Class Note for BIOC 462A at UA
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Date Created: 02/06/15
Rams llEFrro erlows HovKleMEDKAl lenrumNsmmrzuzx umvzmv mque and founded a company Form which makes MRI machines today The machines use a VeIsion of Lauteibuis gtadient meth ods hoWeVeI Damadian believes that he should have been included in the Nobel await last week his company took om full page ads in The Washinglon Post and The New York Times objecting to the shameful Wtong that must be lighted and mging lead eIS to suppolt his cause Damadian pub lished some eatly papels omlining the con oept says Geofge Radda an MRI expeit at the Univetsity of Oxfotd and foImeI chief of the UKs Medical Reseaxch Council Bm he adds Damadians idea fol detecting specific signals om canoetous tissue did not lead to todays MRI Damadian did not Iespond to The 2003 Nobel Ptizte in chemisuy honoIs Pete Agle and Roderick MacKinnon fol lheit pioneeting WoIk on ploteins that con uol which molecules pass into and out of cells These gatekeepets ate the basis of many vital functions including the geneta tion of nere impulses and the ability to eg ulate the conoenuation of mine Agle 54 of Johns Hopkins school of Medicine in Baltimote Maxyland claims half of the pIize fol his discovery of watef chan nels These plotein poles shuttle watef into and om of oells much fastet than it could diffuse though hell fatty outeI membtanes speed is particulaxly clitical in the kidney which Ieclaims watef om the mine to pIevent dehydiation You d pee out 50 gallons ofvvatet a day if these channels didn t fillet the Wale back into the body says Robett suoud a biophysicist at the Univetsity of Califomia San Flancisco Agte s blight futute in chem isuy Wasn t always appalent He got a D in the subject in high school despite having both a fa lhet who was a chemisuy pIofes so and he leadin admits a perfectly good chemisuy teachet 1 was kind ofa negligent high school student mole intetested in mak ing mischief he says Agtes big bleaklhlough had an element of setendipity A Iheumatologist by twining he was intetested in identifying Rh antigens sutfaoe ploteins on ed blood cells that give blood types theii positive of negative www3ciencemagorg SCIENCE VOL302 Science s quuests fol comment The bittemess of the eaIly Iiwllies may have delayed the awaxding of the pIiZle says Radda Except fol the contIoveIsy it could have been given 10 yeats ago he says The contnbutions of Lauterul and Mansfield Ilse to the top Thete is no question that these axe the light two people to Ieceive the ptizehe says Lantetbul desetves a lot of ctedit not only fol the inwntion of the idea bm also fol pioselytizing says Waldo Hinshaw who was a postdoctotal fellow in the lab of Ray mond AndIeW in the eatly 1970s and helped develop some of the imaging techniques used in today s MRI machines Rally on Hinshaw notes people doubted that magnets Gateways Into Cells Usher in Nobels designation But his scIeens Iepeatedly net ted a zskilodalton plotein that seemed to have nothing to do with Rh It was ptewlent not just in ed blood cells but also in the tubules of the kidney Agle ctedits his foImeI mentoI at the Univetsity of Notth Caxolina Chapel Hill John PaIkeI fol suggesting that the plotein CHEMISTRY A t Crystallixed honors PelerAgIe left and Roderick MacKinnon exposed discriminan39ng channels mat allow molecules m pass in and out of cells could be a watei channel As eatly as the mid1800s scientists had ploposed that oells might need such channels to maintain osmotic balance but they d neVeI been found and some biophysicists axgued that diffusion alone could do the tfick The mat tel was settled when Agte s team put the plotein subsequently tetmed aquapotin into flog eggs and pm the eggs in a water 17 OCTOBER 2003 NEWS Focus big enough and poWeIful enough to ploduoe highly detailed images of the human body could be built But he adds Lautetbut went axound to eVerone he thought might be intetested and said Take it seriously He even showed up at my apaxtment in Not tingham one evening to convince me that it was wonhwhile Even befoIe the pIiZle Lauterul says the WOIk has paid off in a deeply petsonal way quotThe most satisfying thing petsonally is when a physician looks at an MRI and says No pIoblem lhetel which I have ex petienoed and Ielatives of mine have expell enoed he says And lhat can be almost as tlnilling as witmingaNobel Ptize GRHCHEN VOGEL solution Science 17 ApIil 1992 p 385 The cells ballooned up and exploded befote hell eyes as watei gushed in Reseaxchets have since identified 11 hu man aquapoiinsAome of which play a ole in diseasesand many mole in bactetia and plants 1 think Agies discovety is Ieally one of the big bleakthioughs in physiology says Robett Schliel a nephlologist at the Uni Vetsity of Colotado Health Scienoes Genie in DenveI It was followed by a second big peak in the mountain chain of WoIk that led to Agte s Nobel says Maxk Kneppel of the National Heart Lung and Blood Institme in Bethesda Matyland stmctutal studies that Ievealed how the channel WoIks This is pIobably the Ieason it s the chemistty pfize says KneppeI Ialhet than a physiologyNobel Each aquapotin channel can pass about a billion watei mole cules pet second Yet the channels exclude othet moleculesimost notably plotons in the foIm of H30 ions In Iecent yeats Agte s gloup has Ievealed the sectet to this IemaIkable selectivity AtomicIesolution images of an