Browsing by Subject "Developmental biology"
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Item Generalizations in Practice: Investigating Generality and Specificity in Developmental Biology(2023) Yoshida, YoshinariAlthough there is a consensus that pursuits of general knowledge are crucial in almost all fields of science, the majority of philosophical analyses of generalizations have focused narrowly on universal generalizations or laws of nature and what role generalizations play in scientific explanations. This narrow focus has limited the scope of philosophical discussions about scientific generalizations. This dissertation proposes and exemplifies a broader inquiry into scientific generalizations that is motivated by the question: how do scientists pursue, formulate, reason about, utilize, and communicate generalizations? In other words, how are generalizations practiced in science? To address this broad set of questions, I focus on a particular field—developmental biology—and examine investigative and representational practices surrounding generalizations. Like many other fields, developmental biology seeks both widely shared regularities and the details of causal processes peculiar to specific systems. My analyses show how this dual interest in generality and specific details is interconnected and mutually contribute to each other. This dissertation is organized as follows. Chapter 1 provides a brief overview of how philosophers have discussed generalizations. I point out that the interests in laws and explanation have dominated the past discussions. In contrast, my approach focuses on investigative and representational practices of generalization, which have received very little philosophical attention. Chapter 2 analyzes two approaches to generalizations in developmental biology: mechanisms and principles. These are distinguished based on the relevance of abstraction. I show that the two approaches are associated with different investigative practices. This analysis illustrates what forms of non-universal generalizations developmental biologists seek and formulate, which serves as a basis for discussions in the following chapters. Chapter 3 explores generalizations from the perspective of modeling desiderata. I offer a characterization of what I call multiple-models juxtaposition (MMJ), a strategy for managing a trade-off between generality and detail in scientific models. MMJ displays models of distinct processes together and fulfills different desiderata both in the individual models and by a comparison of those models. I also clarify the distinction between MMJ and multiple-models idealization (MMI), which also uses multiple models to manage trade-offs among desiderata. Chapter 4 focuses on the use of model systems. Biologists often study particular biological systems as models of a phenomenon of interest, even if they know that the phenomenon is produced by diverse mechanisms and hence none of those systems alone can sufficiently represent it. I argue that even if generalizability of results from a single model system is significantly limited, generalizations concerning specific aspects of mechanisms often hold across certain ranges of biological systems. This enables multiple model systems to jointly represent such a phenomenon. Chapter 5 considers the question “how and why do scientists generalize?” by challenging three influential assumptions: (1) generalizations are expressed linguistically; (2) scientists generalize by formulating a single representation with wide applicability; and (3) generalizations are valuable because they enable scientific explanations. My analysis of a concrete example illustrates roles that visual representations play in generalizations. It also shows that formulating a single, unified representation is not the only way to generalize; scientists often generalize by configuring multiple representations. Finally, I argue that generalizations serve to facilitate cross-fertilization among studies of different target systems, which complements the explanation-centered view.Item Rab GTPase mediated regulation of the autophagic pathway and mTOR signaling in the larval fat body of Drosophila melanogaster(2016-07) Ayala-Navarro, Carlos IAutophagy is a conserved lysosomal dependent pathway employed by cells during stress conditions as an alternative source of nutrients to maintain cellular homeostasis and promote survival. The pathway is negatively regulated by the mechanistic target of rapamycin (mTOR) and induced by depletion of nutrients. Over the last decade input in the form of vesicular traffic from an array of cellular organelles (e.g. Golgi, ER, endocytic pathway and mitochondria) has been shown to be required for the delivery of proteins, enzymes and lipids during progression of the autophagic pathway. However, how these organelles switch from their constitutive roles to supply the autophagic pathway with proteins and lipids upon induction is not fully understood. In addition the extent to which these cellular organelles modulate autophagosomal growth and mTOR-Insulin signaling remains incompletely understood. The main goal of this thesis was to uncover novel traffic regulators of the Rab GTPase family required for starvation-induced autophagy in Drosophila fat body cells and evaluate their role in mTOR signaling regulation. To this end we carried a reverse screen using RNAi to knockdown 30 of the 33 Drosophila Rab GTPases. We show Rab 2, 7 and 14 GTPases are required for the induction and growth of autophagosomes and autolysosomal function. Rab5 is required for autophagic vesicle induction and growth, endocytosis and lysosomal maturation. Lastly, that Rab6 is required for the sorting of lysosomal hydrolases, autolysosome turnover and the regulation of mTOR signaling via regulation of the insulin receptor localization in fat body cells. Altogether we uncovered novel regulators in the vesicular traffic regulator Rab GTPase family required for autophagy and mTOR-Insulin signaling regulation in Drosophila.