ERC FUNDED PROJECTS

The mechanism of cell division is conserved in many eukaryotes, from yeast to man. A contractile ring of filamentous actin and myosin II motors generates the force to bisect a mother cell into two daughters. The actomyosin ring is among the most complex cellular machines, comprising over 150 proteins. Understanding how these proteins organize themselves into a functional ring with appropriate contractile properties remains one of the great challenges in cell biology. Efforts to generate a comprehensive understanding of the mechanism of actomyosin ring assembly have been hampered by the lack of structural information on the arrangement of actin, myosin II, and actin modulators in the ring in its native state. Fundamental questions such as how actin filaments are assembled and organized into a ring remain actively debated. This project will investigate key issues pertaining to cytokinesis in the fission yeast Schizosaccharomyces pombe, which divides employing an actomyosin based contractile ring, using the methods of genetics, biochemistry, cellular imaging, DNA origami, genetic code expansion, and click chemistry. Specifically, we will (1) attempt to visualize actin filament assembly in live cells expressing fluorescent actin generated through synthetic biological approaches, including genetic code expansion and click chemistry (2) decipher actin filament polarity in the actomyosin ring using total internal reflection fluorescence microscopy of labelled dimeric and multimeric myosins V and VI generated through DNA origami approaches (3) address when, where, and how actin filaments for cytokinesis are assembled and organized into a ring and (4) reconstitute actin filament and functional actomyosin ring assembly in permeabilized spheroplasts and in supported bilayers. Success in the project will provide major insight into the mechanism of actomyosin ring assembly and illuminate principles behind cytoskeletal self-organization.

2 863 705 €

Start date: 2015-11-01, End date: 2020-10-31

The current trend in biophotonics is to try and replicate the same ease and precision that our hands, eyes and ears offer at the macroscopic level, e.g. to hold, observe, squeeze and pull, rotate, cut and probe biological specimens in microfluidic environments. The bidding to get closer and closer to the object of interest has prompted the development of extremely advanced manipulation techniques at scales comparable to that of the wavelength of light. However, the fact that the optical beam can only access the microfluidic chip from the narrow aperture of a microscopic objective limits the versatility of the photonic function that can be realized. With this project, the applicant proposes to introduce a new biophotonic platform based on the all optical manipulation of flexible photonic metasurfaces. These artificial two-dimensional materials have virtually arbitrary photonic responses and have an intrinsic exceptional mechanical stability. This cross-disciplinary project, bridging photonics, material sciences and biology, will enable the adoption of the most modern and advanced photonic designs in microfluidic environments, with transformative benefits for microscopy and biophotonic applications at the interface of molecular and cell biology.

1 999 524 €

Start date: 2019-02-01, End date: 2024-01-31

"This proposal addresses major questions in particle physics that are at the forefront of experimental and theoretical physics research today. The results offered would have far-reaching implications in other fields such as cosmology and could help answer some of the big questions such as why the universe contains so much more matter than antimatter. The research objectives of this proposal are to (i) make world-leading tests of CPT symmetry and (ii) discover the neutrino mass hierarchy and search for indications of leptonic CP violation. The NOvA long-baseline neutrino oscillation experiment will use a novel ""totally active scintillator design"" for the detector technology and will be exposed to the world's highest power neutrino beam. Building on the first direct observation of muon antineutrino disappearance (that was made by a group founded and led by the PI at the MINOS experiment), tests of CPT symmetry will be performed by looking for differences in the mass squared splittings and mixing angles between neutrinos and antineutrinos. The potential to discover the mass hierarchy is unique to NOvA on the timescale of this proposal due to the long 810 km baseline and the well measured beam of neutrinos and antineutrinos. This proposal addresses several key challenges in a long-baseline neutrino oscillation experiment with the following tasks: (i) development of a new approach to event energy reconstruction that is expected to have widespread applicability for future neutrino experiments; (ii) undertaking a comprehensive calibration project, exploiting a novel technique developed by the PI, that will be essential to achieving the physics goals; (iii) development of a sophisticated statistical analyses. The results promised in this proposal surpass the sensitivity to antineutrino oscillation parameters of current 1st generation experiments by at least an order of magnitude, offering wide scope for profound discoveries with implications across disciplines."

1 415 848 €

Start date: 2012-10-01, End date: 2018-09-30

Imagine being able to design into living cells and organisms de novo vesicle transport mechanisms that do not naturally exist? At one level this is a wild-eyed notion of synthetic biology. But we contend that this vision can be approached even today, focusing first on the process of exocytosis, a fundamental process that impacts almost every area of physiology. Enough has now been learned about the natural core machinery (as recognized by the award of the 2013 Nobel Prize in Physiology or Medicine to the PI and others) to take highly innovative physics/engineering- and DNA-based approaches to design synthetic versions of the secretory apparatus that could someday open new avenues in genetic medicine. The central idea is to introduce DNA-based functional equivalents of the core protein machinery that naturally form (coats), target (tethers), and fuse (SNAREs) vesicles. We have already taken first steps by using DNA origami-based templates to produce synthetic phospholipid vesicles and complementary DNA-based tethers to specifically capture these DNA-templated vesicles on targeted bilayers. Others have linked DNA oligonucleotides to trigger vesicle fusion. The next and much more challenging step is to introduce such processes into living cells. We hope to break this barrier, and in the process start a new field of research into “synthetic exocytosis”, by introducing Peptide-Nucleic Acids (PNAs) of tethers and SNAREs to re-direct naturally-produced secretory vesicles to artificially-programmed targets and provide artificially-programmed regulation. PNAs are chosen mainly because they lack the negatively charged phosphate backbones of DNA, and therefore are more readily delivered into the cell across the plasma membrane. Future steps, would include producing the transport vesicles synthetically within the cell by externally supplied origami-based PNA or similar cages, and - much more speculatively - ultimately using encoded DNA and RNAs to provide these functions.

3 000 000 €

Start date: 2015-09-01, End date: 2021-08-31