ERC FUNDED PROJECTS

"From scientific publications to the popular media, there have been numerous speculations about wirelessly controlled microrobots (microbots) navigating the human body. Microbots have the potential to revolutionize analytics, targeted drug delivery, and microsurgery, but until now there has not been any untethered microscopic system that could be properly moved let alone controlled in fluidic environments. Using glancing angle (physical vapor deposition) we will grow billions of micron-sized colloidal screw-propellers on a wafer. These chiral mesoscopic screws can be magnetized and moved through solution under computer control. The screw-propellers resemble artificial flagella and are the only ‘microbots’ to date that can be fully controlled in solution at micron length scales. The proposed work will advance the fabrication so that active microbots can be applied in rheological measurements and analytics. We will use these novel probes in bio-microrheology with the potential to probe the viscoelastic properties of membranes and tissues, and to explore questions of micro-hydrodynamics. At the same time we will develop these structures as ""colloidal molecules"" and grow asymmetric mesoscopic particles with tailored shapes and properties. We propose experiments that allow the observation of fundamental effects, such as chiral Brownian motion, something that exist at the molecular scale, but has never been observed to date. Similarly, we will be able to demonstrate for the first time chiral separations based purely on physical fields. The proposed technical advances of the growth of nanostructured surfaces will at the same time permit wafer-scale 3-D nano-structuring for photonic and plasmonic applications, which we plan to demonstrate. We will develop a system for targeted drug delivery, study the interaction of swarms of microbots and devise techniques to control and image these swarms."

1 479 760 €

Start date: 2012-02-01, End date: 2018-01-31

Nonsense-mediated mRNA decay (NMD) is an essential mechanism controlling translation in the eukaryotic cell. NMD ascertains accurate expression of the genetic information by quality controlling messenger RNA (mRNA). During translation, NMD factors recognize and target to degradation aberrant mRNAs that have a premature stop codon (PTC) and that would otherwise lead to the production of truncated proteins which could be harmful for the cell. A wide range of genetic diseases have their origin in the mechanisms of NMD. Discrimination of a PTC from a correct termination codon depends on splicing and translation, and it is the first and foremost step in human NMD. The molecular mechanism of this process remains elusive to date. In the research proposed, I will undertake to elucidate the molecular basis of translation termination and induction of NMD. I will study complexes involved in human translation termination at a normal stop codon and involved in NMD. I will employ an array of innovative techniques including recombinant production of human protein complexes by the MultiBac system, mammalian in vitro translation, mass spectrometry for detecting relevant protein modifications, biophysical techniques, mutational analyses and RNA-interference experiments. Stable ribosomal complexes with termination factors and complexes of NMD factors will be used for structure determination by cryo-electron microscopy. State-of-the-art image processing will be applied to address the inherent heterogeneity of the complexes. Hybrid approaches will allow the combination of cryo-EM structures with existing high-resolution structures of factors involved for generation of quasi-atomic models thereby visualizing molecular mechanisms of NMD action. This interdisciplinary work will foster our understanding at a molecular level of a paramount step in mRNA quality control, which is a vital prerequisite for the development of new treatment strategies in NMD-related diseases.

1 176 825 €

Start date: 2012-02-01, End date: 2016-11-30

Membrane proteins are coded by about 30% of the genes in the human genome and are primary targets for the action of drugs. I propose an interdisciplinary approach that will provide insight into the dynamic structure of membrane proteins of the outer mitochondrial membrane at unprecedented detail with respect to spatial resolution and time scale separation. Analysis of the dynamics and structure of membrane proteins is one of the biggest challenges in structural biology. I propose several new techniques mainly for solution NMR spectroscopy but also for solid-state NMR and electron paramagnetic resonance that go far beyond the state of art and enrich the sparse information from each of the individual techniques. The integration of complementary experimental information together with molecular dynamics simulations will push the description of the dynamic structure of membrane proteins to a new level. This new level is characterized by the possibility to determine structural ensembles of higher structural complexity and by access to dynamic time scales ranging from picoseconds to milliseconds. The characterization of motion is expected to establish the essential link between structure and function. The chosen outer mitochondrial membrane proteins are linked to several human pathologies that cannot be treated because structural and dynamic information at atomic resolution is missing. I expect that the novel insight into the dynamic structure of mitochondrial proteins will be critical to lay the basis for the development of novel, selective and improved therapies for cancer and age-related neurodegeneration.

1 496 200 €

Start date: 2011-11-01, End date: 2017-10-31

In this proposal a new electric field based approach for the control of magnetization dynamics is discussed. The advantage of using electric fields compared to magnetic fields is twofold: (i) electric fields are easy to confine in nano-structures (screening), and (ii) no current flow is required which may allow for the development of new spintronic devices with ultra low power consumption. Physically the application of an electric field to an ultrathin ferromagnetic material gives rise to modification of the wave-function overlap at the interface between a ferromagnetic metal and a dielectric. This electronic tuning causes a modified occupation of the d-orbitals at the interface and leads to electrically induced anisotropies. Hence external electric fields generate internal magnetic fields. Due to the modified orbital moment also a large voltage induced effect on the Gilbert damping is expected in magnetization dynamic experiments. In principle these fields can be applied even on ultrafast time scales. This will be explored when rf-electric fields are used to drive internal magnetic fields in the GHz frequency range to generate spin-waves. Furthermore this technique will be used to excite monochromatic spin-waves with wave-vectors well in the exchange dominated regime in order to study their propagation properties. I propose to use the spin-wave Doppler effect in order to break the intrinsic mirror symmetry required in for four-magnon scattering processes. In this way the resonance saturation may be tuned electrically to much larger values. Moreover electrically driven surface acoustic waves will be used to generate spin-waves which will be manipulated by an electric current using the spin-wave Doppler effect. The research described in the proposal is likely to have a large impact as a shift to electric field controlled spintronic devices is favorable on small length scales. In addition the power consumption of these devices may be reduced significantly.

1 495 860 €

Start date: 2012-01-01, End date: 2017-10-31