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Egenis · Research

Microbial rhodopsin research in translation:
Discovery, laboratory models and innovative applications (2009-2011)

Mathias Grote, Maureen O'Malley and Staffan Mueller-Wille

Start date

2009-01-01

Funded by

Co-funded by Egenis and the Max Planck Institute for the History of Science, Berlin

Background

Translation is often interpreted as the shift of a scientific object into the social realm of application. In this project, we investigated the dimensions and implications of translation processes, as phenomena move from ‘nature’ to the laboratory to useful invention. We suggest that translation will not be appropriately understood if it is understood serially, and if it is confined to the movement from scientific sphere to social use. Our focus was on two major periods of discovery and research development on microbial rhodopsins: in the 1970s and in the early 2000s. We examined the ways in which both types of microbial rhodopsin (bacteriorhodopsin and proteorhodopsin) were discovered, how they became laboratory exemplars, and what this exemplar status has meant for application and further research. These investigations go to the heart of scientific practice, the ways in which laboratory phenomena are constructed, and the role anticipated applications have in discovery and exemplar-forming activities. As well, we examined the relationships between two very different periods of the molecular life sciences: the first phase of publications on bacteriorhodopsin around 1970, and the postgenomic phase, in which the second microbial rhodopsin story is located.

1. Bacteriorhodopsin in science and technology

BackgroundAround 1970, scientists in San Francisco made a startling discovery: in the cellular membrane of the salt-loving microbe Halobacterium halobium, they found a protein similar to rhodopsin, the visual pigment in the retinae of vertebrate eyes. Bacteriorhodopsin, as the curious molecule was baptized, was shown to be also activated by light. This could serve the organism as a means of photosynthesis. Habitats of Halobacterium such as salterns thus appear crimson-colored due to the presence of it and related substances.

In the last four decades, bacteriorhodopsin has played a paradigmatic role for molecular life science fields such as bioenergetics or structural biology. The concept of integral membrane proteins transporting substances in and out of cells, for example, has been shaped by electron microscopic studies of the structure of this protein. Moreover, bacteriorhodopsin’s ability to pump protons across the cellular membrane has been employed in key experiments that support Peter Mitchell’s once controversial chemiosmotic hypothesis of energy generation.

Bacteriorhodopsin also moved quickly into a biotechnological focus. Using its ability to change colour upon illumination, 1970s researchers in the Soviet Union rapidly developed photographic films containing bacteriorhodopsin. These photoactive properties are still central to the use of microbial rhodopsins in today's science and technology. Bacteriorhodopsin is being developed as copy protection for ID-cards or paper money, while related proteins from algae are being used as ‘optogenetic tools’ for the control of animal behavior by means of light. In new and stunning experiments, neuroscientists have managed to manipulate the movements of laboratory mice. The neurons of these animals were genetically modified by channelrhodopsins that triggered action potentials in response to light.

Aims and objectivesBacteriorhodopsin illuminates a transdisciplinary research area that lies at the crossroads of physics, chemistry and biology. This research occurs in a period that has not hitherto received much attention by scholars of science. Based on published material, interviews with scientists and scrutiny of laboratory notebooks, we traced the passage of this material from a curiously coloured by-product of basic biochemical research towards a well-established object studied in many laboratories around the globe. This development maps onto a period in which the molecular life sciences have dramatically changed, due to the proliferation of recombinant DNA technologies and a massive rise of non-academic, commercial research. Moreover, both achieved and failed translations of rhodopsin research add a novel facet to the history of biotechnologies. All of these issues are centred around the more general question of how the objects of laboratory science come into existence, how they change in time and how they move out of the academic laboratory and back into society as products of technologies.

2. Proteorhodopsin research: discovery, experiment and application

BackgroundBacteriorhodopsin’s highly successful research programme has recently been supplemented and perhaps even overshadowed by a new discovery at the beginning of this century. In 2000, a novel rhodopsin was found in marine bacteria that had never been suspected to possess any light-sensing or light-energy production capabilities. Proteorhodopsin was the name given to this protein by its discoverers (led by Edward DeLong, now at MIT), because it was found originally in Proteobacteria. As with bacteriorhodopsin, this finding launched a major new research programme, in which molecular phylogeneticists, bioinformaticians, biophysicists, biochemists, and geneticists combined a wide array of techniques, independently and collaboratively.

Our project looked closely at the different modes of research organization in these two rhodopsin stories. Early research on bacteriorhodopsin took place at a time when the standardization of laboratory procedures by commercially available products and machines was still at a very low level and the work was carried out more or less exclusively by biochemists and biophysicists. This is in sharp contrast to the situation at the beginning of this decade, when laboratory work is dominated by standardized kits and automatic routines. Another aspect of science which dramatically changed during the period covered by the two microbial rhodopsin stories are the ways of representing the objects under study and their reliance on computational tools. Whereas bacteriorhodopsin research developed roughly in parallel to the digital revolution, proteorhodopsin was discovered at a time when high performance computing was already established as a tool to represent and analyse proteins in diverse ways.

Aims and objectivesAll of these factors and lines of investigation complicate the picture in a positive way, by providing rich and accessible comparative material that will enable deep insight into scientific practice. The second, comparative part of this project was directed towards a closer examination of the relationship between theory- or hypothesis-driven and data-driven science. Metagenomics, the approach that allowed the proteorhodopsin discovery to be made, is often characterized as ‘mere‘ or ‘mindless’ information gathering that is inferior to hypothesis-driven research. This is an opinion that has been frequently aired in relation to genomics of every kind, and to large protein structure projects as well. We used what we learnt in the first phase of comparative study to examine the characteristics and impact of exploratory research on more traditionally conceived scientific practice, and what this means in terms of translation. Our final comparison was of the ways in which proteorhodopsin and bacteriorhodopsin efforts are being turned into applications. We were particularly interested in investigating the differences between the 1970s and 2000s regarding the translation of research into commercially or socially useful knowledge.

Publications

Grote M, O'Malley M.A., Enlightening the life sciences: The history of halobacterial and microbial rhodopsin research. FEMS Microbiology Review, 35 (6): 1082-1099, November 2011.

Grote, M., and O'Malley, M.A., History of science is good for you. Nature Reviews Microbiology, 8, 2010, p.752.

Grote, M (2010). Surfaces of action: Cells and membranes in electrochemistry and the life sciences. Studies in History and Philosophy of Biological and Biomedical Sciences (special issue on the history and philosophy of cell research), 41 (3): 183-193.

O'Malley, M.A. (2008). Exploratory experimentation and scientific practice: Metagenomics and the proteorhodopsin case. History and Philosophy of the Life Sciences, 29 (3): 335-358.Workshop: Membranes, Surfaces, Boundaries: Interstices in the History of Science, Technology and Culture, October 2010, MPIWG Berlin.