Conceptual Challenges in the Theoretical Foundations of Systems Biology

Bertolaso, Marta; Ratti, Emanuele

doi:10.1007/978-1-4939-7456-6_1

Cited by 10 publications

(11 citation statements)

References 42 publications

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“…This way of conceptualizing stem cell microenvironment seems to be inadequate and potentially misleading, because it gives the impression that microenvironment constituents modulate stem cells fate separately and individually. In fact, the causal relationship between stem cells and their microenvironment can better be grasped by adopting a relational and dynamical ontology that considers biological levels and processes as mutually related, leading to macroscopic behaviors that are emergent and time dependent (Bertolaso 2016).…”

Section: Stem Cell Microenvironment As a Network Of Asymmetric Mutual...mentioning

confidence: 99%

“…In such a framework, there is neither an upward (from stem cells to tissue microenvironment) nor a downward (from tissue microenvironment to stem cells) causation, but rather a bidirectional model of causation in which stem cells constrain the behavior (i.e., the mechanisms) of the other components of the niche and vice versa (see Bertolaso 2016;Bertolaso and Velázquez 2022). Here, two clarifications are necessary.…”

Section: Stem Cell Microenvironment As a Network Of Asymmetric Mutual...mentioning

confidence: 99%

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Stem Cells and the Microenvironment: Reciprocity with Asymmetry in Regenerative Medicine

Militello

Bertolaso

2022

Acta Biotheor

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Much of the current research in regenerative medicine concentrates on stem-cell therapy that exploits the regenerative capacities of stem cells when injected into different types of human tissues. Although new therapeutic paths have been opened up by induced pluripotent cells and human mesenchymal cells, the rate of success is still low and mainly due to the difficulties of managing cell proliferation and differentiation, giving rise to non-controlled stem cell differentiation that ultimately leads to cancer. Despite being still far from becoming a reality, these studies highlight the role of physical and biological constraints (e.g., cues and morphogenetic fields) placed by tissue microenvironment on stem cell fate. This asks for a clarification of the coupling of stem cells and microenvironmental factors in regenerative medicine. We argue that extracellular matrix and stem cells have a causal reciprocal and asymmetric relationship in that the 3D organization and composition of the extracellular matrix establish a spatial, temporal, and mechanical control over the fate of stem cells, which enable them to interact and control (as well as be controlled by) the cellular components and soluble factors of microenvironment. Such an account clarifies the notions of stemness and stem cell regeneration consistently with that of microenvironment.

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Section: Stem Cell Microenvironment As a Network Of Asymmetric Mutual...mentioning

confidence: 99%

Section: Stem Cell Microenvironment As a Network Of Asymmetric Mutual...mentioning

confidence: 99%

Stem Cells and the Microenvironment: Reciprocity with Asymmetry in Regenerative Medicine

Militello

Bertolaso

2022

Acta Biotheor

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“…However, it is not exactly clear how this might be possible – if entities at lower levels have certain characteristics that make them behave in certain ways, how do we make sense of system constraints? By drawing on previous work (Bertolaso and Ratti, 2018), we propose to use a relational ontology to ground both the conceptual and explanatory aspects of this issue.…”

Section: Relational Ontology For Biological Propertiesmentioning

confidence: 99%

“…Genes can be specified in terms of intrinsic properties (i.e., the gene x is a specific sequence of nucleotides), while in other contexts such as in networks biology a specific gene is defined as a node within a network of interactions (Barabasi and Oltvai, 2004) defined by a set of descriptors related to its connectivity features (e.g., degree, clustering coefficient, etc.). However, as Bertolaso and Ratti (2018) say “the fact that a gene has a specific sequence, and the fact that this sequence has a certain causal role (i.e., being transcribed as a blueprint for a specific protein) strictly depend on the context where the gene happens to be. Therefore, even properties that seem prominently internal are somehow relational, i.e., they depend on the context.”…”

Section: Relational Ontology For Biological Propertiesmentioning

confidence: 99%

Co-emergence and Collapse: The Mesoscopic Approach for Conceptualizing and Investigating the Functional Integration of Organisms

et al. 2019

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The fall of reductionist approaches to explanation leaves biology with an unescapable challenge: how to decipher complex systems. This entails a number of very critical questions, the most basic ones being: “What do we mean by ‘complex’?” and “What is the system we should look for?” In complex systems, constraints belong to a higher level that the molecular one and their effect reduces and constrains the manifold of the accessible internal states of the system itself. Function is related but not deterministically imposed by the underlying structure. It is quite unlikely that such kind of complexity could be grasped by current approaches focusing on a single organization scale. The natural co-emergence of systems, parts and properties can be adopted as a hypothesis-free conceptual framework to understand functional integration of organisms, including their hierarchical or multilevel patterns, and including the way scientific practice proceeds in approaching such complexity. External, “driving” factors – order parameters and control parameters provided by the surrounding microenvironment – are always required to “push” the components’ fate into well-defined developmental directions. In the negative, we see that in pathological processes such as cancer, organizational fluidity, collapse of levels and dynamic heterogeneity make it hard to even find a level of observation for a stable explanandum to persist in scientific practice. Parts and the system both lose their properties once the system is destabilized. The mesoscopic approach is our proposal to conceptualizing, investigating and explaining in biology. “Mesoscopic way of thinking” is increasingly popular in the epistemology of biology and corresponds to looking for an explanation (and possibly a prediction) where “non-trivial determinism is maximal”: the “most microscopic” level of organization is not necessarily the place where “the most relevant facts do happen.” A fundamental re-thinking of the concept of causality is also due for order parameters to be carefully and correctly identified. In the biological realm, entities have relational properties only, as they depend ontologically on the context they happen to be in. The basic idea of a relational ontology is that, in our inventory of the world, relations are somehow prior to the relata (i.e., entities).

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“… 6 6 It is important to warn the reader about the specificity of the methodology that we are following, which is related to relational ontology (Bertolaso, 2018; Bertolaso & Ratti, 2018). There is also a history of failures associated with the transposition of paradigms which are valid for the natural world into policies that are applicable on a societal scale, e.g.…”

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confidence: 99%

Specifically human: Human work and care in the age of machines

Bertolaso¹,

Rocchi

2020

Business Ethics Env & Resp

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This paper aims to show how the frequently asked question about the future of work, that is, whether human beings are going to be replaced by machines and robots, arose, and why the way such question is posed is inadequate to account for the human and social value of care professions. We discuss how the dimensions entailed in care professions are specifically human and argue that any kind of human work actually reflects them (and will reflect them in the future), irrespective of the impact of technological changes. The present argument also aims to unveil the extent of the effects of the postmodern epistemological crisis regarding the concept of work, to reformulate the question about the future of human work, and to offer a characterization of care as a specific component of human work in the age of machines.

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Conceptual Challenges in the Theoretical Foundations of Systems Biology

Cited by 10 publications

References 42 publications

Stem Cells and the Microenvironment: Reciprocity with Asymmetry in Regenerative Medicine

Stem Cells and the Microenvironment: Reciprocity with Asymmetry in Regenerative Medicine

Co-emergence and Collapse: The Mesoscopic Approach for Conceptualizing and Investigating the Functional Integration of Organisms

Specifically human: Human work and care in the age of machines

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