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STEROID RECEPTOR MODEL. “Comparison of the sequences revealed a conserved evolutionary template, and it also permitted the delineation of the structural and functional features that foreshadowed the emergence of a nuclear receptor superfamily.” https://lnkd.in/dXjCCgQ View in LinkedIn

UNPREDICTABLE INNOVATION. "And contrary to those who would have you believe that the golden era of innovation is behind us, the rate of this progress shows no signs of slowing. It just doesn’t always follow the paths that the experts predict." http://www.slate.com/articles/technology/superman/2013/03/superman_2_0_how_human_enhancement_technologies_are_giving_us_all_superpowers.html View in LinkedIn

FIRST BIG BREAKTHROUGH. “The isolation of the first complete steroid receptor cDNAs, the glucocorticoid and estrogen receptors, was transformative.” https://lnkd.in/dXjCCgQ View in LinkedIn

NO FANTASY WORLD. "The Age of Enhancement. Technology is starting to give us superpowers once reserved for comic-book heroes." http://www.slate.com/articles/technology/superman/2013/03/superman_2_0_how_human_enhancement_technologies_are_giving_us_all_superpowers.html View in LinkedIn

METHODOLOGICAL LIMITATIONS. “The idea of a “Nuclear Receptor” that could directly translate simple chemical changes into distinct physiologic effects persisted for several decades, but the fundamental nature of this receptor, its means for recognizing specific chemical ligands, its mode of interaction with the genome, and its mechanism for control of gene transcription were all beyond the limits of classic biochemical analysis.” https://lnkd.in/dXjCCgQ View in LinkedIn

WHITE PAPER. "Enhancement technologies could change how people work. Work will evolve over the next decade, with enhancement technologies potentially making a significant contribution. Widespread use of enhancements might influence an individual’s ability to learn or perform tasks and perhaps even to enter a profession." https://lnkd.in/d8guUtt View in LinkedIn

CASCADE REACTIONS. “Steroid and thyroid hormones, along with vitamins A and D, were elucidated based on their endocrine origin and the physiologic processes that they regulate. Each of these small molecules is chemically distinct, and although there was initially no presumption that they might have a shared signaling mechanism, initial biochemical experiments revealed the presence of an intracellular receptor that, upon ligand addition, activated transcription of tissue-specific sets of target genes.” https://lnkd.in/dXjCCgQ View in LinkedIn

THEN CAME THE ORPHANS. “This discovery sparked identification of numerous genes encoding related proteins, termed orphan receptors. Characterization of these orphan receptors and, in particular, of the retinoid X receptor (RXR) positioned nuclear receptors at the epicenter of the “Big Bang” of molecular endocrinology.” https://lnkd.in/dXjCCgQ View in LinkedIn

STARTING WITH GENES. “Isolation of genes encoding the receptors for steroids, retinoids, vitamin D, and thyroid hormone and their structural and functional analysis revealed an evolutionarily conserved template for nuclear hormone receptors.” https://lnkd.in/dXjCCgQ View in LinkedIn

FRAGMENT FROM NATURE this weekend is a historical vignette on the discovery of nuclear receptors in cells, based on a lovely 2014 review by Ronald Evans and David Mangelsdorf. The gene isolation of nuclear receptors led to the discovery of receptors without known function, so-called “orphan receptors” which eventually were assigned to functional pathways. Importantly, these orphan receptors belonged to large conserved superfamilies. This was effectively the start of molecular endocrinology, a far-reaching discipline that had a big impact on medicine. View in LinkedIn