ERC FUNDED PROJECTS

In mammals, gene dosage of X-chromosomal genes is equalized between sexes by random inactivation of either one of the two X chromosomes in female cells. In the initial phase of X chromosome inactivation (XCI), a counting and initiation process determines the number of X chromosomes per nucleus, and elects the future inactive X chromosome (Xi). Xist is an X-encoded gene that plays a crucial role in the XCI process. At the start of XCI Xist expression is up-regulated and Xist RNA accumulates on the future Xi thereby initiating silencing in cis. Recent work performed in my laboratory indicates that the counting and initiation process is directed by a stochastic mechanism, in which each X chromosome has an independent probability to be inactivated. We also found that this probability is determined by the X:ploïdy ratio. These results indicated the presence of at least one X-linked activator of XCI. With a BAC screen we recently identified X-encoded RNF12 to be a dose-dependent activator of XCI. Expression of RNF12 correlates with Xist expression, and a heterozygous deletion of Rnf12 results in a marked loss of XCI in female cells. The presence of a small proportion of cells that still initiate XCI, in Rnf12+/- cells, also indicated that more XCI-activators are involved in XCI. Here, we propose to investigate the molecular mechanism by which RNF12 activates XCI in mouse and human, and to search for additional XCI-activators. We will also attempt to establish the role of different inhibitors of XCI, including CTCF and the pluripotency factors OCT4, SOX2 and NANOG. We anticipate that these studies will significantly advance our understanding of XCI mechanisms, which is highly relevant for a better insight in the manifestation of X-linked diseases that are affected by XCI.

1 500 000 €

Start date: 2011-04-01, End date: 2016-03-31

The discoveries that the expansion of the universe is accelerating due to an unknown “dark energy” and that most of the matter is invisible, highlight our lack of understanding of the major constituents of the universe. These surprising findings set the stage for research in cosmology at the start of the 21st century. The objective of this proposal is to advance observational constraints to a level where we can distinguish between physical mechanisms that aim to explain the properties of dark energy and the observed distribution of dark matter throughout the universe. We use a relatively new technique called weak gravitational lensing: the accurate measurement of correlations in the orientations of distant galaxies enables us to map the dark matter distribution directly and to extract the cosmological information that is encoded by the large-scale structure. To study the dark universe we will analyse data from a new state-of-the-art imaging survey: the Kilo- Degree Survey (KiDS) will cover 1500 square degrees in 9 filters. The combination of its large survey area and the availability of exquisite photometric redshifts for the sources makes KiDS the first project that can place interesting constraints on the dark energy equation-of-state using lensing data alone. Combined with complementary results from Planck, our measurements will provide one of the best views of the dark side of the universe before much larger space-based projects commence. To reach the desired accuracy we need to carefully measure the shapes of distant background galaxies. We also need to account for any intrinsic alignments that arise due to tidal interactions, rather than through lensing. Reducing these observational and physical biases to negligible levels is a necessarystep to ensure the success of KiDS and an important part of our preparation for more challenging projects such as the European-led space mission Euclid.

1 316 880 €

Start date: 2012-01-01, End date: 2016-12-31

This research proposal explores the political economy of international development assistance (aid) directed towards social expenditures, examined through the lens of a particular financial quandary that has been ignored in the literature despite having important economic and political repercussions. The quandary is that aid cannot be directly spent on expenditures denominated in domestic currency. Instead, aid needs to be first converted into domestic currency whereas the foreign exchange provided is used for other purposes, resulting in a process prone to complex politics regarding domestic monetary policy and spending commitments. The implications require a serious rethink of many of the accepted premises in the political economy of aid and related literatures. It is urgent to engage in this rethinking given tensions between two dynamics in the current global political economy: a tightening financial cycle facing developing countries versus an increasing emphasis in international development agendas of directing aid towards social expenditures. The financial quandary might exacerbate these tensions, restricting recipient government policy space despite donor commitments of respecting national ownership. The proposed research examines these implications through the emerging social protection agenda among donors, which serves as an ideal policy case given that social protection expenditures are almost entirely based on domestic currency. This will be researched through a mixed-method comparative case study of six developing countries, combining quantitative analysis of balance of payments and financing constraints with qualitative process tracing based on elite interviews and documentary research. The objective is to re-orient our thinking on these issues for a deeper appreciation of the systemic political and economic challenges facing global redistribution towards poorer countries, particularly with respect to the forthcoming Sustainable Development Goals.

1 459 529 €

Start date: 2015-05-01, End date: 2021-05-31

Amazon forests contribute vital ecosystem services, including maintaining biodiversity (>10,000 tree species) and storing large amounts of carbon. Amazonia also features prominently in global climate, carbon, and vegetation models, which assume tropical forests are effectively pristine and that past human disturbance mimicked natural processes. It is now evident that recurrent human disturbance of Amazonia, like fire and deforestation, were significant in some areas. Since those disturbances likely modify subsequent vegetation dynamics - including temporarily increasing forest capacity to absorb carbon - the emerging paradigm of human disturbance is a challenge to global ecological understanding. The focus of my project is thus to reliably determine whether human disturbances occurred in locations that form the basis of global models. A key expected outcome is to either legitimize or force revision to these models of carbon sequestration potential in Amazonia. I will innovatively integrate ecological, paleoecological, archaeological, chemical and biogeographic analyses to assess the degree to which past human disturbance drives the diversity patterns and carbon dynamics observed in modern Amazonian forests. For key long-term sites across Amazonia, I will quantify the: i) time since the last fire, ii) past fire frequency, extent and intensity, iii) past vegetation change in the presence and absence of human activity, and iv) continuity of past human activity over the last 1000 years. My results will provide the first quantification of local-scale recovery processes exceeding 100 years in tropical forests, and will determine if observed forest dynamics are driven by disturbances that occurred before modern ecological surveys began. I will then quantify the extent to which past disturbances create an overestimation of carbon storage potential, driving a profound reexamination of carbon sequestration and biodiversity patterns in Amazonia.

1 481 378 €

Start date: 2020-01-01, End date: 2024-12-31