Funded Projects 2016
Inducing PrP misfolding by ribosomal frameshift caused by stable RNA structure formation of the PrP octapeptide region
Andreas Czech, Petr V. Konarev, Dmitri Svergun, Peter Wills, Zoya Ignatova
Creutzfeldt-Jakob disease (CJD) and scrapie are neurodegenerative diseases caused by the accumulation of the misfolded form (PrPSc) of cellular prion protein (PrPC). Albeit extensive research the initial misfolding mechanism is still elusive. It was hypothesized, that ribosomal frameshift during the translation of PrP mRNA might lead to PrP protein variants that initiate aggregation. What could cause this frameshift event, which under physiological conditions is very rare? We hypothesize, that either G-quadruplex, stable stem-loop formation or as also proposed earlier, RNA pseudoknot formation in the PrP mRNA leads to ribosomal stalling and consequently to frameshift. This results in an alternative PrP variant which at very low concentrations could induce misfolding and aggregation of cellular PrPC.
To check our hypothesis, we employ two strategies: First, we will assess the structure of the PrP mRNA by circular dichroism (CD) spectroscopy, absorption spectroscopy and small angle X-ray scattering (SAXS). Second, we use reporter constructs in human cell lines and in vitro lysates to measure the frequency of frameshift and the influence of RNA structure-modifying small molecules and ions.
Detection of resonant transitions within the quantum vacuum in the presence of a strong electromagnetic field
Anthony Hartin, Kensuke Homma, Ben King, Anton Ilderton
Our understanding of the physical vacuum is still relatively limited - it is one of the last great frontiers in physics. In classical physics, the vacuum is merely the unchanging background in which physical phenomena occur. However our understanding of nature is now a quantum one, and the quantum vacuum consists of a gas of virtual charges. When a strong electromagnetic field is present, the quantum vacuum starts to polarise. Theoretical studies of the quantum vacuum in the presence of a strong electromagnetic field predict resonant particle transitions within the part-polarised vacuum. It is as if the strong electromagnetic field sets up a quasi-energy level structure within the vacuum itself. In this project we will study these resonant vacuum transitions in detail, specifying resonance locations and widths, using a Quantum Field Theory which is non-perturbative with respect to the strong electromagnetic field. The aim of the project is to write a detailed experimental proposal, using parameters achievable with the present day experimental facilities, that will explore these predicted quantum vacuum resonances.
Role of porosity on the defect structure of nanostructured metal oxides analyzed by electrochemical and xray diffraction methods
Simone Mascotto, Vedran Vonk, Heshmat Noei
One convenient strategy to improve the ionic and electronic diffusion in transition metal oxides is nanostructuring.
In the case of nanoporous materials the charge transport properties result altered probably due to different effective charge of the defects sites near the material surface. Considering the high technological impact of porous oxides in electronic applications (dye sensitized solar cells, fuel cells), this proposal aims to study for the first time the effect of porosity on the atomic structure and charge transport of nanostructured metal oxides. To this purpose we apply electrochemical and x-ray diffraction methods on TiO2 with defined pore size and shapes, coated on substrates with dominant electronic (Pt) and ionic (YSZ) properties. In addition we want to combine both techniques in a single in situ experiment, which, if performed not only on laboratory scale but also at synchrotron sources like PETRA III, can catapult the planned project into a new, unexplored area of metal oxides structure-property relationship research.
Controlled nano- and micro-droplet generation using microfluidic liquid jet devices
Sebastian Bommel, Gerhard Grübel, Henry Chapman, Martin Trebbin
For nano- and microanalytical applications such as bioanalytics and nano-rheology the control of the sample volume is essential. In the last decade it has been shown that microfluidics is ideally suited for the manipulation and generation of defined volumes of diluted liquids, e.g. solution of single-particles or macromolecular crystals. In this project the development of smart microfluidic liquid jet devices for the production of nano- and micro-droplets is proposed. The integration of piezoelectric actuators in our established microfluidic jet devices enables us to achieve single-file monodisperse micro-droplets. By the integration of several actuators making multi-mode frequencies possible the generation of satellite droplets in the sub-μm regime can be triggered and influenced. Furthermore, multiple-gas focusing stages can be used for the generation of a nano-droplet spray. For the size-dependent separation of the single droplets field flow fractionation is used resulting in the generation of a uniform droplet stream. In cooperation with the Grübel and Chapman group at DESY the nano- and micro-droplets are used for pioneering research in terms of nano-rheology of anisotropic nanoparticles and the imaging of (single-)particles.