ERC FUNDED PROJECTS

Glycans, or oligosaccharides, are ubiquitous in biological systems. Because they decorate the surface of cells, they play a key role in virtually all cellular recognition processes and are implicated in almost every major disease. Despite their importance, the characterization of glycan primary structure lags far behind that of proteins and DNA because of their intrinsic isomeric complexity. The isomeric nature of the monosaccharide building blocks, the stereochemistry of the glycosidic bond, the possibility of multiple attachment points, and the occurrence of isomeric branched structures all make glycans difficult to analyze. Although mass spectrometry (MS) is one of the most sensitive approaches for glycan analysis, it has difficulty to distinguish all these various types of isomerisms. Ion mobility spectrometry (IMS) combined with MS has demonstrated some ability to identify glycan anomers and regioisomers, but cannot easily distinguish isomeric disaccharides, for example. We have recently demonstrated that cryogenic infrared spectroscopy provides unique vibrational fingerprints of glycans that distinguishes all the various types of isomerism. When combined with simultaneous measurements of mass and ion mobility, these fingerprints can be tabulated in a database and used to identify a given glycan from a mixture. However, adding a spectroscopic dimension to ion mobility and mass measurements requires additional time, which hampers it use as an analytical tool. To use spectroscopic data for real-world glycan analysis, one must multiplex the measurement process and record the vibrational spectrum of many species simultaneously. This project involves designing and constructing an instrument that combines state-of-the-art ion mobility separation, cryogenic ion spectroscopy, and time-of-flight mass spectrometry to perform high throughput analysis of glycan primary structure. The success of this project would represent a tremendous breakthrough for glycoscience.

2 499 801 €

Start date: 2018-09-01, End date: 2023-08-31

"The project will examine the impact of the system of penality developed in the Soviet gulag on the ethnic identification and political radicalisation of prisoners in the Soviet Union and the communist successor states of Europe today. It is informed by the proposition that prisons are sites of ethnic identity construction but that the processes involved vary within and between states. In the project, the focus is on the extent to which particular ""prison-styles"" affect the social relationships, self-identification and political association of ethnic minority prisoners. After the collapse of the Soviet Union, the communist successor states all set about reforming their prison systems to bring them into line with international and European norms. However, all to a lesser or greater extent still have legacies of the system gestated in the Soviet Gulag and exported to East-Central-Europe after WWII. These may include the internal organisation of penal space, a collectivist approach to prisoner management, penal labour and, as in Russian case, a geographical distribution of the penal estate that results in prisoners being sent excessively long distances to serve their sentences. It is the how these legacies, interacting with other forces (including official and popular discourses, formal policy and individual life-histories) transform, confirm, and suppress the ethnic identification of prisoners that the project seeks to excavate. It will use a mixed method approach to answer research questions, including interviews with ex-prisoners and prisoners' families, the use of archival and documentary sources and social media. The research will use case studies to analyze the experiences of ethnic minority prisoners over time and through space. These provisionally will be Chechens, Tartars, Ukrainians, Estonians, migrant Uzbek and Tadjik workers and Roma and the country case studies are the Russian Federation, Georgia and Romania."

2 494 685 €

Start date: 2018-11-01, End date: 2023-10-31

In this proposal, we introduce two new families of probes for live-cell super-resolution microscopy. The first class comprises small-molecule fluorescent sensors for detecting short-lived, small signaling molecules and active enzymes with single-molecule resolution. The spatiotemporal confinement of biological reactive molecules has been hypothesized to regulate various pathological and physiological processes, but the lack of tools to observe directly these microdomains of biochemical activity has precluded the investigation of these mechanisms. The ability to detect small signaling agents and active enzymes with nanometric resolution in intact live specimens will allow us to study the role of compartmentalization in intracellular signaling at an unprecedented resolution. Our studies will focus on detecting elusive reactive oxygen and nitrogen species directly at their sites of endogenous production. We will also investigate the subcellular distribution of protease activity, focusing on its role in non-apoptotic signaling. The second class of probes encompasses a palette of fluorescent dyes that switch continuously between dark and emissive forms. This dynamic equilibrium will enable the localization of single molecules in a densely labeled field without the need to apply toxic light for photoactivation. Based on a novel switching mechanism, we will prepare dyes of various emission wavelengths that blink in a controlled way. These dyes will allow us to perform, for the first time, super-resolution, multicolor, time-lapse imaging of live specimens over long time. Initial studies will focus on tracking a transcription factor that migrates from the endoplasmic reticulum to the nucleus to initiate a cellular stress response upon protein misfolding. These studies will provide spatiotemporal details of this important translocation, which takes more than one hour to occur and its observation at the single-molecule level is intractable with current super-resolution methods

1 498 125 €

Start date: 2019-10-01, End date: 2024-09-30

In reimagining the world’s energy future, while researchers are seeking alternative ways to produce energy, our current dependence on fossil fuels requires us to capture and store the CO2 to prevent reaching unacceptable CO2 levels in the atmosphere. In this scenario, recycling CO2 by converting it into useful chemicals, such as fuels for transportation, represents an important research area as it will eventually lead to independence from fossil fuels and petroleum. While much progress has been made, this emerging field is challenged by huge technical and scientific questions. The intrinsic thermodynamic stability of the CO2 molecule, combined with slow multi-electron transfer kinetics, makes its reduction exceedingly energetically demanding. Hy-Cat aims to develop novel material platforms to investigate different chemical paths that promote electrochemical CO2 reduction and direct product selectivity. We will synthesize hybrid materials comprising atomically defined CO2 sorbents and nanocrystalline CO2 catalysts intimately bound in a single integrated system. Three different classes of hybrids, each characterized by one specific absorption/pre-activation mechanism, will allow to investigate the effect of each mechanism on the catalyst activity. A key component of the research will be to develop synthetic schemes to access these multifunctional systems with an unprecedented level of control across multiple lengthscales. This control and the intrinsic tunability of the chosen building blocks will allow us to methodically compare structure and activity, so to determine the design principles upon which better catalysts can be made. We will argue that this understanding is required to remove the main bottlenecks towards efficient and selective catalysts to convert CO2 into useful products, such hydrocarbons. Hy-Cat is highly multidisciplinary and its scientific outcome will positively impact several other research fields in chemistry, materials science and engineering.

1 420 648 €

Start date: 2017-01-01, End date: 2021-12-31