Abstract: The pleiotropic factor TGFbeta is a major tumor suppressor but also key regulator of epithelial to mesenchymal transition (EMT) and remodeling of the extracellular matrix (ECM) fostering tumor progression. The molecular mechanisms controlling these different functionalities remain poorly understood and it is widely believed that the cell context is decisive. In lung cancer, one of the deadliest cancer entities, increased TGFbeta levels have been associated with poor outcome and thus there is an urgent, unmet clinical need to resolve the molecular impact of TGFbeta. By a global proteomics approach, we demonstrate that the level of the TGFbeta type I and type II receptors is highly variable whereas the core components of the signaling pathway remain rather stable. Furthermore, dynamic pathway modeling of the TGFbeta induced canonical SMAD signaling cascade provides evidence that the TGFbeta receptors are the most sensitive regulatory node. Accordingly, we developed a targeted mass spectrometry-based approach and show that the amounts of the TGFbeta receptors greatly differ in lung cancer cell lines and confirm this observation in lung adeno carcinoma patients. Our results point to a critical role of the abundance of TGFbeta receptors and to an association with lung cancer recurrence.

Abstract: The ocean is the largest ecosystem on Earth and yet we know very little about it. This is particularly true for the plankton that drift within, even though they form the base of marine food webs and are key players in Earth’s biogeochemical cycles. Ocean plankton are at least as important for the Earth system as the forests on land, but most of them are invisible to the naked eye and thus are largely uncharacterized. To increase our understanding of this underexplored world, a multidisciplinary consortium, Tara Oceans, was formed around the 36m research schooner Tara, which sampled plankton at more than 210 sites and multiple depth layers in all the major oceanic regions during expeditions from 2009-2013 (Karsenti et al. Plos Biol., 2011). This talk will summarize the foundational resources from the project, which collectively represent the largest DNA sequencing effort for the oceans (see Science special issue May 22, 2015 and Cell, Nov 14, 2019), and analyses that illustrate several aspects of the Tara Oceans’ eco-systems biology approach to address microbial contributions to ecological and evolutionary processes. The project provides unique resources for several scientific disciplines that are foundational for mapping ocean biodiversity of a wide range of organisms that are rarely studied together, exploring their interactions, and integrating biology into our physico-chemical understanding of the ocean, as well as for identifying new organisms and genes of biotechnological interest. These resources, and the scientific innovations emerging to understand them, are furthermore critical towards developing baseline ecological context and predictive power needed to track the impact of climate change on the ocean.

Abstract: As technologies in our industry advance in complexity, speed, sensitivity and ease of use, the opportunity to use multiple approaches to answer high-dimensional biological questions is changing and expanding our knowledge of immunology. To expand growth and future in our field, the combined use of high-parameter analytical and sorting flow cytometry instruments, imaging flow cytometry, advanced spectral cytometry, deep proteomic databases, and advanced single-cell multiomic tools (proteomic and genomic) will help define new functional biomarkers needed to facilitate a better understanding of the complexities of immune health and disease.