ERC FUNDED PROJECTS

Female germ cells, oocytes, are highly specialised cells. They ensure the continuity of species by providing the female genome and mitochondria along with most of the nutrients and housekeeping machinery the early embryo needs after fertilisation. Oocytes are remarkable in their ability to survive for long periods of time, up to 50 years in humans, and retain the ability to give rise to a young organism while other cells age and die. Surprisingly little is known about oocyte dormancy. A key feature of dormant oocytes of virtually all vertebrates is the presence of a Balbiani body, which is a non-membrane bound compartment that contains most of the organelles in dormant oocytes and disappears as the oocyte matures. The goal of this proposal is to combine genetic and biochemical perturbations with imaging and the state of the art proteomics techniques to reveal the mechanisms dormant oocytes employ to remain viable. My previous research has shown that the Balbiani body forms an amyloid-like cage around organelles that could be protective. This has led me to identify the large number of unanswered questions about the cell biology of a dormant oocyte. In this proposal, we will study three of these questions: 1) What is the metabolic nature of organelles in dormant oocytes? 2) How does the Balbiani body disassemble and release the complement of organelles when oocytes start to mature? 3) What is the structure and function of the Balbiani body in mammals? We will use oocytes from two vertebrate species, frogs and mice, which are complementary for their ease of handling and relationship to human physiology. By studying the Balbiani body, this proposal will provide fundamental insights into organisation and function of organelles in oocytes and the regulation of physiological amyloid-like structures. More generally, the proposed experiments open up new avenues into the mechanisms that protect organelles from ageing and how oocytes stay dormant for many decades.

1 381 286 €

Start date: 2018-03-01, End date: 2023-02-28

This project aims to understand the role of effort in the reproduction of social inequality. While large-scale test programs like PISA have produced impressive amounts of data on the determinants of cognitive abilities, there is scant evidence on socio-economic differences in cognitive effort. Better understanding the social origins of effort pushes the frontier of knowledge on intergenerational mobility and allows improving equality of opportunity. Specifically, the aim of the project is to answer three research questions: 1. To what extent do children’s effort levels differ by parental socioeconomic background? (descriptive component). 2. Can existing disparities in effort by social background be explained by (a) the intergenerational transmission of effort from parents to children, and (b) varying motivations and differential susceptibility to incentives? (analytical component). 3. What are the best techniques to measure cognitive effort and what are the strengths and weaknesses of measures routinely used in different scientific disciplines? (methodological component). The project will develop and exploit cutting-edge methods of effort measurement such as real-effort tasks and psychophysiological techniques like pupillometry. Their immense potential has remained untapped in inequality research thus far. Experimental data will be collected for a large sample of school-age children and their parents in Spain and Germany. Subjective effort dispositions will be further analyzed using (inter)national surveys. The triangulation of carefully chosen methodologies will provide the first reliable evidence on socioeconomic differences in effort and stimulate new research (e.g. on gender or ethnic differentials in effort). Cross-validation analysis will detect possible biases of commonly used effort measures. The research findings will provide valuable insights for educational practitioners and decisive evidence for normative debates about social inequality and policy design.

1 499 572 €

Start date: 2018-03-01, End date: 2023-02-28

For many years, mitochondria were viewed as semiautonomous organelles, required only for cellular energetics. This view has been displaced by the concept that mitochondria are fully integrated into the life of the cell and that mitochondrial function and stress response rapidly affect other organelles, and even other tissues. A recent discovery from my lab demonstrated that mitochondrial metabolism regulates lysosomal degradation (Cell Metabolism, 2015), thus opening the way to investigate the mechanism behind communication between these organelles and its consequences for homeostasis. With this proposal, we want to assess how mitochondrial crosstalk with endolysosomal compartment controls cellular homeostasis and how mitochondrial dysfunction in certain tissues may account for systemic effects on the rest of the organism. EndoMitTalk will deliver significant breakthroughs on (1) the molecular mediators of endolysosomal-mitochondria communication, and how deregulation of this crosstalk alters cellular (2), and organism homeostasis (3). Our central goals are: 1a,b. To identify metabolic and physical connections mediating endolysosomal-mitochondria crosstalk; 2a. To decode the consequences of altered interorganelle communication in cellular homeostasis 2b. To study the therapeutic potential of improving lysosomal function in respiration-deficient cells; 3a. To assess how unresolved organelle dysfunction and metabolic stresses exclusively in immune cells affects organism homeostasis and lifespan. 3b. To decipher the molecular mediators by which organelle dysfunction in T cells contributes to age-associated diseases, with special focus in cardiorenal and metabolic syndromes. In sum, EndoMitTalk puts forward an ambitious and multidisciplinary but feasible program with the wide purpose of understanding and improving clinical interventions in mitochondrial diseases and age-related pathologies.

1 498 625 €

Start date: 2017-03-01, End date: 2022-02-28

This project aims to investigate the extent to which current trends in family formation, living arrangements and gender-specific education levels are related to the spatial distribution of welfare and the emergence of jobless households in contemporary societies. Inter alia, we aim to explore whether the welfare disequalizing, impoverishing and polarizing effects that are currently associated with recent patterns in assortative mating, lone parenthood and household composition are offset by an unprecedented phenomenon that is sweeping the world during the last decades: the rapid process education expansion in tandem with a reversal of the gender gap in education. The extent to which these two opposing forces occur and which of them is more influential in shaping the distribution of welfare between and within countries is among the main goals of this project. To this end, we will draw upon a variety of household surveys and the world largest sources of census microdata: the Integrated Public Use Microdata Series (IPUMS) project and the Latin American and Caribbean Demographic Centre. Because of their unparalleled geographical coverage and detail, these sources of data constitute exceptional instruments to study socio-demographic phenomena that have been vastly underutilized by the international research community. Triangulating our analysis at the micro, meso and macro levels, we will establish formal linkages between welfare distributions and its socio-demographic correlates to unveil insightful relationships that have been unsatisfactorily explored so far because of the lack of appropriately harmonized, sufficiently detailed and georeferenced datasets. We will strongly emphasize the spatial distribution of variables to unravel local patterns that might take place at highly disaggregated levels, therefore not being discernible to traditional (not as finely-grained) approaches.

1 174 500 €

Start date: 2015-05-01, End date: 2020-04-30