Pasteur Institute, Paris, France
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Jean-Pierre Changeux |
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Jean-Pierre G. Changeux is Professor at the Pasteur Institute and at the Collège de France, Paris. He received his Ph.D. in 1964 from Paris University and from 1965-67 completed postdoctoral studies at University of California, Berkeley and Columbia University College of Physicians & Surgeons, New-York. He is member of the National Academy of Sciences, USA and of several foreign academies, and received in particular the Richard Lounsbery prize, the Wolf prize, the Balzan prize, the American Philosophical Society's Karl Spencer Lashley award in neuroscience and the Lewis Thomas Prize for Writing about Science.
Changeux's work has combined meticulous biochemical and functional molecular dissection and theoretical modeling to establish several elementary mechanisms of intracellular and intercellular regulation. As a graduate student, Changeux established the molecular mechanisms underlying bacterial enzyme regulation by selected metabolic ligands and suggested a model for enzymes in which regulatory signals of enzymatic activity were held to act at "allosteric" sites distinct from the sites at which the substrates of the enzyme would bind. His subsequent career strategically and comprehensively validated his pioneering insight, and has lead to important discoveries first with the identification of the acetylcholine receptor and of its allosteric transitions, second into a variety of peripheral central nervous system functions, in part regulated by cholinergic circuits.
Changeux and his team's empirical and theoretical works in the 70's have included the analysis of synapse formation and the extension of a mechanism of "evolution by variation-selection" to the epigenesis of developing neuronal networks by selective stabilization of synapses. In the 90's Changeux and his collaborators have extended their work to nicotinic receptors in the brain, and have demonstrated in mouse models the selective contribution of specific brain nicotinic receptor subunits to nicotine addiction and to executive functions, learning processes, self administration of nicotine, nicotine antinociception and neuroprotection during aging. They were the first to develop the so-called concept of the "sickness of the receptor", which has today achieved fundamental significance. Other research teams have taken up this concept and been able to reveal that some epilepsy is associated with the mutations which alter the allosteric properties of the receptor and that Attention deficit hyperactivity disorders, sudden infant death, and Alzheimer disease are also connected to a deficit of nicotinic receptors.
Last, Changeux and his colleagues have proposed a neural model for access to consciousness, thereby establishing plausible links between the molecular and cognitive levels with the general aim to account for the molecular and neuronal bases of behavior. |
