ERC FUNDED PROJECTS

For many years, the ubiquitin-26S proteasome degradation pathway was considered the primary route for proteasomal degradation. However, it is now becoming clear that proteins can also be targeted for degradation by a ubiquitin-independent mechanism mediated by the core 20S proteasome itself. Although initially believed to be limited to rare exceptions, degradation by the 20S proteasome is now understood to have a wide range of substrates, many of which are key regulatory proteins. Despite its importance, little is known about the mechanisms that control 20S proteasomal degradation, unlike the extensive knowledge acquired over the years concerning degradation by the 26S proteasome. Our overall aim is to reveal the multiple regulatory levels that coordinate the 20S proteasome degradation route. To achieve this goal we will carry out a comprehensive research program characterizing three distinct levels of 20S proteasome regulation: Intra-molecular regulation- Revealing the intrinsic molecular switch that activates the latent 20S proteasome. Inter-molecular regulation- Identifying novel proteins that bind the 20S proteasome to regulate its activity and characterizing their mechanism of function. Cellular regulatory networks- Unraveling the cellular cues and multiple pathways that influence 20S proteasome activity using a novel systematic and unbiased screening approach. Our experimental strategy involves the combination of biochemical approaches with native mass spectrometry, cross-linking and fluorescence measurements, complemented by cell biology analyses and high-throughput screening. Such a multidisciplinary approach, integrating in vitro and in vivo findings, will likely provide the much needed knowledge on the 20S proteasome degradation route. When completed, we anticipate that this work will be part of a new paradigm – no longer perceiving the 20S proteasome mediated degradation as a simple and passive event but rather a tightly regulated and coordinated process.

1 500 000 €

Start date: 2015-04-01, End date: 2020-03-31

The suite of graphene’s unique properties and applications can be enormously enhanced by its functionalization. As non-covalently functionalized graphenes do not target all graphene’s properties and may suffer from limited stability, covalent functionalization represents a promising way for controlling graphene’s properties. To date, only a few well-defined graphene derivatives have been introduced. Among them, fluorographene (FG) stands out as a prominent member because of its easy synthesis and high stability. Being a perfluorinated hydrocarbon, FG was believed to be as unreactive as the two-dimensional counterpart perfluoropolyethylene (Teflon®). However, our recent experiments showed that FG is not chemically inert and can be used as a viable precursor for synthesizing graphene derivatives. This surprising behavior indicates that common textbook grade knowledge cannot blindly be applied to the chemistry of 2D materials. Further, there might be specific rules behind the chemistry of 2D materials, forming a new chemical discipline we tentatively call 2D chemistry. The main aim of the project is to explore, identify and apply the rules of 2D chemistry starting from FG. Using the knowledge gained of 2D chemistry, we will attempt to control the chemistry of various 2D materials aimed at preparing stable graphene derivatives with designed properties, e.g., 1-3 eV band gap, fluorescent properties, sustainable magnetic ordering and dispersability in polar media. The new graphene derivatives will be applied in sensing, imaging, magnetic delivery and catalysis and new emerging applications arising from the synergistic phenomena are expected. We envisage that new applications will be opened up that benefit from the 2D scaffold and tailored properties of the synthesized derivatives. The derivatives will be used for the synthesis of 3D hybrid materials by covalent linking of the 2D sheets joined with other organic and inorganic molecules, nanomaterials or biomacromolecules.

1 831 103 €

Start date: 2016-06-01, End date: 2022-05-31

"Two-dimensional (2D) nanosheets, which possess a high degree of anisotropy with nanoscale thickness and infinite length in other dimensions, hold enormous promise as a novel class of ultrathin 2D nanomaterials with various unique functionalities and properties, and exhibit great potential in energy storage and conversion systems that are substantially different from their respective 3D bulk forms. Here I propose a strategy for the synthesis and processing of various 2D nanosheets across a broad range of inorganic, organic and polymeric materials with molecular-level or thin thickness through both the top-down exfoliation of layered materials and the bottom-up assembly of available molecular building blocks. Further, I aim to develop the synthesis of various 2D-nanosheet based composite materials with thickness of less than 100 nm and the assembly of 2D nanosheets into novel hierarchal superstrucutures (like aerogels, spheres, porous particles, nanotubes, multi-layer films). The structural features of these 2D nanomaterials will be controllably tailored by both the used layered precursors and processing methodologies. The consequence is that I will apply and combine defined functional components as well as assembly protocols to create novel 2D nanomaterials for specific purposes in energy storage and conversion systems. Their unique characters will include the good electrical conductivity, excellent mechanical flexibility, high surface area, high chemical stability, fast electron transport and ion diffusion etc. Applications will be mainly demonstrated for the construction of lithium ion batteries (anode and cathode), supercapacitors (symmetric and asymmetric) and fuel cells. As the key achievements, I expect to establish the delineation of reliable structure-property relationships and improved device performance of 2D nanomaterials."

1 500 000 €

Start date: 2012-09-01, End date: 2017-08-31

I propose to investigate the nanometer scale organization of delicate 2-dimensional molecular materials using nanoscale vibrational spectroscopy. 2D structures are of great scientific and technological importance, for example as novel materials (graphene, MoS2, WS2, etc.), and in the form of biological membranes and synthetic 2D-polymers. Powerful methods for their analysis and imaging with molecular selectivity and sufficient spatial resolution, however, are lacking. Tip-enhanced Raman spectroscopy (TERS) allows label-free spectroscopic identification of molecular species, with ≈10 nm spatial resolution, and with single molecule sensitivity for strong Raman scatterers. So far, however, TERS is not being carried out in liquids, which is the natural environment for membranes, and its application to poor Raman scatterers such as components of 2D polymers, lipids, or other membrane compounds (proteins, sugars) is difficult. TERS has the potential to overcome the restrictions of other optical/spectroscopic methods to study 2D materials, namely (i) insufficient spatial resolution of diffraction-limited optical methods; (ii) the need for labelling for all methods relying on fluorescence; and (iii) the inability of some methods to work in liquids. I propose to address a number of scientific questions associated with the spatial organization, and the occurrence of defects in sensitive 2D molecular materials. The success of these studies will also rely critically on technical innovations of TERS that notably address the problem of energy dissipation. This will for the first time allow its application to study of complex, delicate 2D molecular systems without photochemical damage.

2 311 696 €

Start date: 2017-09-01, End date: 2022-08-31