aquapotin showed that each chan nel accommodates about 10 watef molecules at a time lined up sin gle file The plotein s elecuic field foIces the positively chafged hy diogens on each watei molecule to point away om the oentet of the channel so that hydogens on half of the WateIs point tovvmd the outside of the cell Wheteas those on the olhethalfpoint into the cell This otientation both Iepels plotons rom the ends of the channel and pIeVents them rom ctossing though by hopping om one Wale molecule to the next Choosy channels ale also the focus of MacKinnon s WoIk In the eatly 1990s while 383 News Focus at Harvard Medical School MacKinnon de cided that to really understand the channels he was studying he needed to see them That meant learning to do xray crystallographyi a monumental undertaking tantamount to changing careers A lot of us questioned it says a postdoc in MacKinnon s lab during that em Kenton Swartz now at the National Institute of Neurological Disorders and Stroke in Bahesda Maryland Getting mem brane proteins to crystallize is notoriously di icult and ion channels are even more un wieldy than most It seemed like a piein thesky idea even to me MacKinnon con cedes But it paid o In 1998 MacKinnon sent ajolt through the field with the first highresolution pic ture of an ion channel derived from xray crystallography Science 3 April 1998 pp 69 and 106 Based on the crystal structure his team later presented an elegant model ofhow ionFin this case potassiumionk pass through the core of the channel and explained the channel s ability to let potas sium ions through while excluding smaller sodiumions Just as a rock star moves through a crowd with a ring of bodyguards clinging to his person a sodium or potassium ion moves through a solution with an entourage of water molecules Passing through the potassium channels selectivity filter how ever requires leaving the escorts behind The filter makes this easy for potassium ions by providing four conveniently located carbonyl groups Potassium forms bonds with these just as easily as it does with wa ter and so it slips through the filter leaving its waters behind Sodium however is smaller As a result it can only bind two of the carbonyl groups at a time This doesn t provide the energetic incentive needed to lure sodium ions away from their waters thus the ions retain their escorts and stay outside the filter Although many in the field had predicted MacKinnon would one day take home a No bel for this work most envisioned him get ting a slice of the physiology prize I think the choice of chemistry is actually very 384 clever says Gary Yellen a biophysicist at Harvard Medical School in Boston Al though the question of how ion channels achieve their selectivity is critically impor tant for biology Yellen says the answer was ultimately a matter of chemistry Three theorists have gotten a warm recep tion for their work on the very cold Vitaly Ginzburg Alexei Abrikosov and Anthony Leggett have been awarded this year s Nobel Prize in physics and will split the 10 million kronor 13 million award Ginzburg of the P N Lebedev Physical Institute in Moscow and Abrikosov currently at Argonne National Laboratory in Argonne Illinois were honored for their work on superconductors materials that lose all elec trical resistance at very low tenperatures In 1950 Ginzburg and a colleague Lev Lan dau formulated a theory that describes how superconductors behave in a magnetic field Prizewinning proteins This year39s chemistry Nobel recognizes work on potassium channels near left and aquaporins More recently MacKinnon now at Rock efeller University in New York City stirred up the field with the rst portmit of a voltage gated ion channel These channels reload nelrons after they ve fired an inpulse Based on the channels structure MacKinnon s team presented a model of its mechanism that ew in the face of the View widely held by re searchers in the eld many of whom refused to accept it Science 27 June p 2020 But even the critics acknowledge the research as a tremendous accomplishment and say it has energized the field He certainly deserves this says Clay Armstrong of the University of Pennsylvania in Philadelphia He s packed two orthree careers into 10 years Guzc MILLER Cool Theories Garner Super Kudos The GinzburgLandau theory implied that superconductors can respond in two di er ent ways when exposed to everstronger magnaic fields Type I superconductors are completely impermeable to magnetism the field lines can t pass through the superconduct ing material at all If the magnetic field gets too strong for the material to resist the superconductivity disappears Type II superconductors which include all of the famous hightemperature ones allow field lines to penetrate under some conditions Abrikosov built upon the Ginzburg Landau theory to characterize the behavior of type II superconductors he predicted for example that penetrating field lines would create a regular lat tice pattern in the super conductor a phenomenon observed directly in 1967 PHYSICS Superheroes Laureate Anthony Leggett left plunged into liquid heliumVitaly Ginzburg cenr ter and Alexei Abrikosov braved the resistance free currents of type II superconductors nrolr rovroaorroM LEFH39ORlCHl KXKEEELLERUvaERSNYJHENOBELMUSEUMalulemNDUNNERXWOEllllNOlAleDERZEMUANKHENmAPSTEPHEN i ARRERAAP 17 OCTOBER 2003 VOL 302 SCIENCE www5ciencemagorg
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