ERC FUNDED PROJECTS

"To date no experiment has investigated ion-molecule reactions at temperatures significantly below about 20 K, for two reasons: (i) Cooling the translational and internal degrees of freedom of ions and molecules is extremely challenging. (ii) Even very weak stray electric fields accelerate the ions. A potential difference of only 1 mV across the reaction volume imparts a kinetic energy of 1 meV to ions, which corresponds to a temperature of about 12 K. Quantum mechanical effects arising from the translational and the frozen or hindered rotational motion of the reactants in the intermolecular potential are only expected to be significant below 20 K and have therefore not been observed yet in ion-molecule reactions, even for reactions involving the lightest ions and molecules. This proposal aims at developing a new experimental method to study ion-molecule reactions at temperatures down to 100 mK and to study ion-molecule reactions involving light species, with particular emphasis placed on the observation and quantification of quantum effects in low-temperature ion-molecule chemistry. To reach this goal, we will study the ion-molecule reactions within the orbit of a highly excited Rydberg electron, which will shield the reaction from stray fields without affecting its outcome. To reach very low collision energies, we will use a merged-beam approach relying on a surface-electrode Rydberg-Stark deflector. In the preparatory phase of this proposal, we have carried out a proof-of-principle measurement of the H2+ + H2 -> H3+ + H reaction below 1 K using a simplified version of the ""ideal"" instrument and demonstrated the feasibility of our method. We now plan to exploit the full potential of our new approach and study important ion-molecule reactions in a temperature range thought until now to be experimentally inaccessible."

2 130 088 €

Start date: 2017-06-01, End date: 2022-05-31

The purpose of this proposal is to establish new fundamental insight of the reactivity and thereby the catalytic activity of oxides, nitrides, phosphides and sulfides (O-, N-, P-, S- ides) in the Cluster-Nanoparticle transition regime. We will use this insight to develop new catalysts through an interactive loop involving DFT simulations, synthesis, characterization and activity testing. The overarching objective is to make new catalysts that are efficient for production of solar fuels and chemicals to facilitate the implementation of sustainable energy, e.g. electrochemical hydrogen production and reduction of CO2 and N2 through both electrochemical and thermally activated processes. Recent research has identified why there is a lack of significant progress in developing new more active catalysts. Chemical scaling-relations exist among the intermediates, making it difficult to find a reaction pathway, which provides a flat potential energy landscape - a necessity for making the reaction proceed without large losses. My hypothesis is that going away from the conventional size regime, > 2 nm, one may break such chemical scaling-relations. Non-scalable behavior means that adding an atom results in a completely different reactivity. This drastic change could be even further enhanced if the added atom is a different element than the recipient particle, providing new freedom to control the reaction pathway. The methodology will be based on setting up a specifically optimized instrument for synthesizing such mass-selected clusters/nanoparticles. Thus far, researchers have barely explored this size regime. Only a limited amount of studies has been devoted to inorganic entities of oxides and sulfides; nitrides and phosphides are completely unexplored. We will employ atomic level simulations, synthesis, characterization, and subsequently test for specific reactions. This interdisciplinary loop will result in new breakthroughs in the area of catalyst material discovery.

2 500 000 €

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

Cooperation is essential for the functioning of the economy and society. Thus, with inappropriate mechanisms to harness self-interest by aligning it with the common good, the outcome of social and economic interaction can be bleak and even catastrophic. Recent advances in computer technology lead to radical innovation in market design and trading strategies. This creates both, new challenges and exciting opportunities for “engineering cooperation”. This project uses the economic engineering approach (as advocated by Alvin Roth) to address some of the most pressing cooperation problems of modern markets and societies. I propose three work packages, each using innovative experimental methods and (behavioral) game theory in order to address a specific challenge: The first one studies the design of electronic reputation mechanisms that promote cooperation in the digital world. Previous research has shown that mechanisms to promote trust on the Internet are flawed. Yet, there is little empirical and normative guidance on how to repair these systems, and engineer better ones. The second studies the design of mechanisms that avoid arms races for speed in real-time financial and electricity market trading. Traders use algorithmic sniping strategies, even when they are collectively wasteful and seriously threatening market liquidity and stability. Yet, little is known about the robust properties of alternative market designs to eliminate sniping. The third one studies how to design modern markets that align with ethical considerations. People sometimes have a distaste for certain kinds of modern transactions, such as reciprocal kidney exchange and buying pollution rights. Yet, little is known about the underlying nature and robustness of this distaste. My project will generate important knowledge to improve the functioning of modern markets, and at the same time open new horizons in the sciences of cooperation and of “behavioral economic engineering”.

