ERC FUNDED PROJECTS

"Eukaryotic nuclei are organised into functional compartments, – local microenvironments that are enriched in certain molecules or biochemical activities and therefore specify localised functional outputs. Our study seeks to unveil fundamental principles of co-regulation of genes in a chromo¬somal compartment and the preconditions for homeostasis of such a compartment in the dynamic nuclear environment. The dosage-compensated X chromosome of male Drosophila flies satisfies the criteria for a functional com¬partment. It is rendered structurally distinct from all other chromosomes by association of a regulatory ribonucleoprotein ‘Dosage Compensation Complex’ (DCC), enrichment of histone modifications and global decondensation. As a result, most genes on the X chromosome are co-ordinately activated. Autosomal genes inserted into the X acquire X-chromosomal features and are subject to the X-specific regulation. We seek to uncover the molecular principles that initiate, establish and maintain the dosage-compensated chromosome. We will follow the kinetics of DCC assembly and the timing of association with different types of chromosomal targets in nuclei with high spatial resolution afforded by sub-wavelength microscopy and deep sequencing of DNA binding sites. We will characterise DCC sub-complexes with respect to their roles as kinetic assembly intermediates or as representations of local, functional heterogeneity. We will evaluate the roles of a DCC- novel ubiquitin ligase activity for homeostasis. Crucial to the recruitment of the DCC and its distribution to target genes are non-coding roX RNAs that are transcribed from the X. We will determine the secondary structure ‘signatures’ of roX RNAs in vitro and determine the binding sites of the protein subunits in vivo. By biochemical and cellular reconstitution will test the hypothesis that roX-encoded RNA aptamers orchestrate the assembly of the DCC and contribute to the exquisite targeting of the complex."

2 482 770 €

Start date: 2012-02-01, End date: 2017-01-31

BEACON aims at performing an ambitious multi-disciplinary (optical, radio astronomy and theoretical physics) study to enable a fundamentally improved understanding of gravitation and space-time. For almost a century Einstein's general relativity has been the last word on gravity. However, superstring theory predicts new gravitational phenomena beyond relativity. In this proposal I will attempt to detect these new phenomena, with a sensitivity 20 times better than state-of-the-art attempts. A successful detection would take physics beyond its current understanding of the Universe. These new gravitational phenomena are emission of dipolar gravitational waves and the violation of the strong equivalence principle (SEP). I plan to look for them by timing newly discovered binary pulsars. I will improve upon the best current limits on dipolar gravitational wave emission by a factor of 20 within the time of this proposal. I also plan to develop a test of the Strong Equivalence Principle using a new pulsar/main-sequence star binary. The precision of this test is likely to surpass the current best limits within the time frame of this proposal and then keep improving indefinitely with time. This happens because this is the cleanest gravitational experiment ever carried out. In order to further these goals, I plan to build the ultimate pulsar observing system. By taking advantage of recent technological advances in microwave engineering (particularly sensitive ultra-wide band receivers) digital electronics (fast analogue-to-digital converters and digital spectrometers) and computing, my team and me will be able to greatly improve the sensitivity and precision for pulsar timing experiments and exploit the capabilities of modern radio telescopes to their limits. Pulsars are the beacons that will guide me in these new, uncharted seas.

1 892 376 €

Start date: 2011-09-01, End date: 2016-08-31

Biofuel from wood and waste will be a substantial share of our future energy mix. The conversion of lignocellulose to fermentable polysaccharides is the current bottleneck. We propose to use single molecule cut and paste technology to assemble designer cellulosoms and combine enzymes from different species with nanocatalysts.

2 351 450 €

Start date: 2012-03-01, End date: 2018-02-28

Timing is everything in ecology, and because plants provide the foundation for most land-based food webs, the timing of their activities profoundly orchestrates the majority of ecological interactions. Most photosynthetic and growth processes are under circadian control, but many additional processes--approximately 30-40% of all genes—are under circadian control, and yet the Darwinian fitness impact of being “in synch” with the environment has not been systematically studied for any organism. We have developed a toolbox for a native tobacco plant, Nicotiana attenuata, that allows us to “ask the plant” which genes, proteins or metabolites are regulated in particular plant-mediated ecological interactions; identify “the genes that matter” for a given interaction; silence or ectopically express these genes, and conduct field releases with the transformed plants at a nature preserve in the Great Basin Desert to rigorously test hypotheses of gene function. By taking advantage of both our understanding of what it takes for this plant to survive in nature, and the procedures established to disentangle the skein of subtle interactions that determine its performance, we will systematically examine the importance of synchronous entrained endogenous rhythms at all life stages: longevity in the seed bank, germination, rosette growth, elongation, flowering and senescence. Specifically, we propose to silence a key components (starting with NaTOC1) of the plant’s endogenous clock to shorten the plant’s circadian rhythm, both constitutively and with strong dexamethasone-inducible promoters, at all life stages. With a combination of real-time phenotype imaging, metabolite and transcriptome analysis, and ecological know-how, the research will reveal how plants adjust their physiologies to the ever-changing panoply of environmental stresses with which they must cope; by creating arrhythmic plants, we will understand why so many processes are under circadian control.

2 496 002 €

Start date: 2012-04-01, End date: 2017-03-31