Paradise revealed: first-class science rocked by the sound of the waves

Abstract

Paradise certainly comes in many different flavors in the mind of each individual. Well, many of these flavors were recently combined at a beach resort south of the city of Rio de Janeiro, Brazil, where the first meeting on ‘Signaling in Cell Death, Cancer and the Immune System’ was held, creating an incredible atmosphere of intellectuality, joy and friendship. There, first-class scientists shared their most recent work and insights with an enthusiastic group of young scientists and graduate students. Around 200 people gathered at the conference and poster section rooms, the overflowing restaurant or the surroundings of a complex of swimming pools and bars. Seasoning the intense scientific discussions were the spectacular view of the ocean, fine sand beach, coconut water and caipirinhas! The aim of this meeting was to put together a multi disciplinary scientific program with focus on signaling trans duction that could gather scientists from the fields of cell death, tumor biology and immunology. As you will be able to appreciate from the next paragraphs, the results were outstanding. The meeting started with a symposium that highlighted novel mechanisms operating in cell death, cancer and innate immunity. Seamus Martin (Trinity College Dublin, Ireland) revealed a novel p53-independent, ERK-regulated pathway responsible for the induction of a proapoptotic member of the Bcl-2 family, namely NOXA, important for the chemother apeutic properties of platinum compounds. Scott Lowe (Howard Hughes Medical Institute and Cold Spring Harbor Laboratory, USA) put forward powerful global genetic approaches based on ex vivo manipulation of stem cells, in particular with libraries of shRNA, followed by transplantation of these cells to syngeneic recipient mice. As a consequence, his team can now create mosaic mouse models to study the role of tumor suppression genes and the cell death machinery in tumor maintenance or regression. Luke O’Neill (Trinity College Dublin, Ireland) showed that the small G protein Rab39a seems to contain a putative caspase-1 cleavage site at D148. Because the removal of Rab39 from phagolyso somes is essential for its acidification and the knocking down of Rab39a inhibits IL-1b secretion but not TNF-a, O’Neill proposed that Rab39a functions as a traffic adapter linking caspase-1 to IL-1b secretion. Taking advantage of his innovative mind, Ruslan Medzhitov (Howard Hughes Medical Institute and Yale University School of Medicine, USA) presented the Keynote Lecture offering us his personal view about the formation and maintenance of tissues in multicellular organisms. Anchored in elegant results from his group as well as from others, he called our attention to the existence of a certain level of control of life and death in tissues based on the relative fitness of cells. Interestingly, less fitted or ‘loser’ cells are only eliminated in the presence of ‘winners’, suggesting the existence of a mechanism aiming to enhance body fitness, but that still preserves architecture and function of the less robust tissue. Passive competition takes place predominantly (or maybe only) during restrictive situations (stress, or limitations in space, growth factors, nutrients, etc.) and seems to be dependent on cell-intrinsic differences to react to the restrictive environment. A major player identified by Medzhitov and colleagues is p53, expression of which is higher in ‘loser’ than ‘winner’ cells. Active competition, however, is likely to be cell extrinsic and may occur at the steady/homeostatic state of a given tissue. ‘Winners’, in this case, may actively suppress or even kill the ‘losers’, and the ‘losers’ may even promote the growth of the ‘winners’. Importantly, in any of this situations, a complex set of communication signals appears to control the ‘social behavior of cells’, aspiring for a healthier organism. Also, at least at the cellular level, the Darwinian ‘survival of the fittest’ is based not only in competition, but also in cooperation and sacrifice.