1 155 104 €

Start date: 2018-03-01, End date: 2023-02-28

Epigenetic inheritance is the transmission of information, generally in the form of DNA methylation or post-translational modifications on histones that regulate the availability of underlying genetic information for transcription. RNA itself feeds back to contribute to histone modification. Sequence accessibility is both a matter of folding the chromatin fibre to alter access to recognition motifs, and the local concentration of factors needed for efficient transcriptional initiation, elongation, termination or mRNA stability. In heterochromatin we find a subset of regulatory factors in carefully balanced concentrations that are maintained in part by the segregation of active and inactive domains. Histone H3 K9 methylation is key to this compartmentation. C. elegans provides an ideal system in which to study chromatin-based gene repression. We have demonstrated that histone H3 K9 methylation is the essential signal for the sequestration of heterochromatin at the nuclear envelope in C. elegans. The recognition of H3K9me1/2/3 by an inner nuclear envelope-bound chromodomain protein, CEC-4, actively sequesters heterochromatin in embryos, and contributes redundantly in adult tissues. Epiherigans has the ambitious goal to determine definitively what targets H3K9 methylation, and identify its physiological roles. We will examine how this mark contributes to the epigenetic recognition of repeat vs non-repeat sequence, and mediates a stress-induced response to oxidative damage. We will examine the link between these and the spatial clustering of heterochromatic domains. Epiherigans will develop an integrated approach to identify in vivo the factors that distinguish repeats from non-repeats, self from non-self within genomes and will examine how H3K9me contributes to a persistent ROS or DNA damage stress response. It represents a crucial step towards understanding of how our genomes use heterochromatin to modulate, stabilize and transmit chromatin organization.

2 500 000 €

Start date: 2017-06-01, End date: 2022-05-31

Solid-state NMR has recently made a significant impact on structural biology by providing atomic-resolution structures of several, previously uncharacterized proteins. A particularly relevant example is the Amyloid-beta (Aβ) peptide linked to Alzheimer’s disease where we determined the atomic-resolution structure of Aβ(1-42) and of the Osaka mutant of Aβ(1-40). A spectral resolution revolution is now in reach that will enable solid-state NMR to address new frontiers in structural biology. The applications mentioned above are based on 13C-detected spectroscopy. Proton-detected experiments, although clearly more sensitive thanks to the high gyromagnetic ratio of 1H, have found few applications so far, due to the poor resolution of 1H spectra caused by the 1H-1H dipolar interaction. The proton resolution can be enhanced by employing faster rotation of the sample, i.e. higher MAS (magic-angle spinning) frequencies. Presently accessible MAS frequencies are already faster than the ones of any other man-made object. A significant improvement is still attainable in our view. Increasing the MAS frequency to 200-250 kHz will improve the spectral quality to favorably compare with solution NMR for larger proteins, including fully protonated systems. In addition, the amount of sample required is reduced by almost two orders of magnitude, to approx. 100 μg, compared to the about 10 mg needed in 13C-detected experiments. This removes an important bottleneck in sample-preparation. The resolution and sensitivity gain will allow the structural characterization of e.g. disease-relevant amyloids or membrane proteins with higher precision. Moreover, this approach will enable the investigation of complex systems, which presently elude structural characterization. The resolution revolution brought about by fast spinning shall thus represent a breakthrough since it will open new horizons for solving urgent biological and medical questions.

