(s):  
Zoe Schofield ◽  
Gabriel N. Meloni ◽  
Peter Tran ◽  
Christian Zerfass ◽  
Giovanni Sena ◽  
...  

The last five decades of molecular and systems biology research have provided unprecedented insights into the molecular and genetic basis of many cellular processes. Despite these insights, however, it is arguable that there is still only limited predictive understanding of cell behaviours. In particular, the basis of heterogeneity in single-cell behaviour and the initiation of many different metabolic, transcriptional or mechanical responses to environmental stimuli remain largely unexplained. To go beyond the status quo , the understanding of cell behaviours emerging from molecular genetics must be complemented with physical and physiological ones, focusing on the intracellular and extracellular conditions within and around cells. Here, we argue that such a combination of genetics, physics and physiology can be grounded on a bioelectrical conceptualization of cells. We motivate the reasoning behind such a proposal and describe examples where a bioelectrical view has been shown to, or can, provide predictive biological understanding. In addition, we discuss how this view opens up novel ways to control cell behaviours by electrical and electrochemical means, setting the stage for the emergence of bioelectrical engineering.


2019 ◽  
Vol 3 (4) ◽  
pp. 371-378
Author(s):  
Joshua M. Peters ◽  
Sydney L. Solomon ◽  
Christopher Y. Itoh ◽  
Bryan D. Bryson

Abstract Interactions between pathogens and their hosts can induce complex changes in both host and pathogen states to privilege pathogen survival or host clearance of the pathogen. To determine the consequences of specific host–pathogen interactions, a variety of techniques in microbiology, cell biology, and immunology are available to researchers. Systems biology that enables unbiased measurements of transcriptomes, proteomes, and other biomolecules has become increasingly common in the study of host–pathogen interactions. These approaches can be used to generate novel hypotheses or to characterize the effects of particular perturbations across an entire biomolecular network. With proper experimental design and complementary data analysis tools, high-throughput omics techniques can provide novel insights into the mechanisms that underlie processes from phagocytosis to pathogen immune evasion. Here, we provide an overview of the suite of biochemical approaches for high-throughput analyses of host–pathogen interactions, analytical frameworks for understanding the resulting datasets, and a vision for the future of this exciting field.


2019 ◽  
Vol 26 (6) ◽  
pp. R345-R368 ◽  
Author(s):  
Robert Clarke ◽  
John J Tyson ◽  
Ming Tan ◽  
William T Baumann ◽  
Lu Jin ◽  
...  

Drawing on concepts from experimental biology, computer science, informatics, mathematics and statistics, systems biologists integrate data across diverse platforms and scales of time and space to create computational and mathematical models of the integrative, holistic functions of living systems. Endocrine-related cancers are well suited to study from a systems perspective because of the signaling complexities arising from the roles of growth factors, hormones and their receptors as critical regulators of cancer cell biology and from the interactions among cancer cells, normal cells and signaling molecules in the tumor microenvironment. Moreover, growth factors, hormones and their receptors are often effective targets for therapeutic intervention, such as estrogen biosynthesis, estrogen receptors or HER2 in breast cancer and androgen receptors in prostate cancer. Given the complexity underlying the molecular control networks in these cancers, a simple, intuitive understanding of how endocrine-related cancers respond to therapeutic protocols has proved incomplete and unsatisfactory. Systems biology offers an alternative paradigm for understanding these cancers and their treatment. To correctly interpret the results of systems-based studies requires some knowledge of how in silico models are built, and how they are used to describe a system and to predict the effects of perturbations on system function. In this review, we provide a general perspective on the field of cancer systems biology, and we explore some of the advantages, limitations and pitfalls associated with using predictive multiscale modeling to study endocrine-related cancers.


Development ◽  
2009 ◽  
Vol 136 (21) ◽  
pp. 3525-3530 ◽  
Author(s):  
I. Roeder ◽  
F. Radtke

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