Dieter Oesterhelt (1940-2022).

Pioneer of membrane protein research.

Tatsushi Igaki: Flying up the research summits.

Igaki explores how cell-cell communication directs tissue and tumor development.

Membrane protein serendipity.

My scientific career has taken me from chemistry, via theoretical physics and bioinformatics, to molecular biology and even structural biology. Along the way, serendipity led me to work on problems such as the identification of signal peptides that direct protein trafficking, membrane protein biogenesis, and cotranslational protein folding. I've had some great collaborations that came about because of a stray conversation or from following up on an interesting paper. And I've had the good fortune to be asked to sit on the Nobel Committee for Chemistry, where I am constantly reminded of the amazing pace and often intricate history of scientific discovery. Could I have planned this? No way! I just went with the flow ….

Hemochromatosis: Niche Construction and the Genetic Domino Effect in the European Neolithic.

Hereditary hemochromatosis is caused by a potentially lethal recessive gene (HFE, C282Y allele) that increases iron absorption and reaches polymorphic levels in northern European populations. Because persons carrying the allele absorb iron more readily than do noncarriers, it has often been suggested that HFE is an adaptation to anemia. We hypothesize positive selection for HFE began during or after the European Neolithic with the adoption of an iron-deficient high-grain and dairying diet and consequent anemia, a finding confirmed in Neolithic and later European skeletons. HFE frequency compared with rate of lactase persistence in Eurasia yields a positive linear correlation coefficient of 0.86. We suggest this is just one of many mutations that became common after the adoption of agriculture.

Coagulation, flocculation, and denaturation: a century of research into protoplasmic theories of anesthesia.

Within two decades of the discovery of anesthesia, the physicochemical concept of colloid and the biological concept of protoplasm had emerged. Fusion of these concepts into a theoretical framework, which has been largely forgotten decades ago, promised to uncover fundamental biological truths and determined research into anesthetic mechanisms for a century after "Ether Day." Observations of optical changes in unstained tissue were condensed into a theory of anesthesia by coagulation of protoplasm in the 1870s. The underlying hypotheses, conformational changes of proteins within the protoplasm cause all behavioral effects of anesthesia, continued to be pursued well into the 20th century. The goal was to explain anesthesia using physical chemistry within a fundamental cell biological framework. This large body of work, swept aside during the decades of lipid membrane hegemony, has remained in obscurity even after proteins in excitable membranes became firmly established as mediators of the immediate anesthetic effects. This article is a reminder of the prolonged interdisciplinary research effort dedicated to "protoplasmic theories" at a time when attention is increasingly directed toward examining the nature of (un)consciousness well as noncanonical consequences of anesthetic exposure that are not easily accounted for within conventional pharmacological concepts.

The origins of the molecular era of adhesion research.

Recognition of the importance of cell adhesion grew steadily during the twentieth century as it promised answers to fundamental questions in diverse fields that included cell biology, developmental biology, tumorigenesis, immunology and neurobiology. However, the route towards a better understanding of its molecular basis was long and difficult, with many false starts. Major progress was made in the late 1970s to late 1980s with the identification of the major families of adhesion molecules, including integrins and cadherins. This in turn set the stage for the explosive growth in adhesion research over the past 25 years.

Hemochromatosis: discovery of the HFE gene.

Hereditary hemochromatosis (HH) is a common inherited disorder of iron metabolism affecting about 1 in 250 individuals. HH results in an increased absorption of iron at the baso-lateral surface of the enterocyte with aberrant regulation of ferroportin-mediated transfer of iron in turn brought on by a decrease in circulating hepcidin. The medical literature describes a colorful history of HH with important contributions from faculty at Saint Louis University.

The life and work of Shoichiro Tsukita.

We dedicate the 2008 Berlin conference and this collection of scientific manuscripts to the memory of our colleague Shoichiro Tsukita. His seminal scientific contributions and impact on the field of tight junctions is substantial. Shoichiro was a professor at Kyoto University and one the world's most influential biologists when he passed away on December 11, 2005 at the age of 52 from complications of pancreatic cancer. He was a pioneer in several areas of cell biology; most particularly he will be remembered as the founding father of the molecular study of tight junctions.

Shoichiro Tsukita: a life exploring the molecular architecture of the tight junction.

On December 11, 2005, Shoichiro Tsukita died at the young age of 52, after 14 months of treatment for cancer. Early in his career, Tsukita succeeded in isolating and purifying the adherens junction with his wife Sachiko, an accomplishment that he followed up with an impressive series of discoveries of cell adhesion and cytoskeletal molecules, including what may have been his greatest contribution to the field, the identification of occludin and the claudin family of molecules, which were watershed discoveries in the study of the molecular nature of tight junctions.

Historical review: a brief history and personal retrospective of seven-transmembrane receptors.

Pharmacologists have studied receptors for more than a century but a molecular understanding of their properties has emerged only during the past 30-35 years. In this article, I provide a personal retrospective of how developments and discoveries primarily during the 1970s and 1980s led to current concepts about the largest group of receptors, the superfamily of seven-transmembrane (7TM) receptors [also known as G-protein-coupled receptors (GPCRs)]. Significant technical advances such as the development of methods for radioligand binding, solubilization and purification of the beta(2)-adrenoceptor and other adrenoceptors led to the cloning of receptor genes and the discovery of their 7TM architecture and homology with rhodopsin. A universal mechanism of receptor regulation by G-protein-coupled receptor kinases (GRKs) and arrestins, originally discovered as a means of "desensitizing" G-protein-mediated second-messenger generation, was subsequently found to mediate both receptor endocytosis and activation of a growing list of signaling pathways such as those involving mitogen-activated protein kinases. Numerous opportunities for novel therapeutics should emerge from current and future research on 7TM receptor biology.

Lipids on the frontier: a century of cell-membrane bilayers.

Our present picture of cell membranes as lipid bilayers is the legacy of a century's study that concentrated on the lipids and proteins of cell-surface membranes. Recent work is changing the picture and is turning the snapshot into a video.