Abstract

For all we know (and will never know) about the workings of the human brain, in both healthy and diseased states, it is comforting to consider that we at least have a fundamental grasp on how neurons speak to each other using chemical messengers secreted in tiny vesicles from one cell to its neighbour. There is an elegant choreography and a mind-boggling speed to these reactions; an apparent simplicity masking the fiendish complexity. Fitting, then, that two of the principal architects of this understanding, Richard Scheller and Thomas Sudhof, are recipients of this year’s Albert Lasker Basic Medical Research Award. Sudhof and Scheller receive their Lasker Award (dubbed America’s Nobel Prize in some quarters) for elucidating the precise protein machinery responsible for cellular communications at the molecular level. Without it, we would have much less of an idea how brain dysfunctions occur, and far fewer protein targets to try to fi x diseases like Alzheimer’s and schizophrenia with drugs. “These discoveries were before their time”, says Rob Malenka, a molecular neurobiologist and psychiatrist based at Stanford University School of Medicine, CA, USA. “Without their work we would be 10–20 years behind in our understanding of the molecular basis of synaptic function.” The basics of chemical transmission from the ends of nerves, synapses, by vesicles prompted by a calcium influx had been sketched out from the 1950s. Decades later, Sudhof and Scheller entered the research landscape knowing that deciphering the exact proteins behind vesicle formation and fusion with the synaptic membrane was a fundamental biological question. Crucially, Malenka says, from the mid-1980s they appreciated it was a tractable problem, solvable using the emerging techniques of the time. They are both worthy winners, he adds, because their techniques contrasted and complimented each other well, confi rming the other’s fi ndings. For example, while at Stanford University School of Medicine, Scheller isolated the protein VAMP 1 from the electric organ of a marine ray; a year later Sudhof, then working from the University of Texas Southwestern Medical Center, TX, USA, found the same molecule in a rat’s brain and

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