53945. doi:10.1016/0006-3002(58)90516-X. PMID 13560404.External linksThe Register of Harvey Itano Papers 1946 - 2000 - UC San DiegoKey Participants: Harvey Itano - It's in the Blood! A Documentary History of Linus Pauling, Hemoglobin, and Sickle Cell Anemia Seymour Jonathan Singer (S.J.Singer) , numerosos trabalhos de pesquisa nesta area, S. Jonathan Singer e tambem membro da Academia Nacional de Ciencias e da Academia Americana de Artes e Ciencias.Seymour Jonathan Singer is a cell biologist and professor at the University of California, San Diego. He worked as a postdoctoral fellow in the lab of Linus Pauling at Caltech, where he co-discovered the basis of abnormal hemoglobin in sickle-cell anemia, reported in the famous paper "Sickle Cell Anemia, a Molecular Disease". In 1951, he became an assistant professor at Yale, where he developed the ferritin-antibody, which was the first electron-dense reagent used for cell staining in electron microscopy imaging. In 1961 he joined the faculty at UCSD. He then began to work on membrane proteins and aided in the development of the "Fluid Mosaic Model" of the cell membrane. He later studied the cytoskeleton. In 2001, he published a book, "The Splendid Feast of Reason", regarding rationalism and the philosophy of science. Figure 1: Original figure from Singer (1992) illustrating the Davson-Danielli-Robertson model of the plasma membrane. Notice that the lipid bilayer is isolated from the surrounding aqueous environment by two layers of unfolded membrane protein (p). Each membrane forming lipid is composed of a polar head group (h) and fatty acyl tail (f). Text added. Figure 3: Original figure from Singer and Nicolson (1972) depicting membrane cross section with integral proteins in the phospholipid bilayer. The ionic and polar portions of the proteins, as indicated by the +/- signs, contact the aqueous solutions (cytoplasm and/or interstitial fluid) surrounding the lipid bilayer. The membrane spanning or inserted region of the protein is non-polar/hydrophobic and therefore lacks charge as indicated by the absence of +/- symbols.Although the bilayer nature of the cell membrane was described in the mid-1920's, it was not until 1972 that the currently accepted model of the plasma membrane, the fluid mosaic model, was formally outlined by S. J. Singer and Garth L. Nicolson in the journal Science. Singers work on membrane structure originated in the 1950s when he, along with other protein chemists, demonstrated that many water-soluble proteins like those found in cytoplasm could unexpectedly dissolve in nonaqueous, non-polar solvents. Furthermore, the shape a protein assumed differed in hydrophobic and hydrophilic environments (Singer, 1992). From an historical perspective these results are significant because they led Singer to wonder about the structure of the proteins revealed to be closely associated with lipid-rich, and therefore nonaqueous, cell membranes in the 1930s (Eichman, 2007). As he later wrote, Although we had not experimented with membrane proteins and knew very little about membranes at the time, as almost an aside we speculated [in a 1962 publication] that because the cellular environment of many proteins contains high concentrations of lipid components in a wide variety of cellular membranes, the gross conformations of these proteins in situ may be