Grounding knowledge and normative valuation in agent-based action and scientific commitment

Philosophical investigation in synthetic biology has focused on the knowledge-seeking questions pursued, the kind of engineering techniques used, and on the ethical impact of the products produced. However, little work has been done to investigate the processes by which these epistemological, metaphysical, and ethical forms of inquiry arise in the course of synthetic biology research. An attempt at this work relying on a particular area of synthetic biology will be the aim of this chapter. I focus on the reengineering of metabolic pathways through the manipulation and construction of small DNA-based devices and systems synthetic biology. Rather than focusing on the engineered products or ethical principles that result, I will investigate the processes by which these arise. As such, the attention will be directed to the activities of practitioners, their manipulation of tools, and the use they make of techniques to construct new metabolic devices. Using a science-in-practice approach, I investigate problems at the intersection of science, philosophy of science, and sociology of science. I consider how practitioners within this area of synthetic biology reconfigure biological understanding and ethical categories through active modelling and manipulation of known functional parts, biological pathways for use in the design of microbial machines to solve problems in medicine, technology, and the environment. We might describe this kind of problem-solving as relying on what Helen Longino referred to as “social cognition” or the type of scientific work done within what Hasok Chang calls “systems of practice”. My aim in this chapter will be to investigate the relationship that holds between systems of practice within metabolic engineering research and social cognition. I will attempt to show how knowledge and normative valuation are generated from this particular network of practitioners. In doing so, I suggest that the social nature of scientific inquiry is ineliminable to both knowledge acquisition and ethical evaluations

Varieties of living things: Life at the intersection of lineage and metabolism

publication-status: Publishedtypes: Articl

Extracellular Forms of Aβ and Tau from iPSC Models of Alzheimer’s Disease Disrupt Synaptic Plasticity

The early stages of Alzheimer’s disease are associated with synaptic dysfunction prior to overt loss of neurons. To identify extracellular molecules that impair synaptic plasticity in the brain, we studied the secretomes of human iPSC-derived neuronal models of Alzheimer’s disease. When introduced into the rat brain, secretomes from human neurons with either a presenilin-1 mutation, amyloid precursor protein duplication, or trisomy of chromosome 21 all strongly inhibit hippocampal long-term potentiation. Synaptic dysfunction caused by presenilin-1 mutant and amyloid precusor protein duplication secretomes is mediated by Aβ peptides, whereas trisomy of chromosome 21 (trisomy 21) neuronal secretomes induce dysfunction through extracellular tau. In all cases, synaptotoxicity is relieved by antibody blockade of cellular prion protein. These data indicate that human models of Alzheimer’s disease generate distinct proteins that converge at the level of cellular prion protein to induce synaptic dysfunction in vivo

Production and use of recombinant Aβ for aggregation studies

The amyloid β-protein (Aβ) is believed to play a central role in Alzheimer’s disease (AD) pathogenesis and there is great interest in understanding the process of Aβ aggregation, its underlying mechanism and the species generated during aggregation and their biological activity. Although Aβ has been studied for more than 30 years, analysis of its aggregation has been hampered by structural and chemical impurities. Here we provide a detailed protocol for the expression and purification of chemically and structurally homogeneous Aβ monomer. We also describe a method to produce covalent Aβ dimers linked by phenolic coupling of tyrosine residues

Copper Redox Cycling Inhibits A beta Fibre Formation and Promotes Fibre Fragmentation, while Generating a Dityrosine A beta Dimer

We are thankful for the support of the China Scholarship Council and the BBSRC; project grant code BB/M023877/1