ERC FUNDED PROJECTS

Therapeutic modulation of vascular cell proliferation and migration is essential for the effective inhibition of angiogenesis in cancer or its induction in cardiovascular disease. The current view is that an increase in growth factor levels or mitogenic stimulation is beneficial for angiogenesis, since it leads to an increase in both endothelial proliferation and sprouting. Through the use of innovative genetic and imaging approaches, we have recently elucidated a previously unappreciated, context-dependent mechanism whereby highly mitogenic environments can be detrimental for angiogenesis and lead to the cell-cycle arrest of endothelial cells (ECs), which ultimately impairs vascular growth. The identified mechanism may explain the failed or inefficient promotion of functional angiogenesis by vascular growth factor delivery therapies, such as those used to treat ischemic cardiovascular disease. We propose that a better understanding and modulation of the identified hypermitogenic arrest process may allow angiogenesis to be induced more effectively. Taking advantage of recent advances in DNA synthesis, CRISPR gene editing, microscopy and single-cell profiling technologies, we have developed new genetic tools, animal models and methods of broad relevance that enable the study of gene function with higher reliability, throughput and definition. We propose to use these novel research tools and methods to significantly increase understanding of the biology of blood vessels in distinct physiological and pathological contexts. We will then use this new knowledge to identify better strategies to promote vascular development in ischemic cardiovascular disease, heal vascular malformations, or inhibit angiogenesis in tumours.

1 998 500 €

Start date: 2021-03-01, End date: 2026-02-28

European incursions onto the narrow isthmian pass that divided and connected the Atlantic and Pacific oceans made it a strategic node of the Spanish Empire and a crucial site for early modern globalization. On the front lines of the convergence of four continents, Old Panama offers an unusual opportunity for examining the diverse, often asymmetrical impacts of cultural and commercial contacts. The role of Italian, Portuguese, British, Dutch, and French interests in the area, as well as an influx of African slaves and Asian merchandise, have left a unique material legacy that requires an integrated, interdisciplinary approach to its varied sources. Bones, teeth and artifacts on this artery of Empire offer the possibility of new insights into the cultural and biological impact of early globalization. They also invite an interdisciplinary approach to different groups’ tactics for survival, including possible dietary changes, and the pursuit of profit. Such strategies may have led the diverse peoples inhabiting this junction, from indigenous allies to African and Asian bandits to European corsairs, to develop and to favor local production and Pacific trade networks at the expense of commerce with the metropolis. This project applies historical, archaeological and archaeometric methodologies to evidence of encounters between peoples and goods from Europe, America, Africa and Asia that took place on the Isthmus of Panama during the sixteenth and seventeenth centuries. Forging an interdisciplinary approach to early globalization, it challenges both Euro-centric and Hispano-phobic interpretations of the impact of the conquest of America, traditionally seen as a demographic catastrophe that reached its nadir in the so-called seventeenth-century crisis. Rather than applying quantitative methods to incomplete source material, researchers will adopt a contextualized, inter-disciplinary, qualitative approach to diverse agents involved in cultural and commercial exchange.

1 998 875 €

Start date: 2016-01-01, End date: 2021-06-30

One of the remaining primary challenges in modern chemistry is the development of clean, energy- and cost-efficient catalytic processes that can allow to convert simple and abundant chemical feedstocks into high value-added products. Given the vast reserves of methane from natural gas, available worldwide, the direct use of the simplest alkane as source of fuels and chemicals could have a great impact in our society. However, methane´s low intrinsic reactivity has rendered its use extremely difficult for purposes beyond aerobic combustion and the production of syngas. Despite some recent advances in the field, a general strategy for a diverse and versatile use of methane is elusive. The overall aim of this proposal is the development of a new paradigm in catalysis which can provide new catalytic processes that allow direct methane functionalization by using it as a methylating reagent in a variety of C-C bond forming reactions. The approach described in this proposal is based on a cooperative interaction between two transition metal complexes in which an early transition metal is responsible for the methane C-H activation and a late transition metal is the actual catalyst of the methylation process. The link between these two processes is a transmetalation step and will be used to transfer the mechanism of typical cross-coupling reactions to the field of methane functionalization. New pathways for the direct use of methane in reactions such as allylic alkylation, conjugate addition, cross-coupling, C-H methylation and alkene hydromethylation will be developed based on this novel bimetallic catalytic strategy. It is envisioned that the proposed research will lead to a new concept at the interface of catalytic cross coupling reactions and C-H activation. It will contribute to the fundamental understanding of these two reactions and will provide the basis for a new technology for energy efficient and environmentally friendly, thus sustainable, methane conversion.

1 999 679 €

Start date: 2020-09-01, End date: 2025-08-31

The global marine ecosystem is being deeply altered by human activity. On the one hand, rising concentrations of atmospheric greenhouse gases are changing the physical and chemical state of the ocean, exerting pressure from the bottom up. Meanwhile, the global fishery has provided large economic benefits, but in so doing has restructured ecosystems by removing most of the large animal biomass, a major top-down change. Although there has been a tremendous amount of research into isolated aspects of these impacts, the development of a holistic understanding of the full interactions between physics, chemistry, ecology and economic activity might appear impossible, given the myriad complexities. This proposal lays out a strategy to assemble a team of trans-disciplinary expertise, that will develop a unified, data-constrained, grid-based modeling framework to represent the most important interactions of the global human-ocean system. Building this framework requires solving a series of fundamental problems that currently hinder the development of the full model. If these problems can be solved, the resulting model will reveal novel emergent properties and open the doors to a range of previously unexplored questions of high impact across a range of disciplines. Key questions include the ways in which animals interact with oxygen minimum zones with implications for fisheries, the impacts fish harvesting may have on nutrient recycling, spatio-temporal interactions between managed and unmanaged fisheries, and fundamental questions about the relationships between fish price, fishing cost, and multiple markets in a changing world. Just as the first coupled ocean-atmosphere models revealed a wealth of new behaviours, the coupled human-ocean model proposed here has the potential to launch multiple new fields of enquiry. It is hoped that the novel approach will contribute to a paradigm shift that treats human activity as one component within the framework of the Earth System.

1 600 000 €

Start date: 2016-07-01, End date: 2021-12-31