Paradise revealed II: Top science, sunny beach, tropical fruits and caipirinhas….

Abstract

Some people say that lightning never strikes twice in the same place. Gratefully, sunbeam does! In February 2010, Brazilian scientists organized an outstanding multidisciplinary meeting at a beach resort in Angra dos Reis, Rio de Janeiro, Brazil, that brought together leaders of the cell death, tumor biology and immunology fields. Along with couple of hundred participants, speakers shared their latest work, experience and enthusiasm in an excited atmosphere rocked by the sound of waves.1 Keystone Symposia on Molecular and Cellular Biology and Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), the Sao Paulo State Research Foundation, decided to surf this idea and worked together to implement the first Keystone meeting in the State of Sao Paulo—the second organized in Brazil. This time the venue was the delightful Enseada beach, in Guaruja, a coastal paradisiacal town located in the south of the State of Sao Paulo. The sophisticated and yet casual hotel, the amazing fine sand beach, the fresh breeze, the tasty fruits and coconut water and, of course, the famous Brazilian caipirinhas provided an incredibly relaxed and friendly atmosphere where top scientists were overwhelmed by the quality and depth of students' interrogations. Organized by Gustavo Amarante-Mendes, Douglas Green and Kim Newton, the event started with a pre-meeting course on Cell Death modalities. The course brought together 60 PhD students or postdocs fully supported by FAPESP, half coming from Brazil and half from abroad, creating a dynamic and highly interactive environment that lasted throughout the meeting. Vishva Dixit (Genentech, Inc., USA) presented the 'Keynote Address' on inflammasome structure and signaling events, describing the activation of non-canonical inflammasome by cytosolic LPS and its role in septic shock. In line with this, Petr Broz (University of Basel, Switzerland) demonstrated that guanylate-binding proteins (GBPs) targeted the bacteria and promoted disruption of bacteria-containing vacuoles, allowing cytosolic sensing of LPS and caspase-11 activation. Guy Salvesen (Sanford-Burnham Medical Research Institute, USA) introduced us to novel specific probes highly specific for each caspase active site, enabling unambiguous discrimination of caspase activation. Mohanish Deshmukh (University of North Carolina at Chapel Hill, USA) demonstrated that cytosolic cytochrome c is not able to engage in the apoptosome formation in neurons because of very low levels of Apaf-1 in these cells, and that free cytosolic cytochrome c is ubiquitinated and degraded by the proteasome. Marion MacFarlane (MRC Toxicologic Unit, UK), demonstrated that caspase-8 and c-FLIP were able to form chains, and that the respective ratio of caspase-8/c-FLIPS/L determines whether the cell would engage the apoptotic pathway or rather continue to live. Necroptotic pathways were extensively discussed by Peter Vandenabeele (VIB, Ghent University, Belgium), Francis Chan (University of Massachussets Medical School, USA) and Kim Newton (Genentech, Inc., USA). Peter Vandenabeele described that RIPK1 protects intestinal epithelial cells (IECs) from apoptosis. RIPK1IEC-KO mice presented increased apoptosis, barrier disruption, bacterial translocation and inflammatory infiltrates, resulting in significant weight loss and lethality. Importantly, antibiotic treatment of RIPK1IEC-KO mice decreased the inflammation and improved survival. Francis Chan revealed that, in dendritic cells, RIPK3 is necessary for TLR4-mediated activation of caspases-8 (requirement for FADD and RIPK1) and -1 (requirement for ROS) and IL-1β processing, and that RIPK3-mediated maturation of IL-1β is critical to injury-induced tissue repair. Kim Newton described that necroptosis-related inflammation is dependent on RIPK1 and RIPK3, but not on MLKL. Douglas Green (St Jude Children's Research Hospital, USA) delivered a captivating lecture in which he approached the question of non-genetic control of cell survival. He presented new results obtained by single-cell mass spectrometry to investigate the cell population that consistently survives TRAIL-induced apoptosis.