2 173 375 €

Start date: 2017-10-01, End date: 2022-09-30

Recent breakthroughs in the field of genome editing provide a genuine opportunity to establish innovative approaches to repair DNA mutations to replace, engineer or regenerate malfunctioning cells in vitro or in vivo. However, most of the recently developed technologies introduce double-strand DNA breaks at a target locus as the first step to gene correction. These breaks are subsequently repaired by one of the cell intrinsic DNA repair pathways, typically inducing an abundance of insertions and deletions (indels). Ideally, for many applications genome editing should, however, be efficient and specific, without the introduction of indels. Site-specific recombinases (SSRs) allow precise genome editing without triggering endogenous DNA repair pathways and possess the unique ability to fulfill both cleavage and immediate resealing of the processed DNA in vivo. However, customizing the DNA binding specificity of SSRs is not straightforward. With this project, we propose to solve this shortcoming. We have already demonstrated that by applying substrate-linked directed evolution, SSRs can be generated that specifically recognize therapeutic targets. The objective of this project is the development of a universal genome editing platform that allows flexible, efficient and safe gene corrections in cells of any origin without triggering cell intrinsic DNA repair. GenSurge aims to: i) sequence an unprecedented, comprehensive compendium of evolved SSRs to understand the directed molecular evolution process at nucleotide resolution; ii) integrate the knowledge obtained in i) to develop a unique SSR-based approach to correct genomic inversions; iii) develop a universal SSR-based strategy that allows flawless, precise and safe genome editing to correct any gene defect in human, animal or plant cells. The successful implementation of this project will deliver a comprehensive, safe and efficient platform from which genome surgery-based cure strategies can be initiated.

2 380 425 €

Start date: 2018-01-01, End date: 2022-12-31

Ultra-short light pulses have become invaluable in time-resolved studies in chemistry and physics. But many important processes are initiated by collisions. While lasers have revolutionized experiments using light pulses, experimentally proven concepts for producing ultra-short pulses of neutral matter are still in their infancy. Hence, our ability to control when a collision occurs is still extremely limited. Recently, we have reported bunch-compression photolysis, the first demonstrated method for producing ultra-short pulses of neutral matter. Here, photolysis of jet-cooled hydrogen iodide is carried out with femto-second laser pulses whose frequency bandwidth has been spatially ordered. Thus, fast H-atom photoproducts overtake slow ones, producing an ultra-short pulse.The central objective of this project is to develop bunch-compression photolysis as a tool for ultrafast timing experiments involving collisions of ultrashort pulses of H-atoms at synchronously photo-excited solid surfaces. Bunch-compression photolysis allows collisions at a surface to be synchronized with photoexcitation on the ps time scale, opening up new ways to study the dynamics of collisions at selectively photo-excited surfaces that have not yet relaxed. Studies on collision dynamics involving excitons produced in 2D semiconductors is one exciting direction for this work. Experiments on synchronized H atom collisions with vibrationally excited surfaces prepared by infrared photoexcitation is another - this enables kinetics experiments with surface site-specificity as well as the direct observation of reaction intermediates. The work and ideas presented here show how to overcome the most challenging barrier to a new class of time-resolved dynamics experiments, opening new frontiers in the study of surface chemistry, where we will begin to understand how selected degrees of freedom of the solid influence collision dynamics and reaction rates.

2 499 356 €

Start date: 2017-10-01, End date: 2022-09-30

Banking crises are thought to be recurrent phenomena that generally come on the heels of strong credit growth. Their damaging real effects have generated a broad agreement among academics and policymakers that financial regulation needs to tighten and to obtain a macroprudential dimension that aims to lessen the negative externalities from the financial to the macro real sector. Among the main ingredients that are often mentioned to have played a role in the explosive growth of credit in the run-up to the latest financial crisis are the financial innovations by financial institutions, in particular loan securitization, the boom in mortgage lending and prices of real estate, the lack of information about prospective borrowers, and the high leverage (and corresponding low capital ratios) of financial institutions. Yet, despite the singling out of these ingredients by policymakers, decisive empirical evidence about their role and relevancy is lacking. However, given the magnitude and complexity of the global banking system and the lack of encompassing micro-level data, it is currently impossible to confidently study the impact of all ingredients jointly. This project therefore analyses pertinent settings where we can empirically identify the correspondence between the aforementioned individual ingredients and the credit granting by financial institutions. The objective of the project is to advance identification and estimation of the impact of each respective factor on loan growth by combining the appropriate methodology with an exceptional set of micro-level datasets. When missing in the literature a theoretical framework will be provided. The project further aims to assess how potential combinations of these ingredients may have interacted in spurring credit growth. While the identification of the impact of each ingredient on credit growth is paramount, the individual setting of the studied datasets and employed methodologies will ensure maximum external validity.

2 103 440 €

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

Reversible epigenetic modifications regulate gene expression to define cell fate and response to environmental stimuli. Gene expression tuning by DNA and chromatin modifications is well studied, yet the effect of RNA modifications on gene expression is only starting to be revealed. More than a hundred chemical modifications decorate RNAs, mainly non-coding ones, expanding their nucleotide vocabulary and mediating their diverse functions. Several modifications were globally mapped in mRNA. Only two, N6-methyladenosine (m6A) and N1-methyladenosine (m1A) exhibit a distinct topology alluding to a functional role. We pioneered the identification of m6A that is located preferentially in distinct transcript landmarks, mostly around stop codons and mediates transcript localization, splicing, decay and translation. We now identified m1A which decorates thousands of genes mainly in the start codon vicinity, upstream to the first splice site. Our preliminary results indicate that m1A dynamically responds to environmental stimuli and plays a central role in translation regulation. The regulation and functions of m1A are still terra incognita. Our objectives are to identify m1A writers and erasers, elucidate m1A readers and the mechanisms whereby m1A dictates downstream outcomes, particularly translation regulation. We will study m1A functions in response to physiologic stimuli and stress conditions in cells and animal models by manipulation of the m1A deposition machinery. As epigenetic marks operate in a context-dependent concerted way we will map m1A marks concomitantly with m6A to decipher their interplay in regulating gene expression via a putative “epigenetic RNA code”. The data obtained from parallel mapping of m1A and m6A at a single nucleotide and a single transcript resolution, will expose the interplay between these two mRNA modifications in the context of multilayer epigenetics. The study of m1A circuits may identify targets amenable to therapeutic manipulations.

2 457 500 €

Start date: 2017-07-01, End date: 2022-06-30

How is political accountability and firm performance in an autocracy affected by media? This project will analyse how economic and political outcomes in China are affected by social and traditional media. It will also use media content to measure factors that are otherwise difficult to observe, such as political networks and the trade-off between political and economic goals in Chinese firms. An explosion of social media use in China has produced an information shock to society and its leaders, also supplying a data shock to researchers, which is magnified by the digitization of traditional media content, and coupled with new methods for analysing this type of data, originating from the in big data and machine-learning literatures. As a result, a large set of previously unanswerable questions are now open for research. In Qin, Strömberg and Wu (2016) we document this information shock, using a data set of over 13 billion social media posts from Sina Weibo (the Chinese equivalent of Twitter). We show that millions of posts concern sensitive topics such as organized protests and explicit accusations of top leaders of corruption. Traditional media is silent on these issues. We argue that the likely reason for the lighter censoring of social media is that the central government finds the information useful for monitoring officials, firms, and citizen unrest. In this project, I will analyze the effect of this information shock on protests and strikes, the sales of counterfeit and substandard medicines, the promotion of local leaders, and coverage of censored events in traditional media. Together with a set of collaborator, I will study the effects of social media using the staggered introduction of Sina Weibo across geographic regions. I will also study the content, entry and exit of general-interest newspapers that are all controlled by different politicians. This is to investigate the trade-off between political and economic goals and political connections.

1 716 970 €

Start date: 2018-01-01, End date: 2022-12-31