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Goethe University Frankfurt

Goethe University Frankfurt

15 Projects, page 1 of 3
  • Funder: UKRI Project Code: EP/X016455/1
    Funder Contribution: 454,684 GBP

    Unravelling the complex structures encountered in macromolecular assemblies from biology to advanced materials is paramount to functional understanding. For biomolecules (such as proteins and DNA) high-resolution structure determination techniques (such as crystallography and cryo-electron microscopy) have been indispensable for structure-function studies. However, the emergence of powerful deep learning based high-accuracy structure prediction tools has sent shock waves through the structural biology community and heralds a new era for structural studies where the routine generation of laborious experimental high-resolution structures could be replaced with computational predictions. These predictions can form the basis to design structure-function studies upon experimental validation and refinement. The (bio)physical tool called electron paramagnetic resonance (EPR) spectroscopy is ideally suited to complement predicted structures. EPR detects the magnetism arising from the "spin", a quantum mechanical property of unpaired electrons. Electrons are contained in all matter and are commonly paired, quenching their magnetism. However, unpaired electrons such as free radicals underpin many important biological processes like photosynthesis, ageing, and respiration. Using EPR, distances in-between such spins can be determined on the nanometre (one billionth of a metre) scale. Over the past 20 years, these distance measurements have developed into an important and powerful method for investigating the nanoworld of complex (bio)molecules. Molecular biology and chemistry allow labelling specific sites in biomolecules by selectively introducing spins that can then be used as molecular "beacons". Introducing two such beacons allows measurement of the distance between them. With this approach structures of proteins and other macromolecules are successfully mapped, validated and refined. In this project, deep learning-based structure prediction and modelling tools will be combined with state-of-the-art EPR techniques (including orthogonal copper(II)-SLIM labelling for low-concentration RIDME and unbiased deep learning-based data processing), to validate and refine the structural model of a protein evading experimental high-resolution structure determination. Based on purely computational, high-accuracy structure prediction it is possible to generate informative EPR constructs of the protein where the molecular beacons will report on features critical for structure and structural transitions during function. The distances between different beacons will be used to feed back into the structural model for validation and refinement. Interaction with binding partners during function leads to structural changes which alter distance and relative orientation of beacons. Determination of these alterations with EPR will show the potential of this approach and demonstrate its opportunities for wide-reaching impact. Artificial intelligence is increasingly affecting many aspects of our everyday lives. Similarly, deep learning revolutionises the way structural studies are performed. This project showcases the benefits of the marriage between deep learning-based structure prediction and structural refinement and validation using EPR. The approach and workflows established here are fully transferable, widening the application scope of EPR for structure-function studies, especially regarding challenging systems currently beyond reach (owing to their size, complexity, flexibility, membrane environment or achievable amount or concentration). Here, the approach is applied to a bacterial surface protein of unknown structure implicated in rheumatic heart disease, and proposed experiments have the potential to uncover the structural mechanism of the host-pathogen interaction. Only with a greater knowledge of the biological nanoworld will it be possible to pinpoint the molecular causes of diseases, and aid in developing prevention and treatment strategies.

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  • Funder: UKRI Project Code: NE/I00646X/2
    Funder Contribution: 167,874 GBP

    Summary for General Public: The aim of Integrated Ocean Drilling Programme (IODP) expedition 318, to the Wilkes Land margin of Antarctica, is to decipher the long-term climate and environmental Antarctica: from the pre-glacial Greenhouse world, through the history of multiple growth and collapse of the East Antarctic Ice Sheet (EAIS) and related sea-level changes. The expedition used the specialist drill ship, the Joides Resolution, to recover deep sea sediments. There has been a continuous process of erosion of rocks and soils from the Antarctic continent and deposition of these sediments in the receptive environment of the deep ocean, where layer upon layer of sediment can be laid down in undisturbed succession. These sediments are a repository of information on past environmental and oceanographic changes. Abundant organic molecular fossils (biomarkers) and organic walled microfossils were found in the sediment cores recovered by the IODP 318 expedition. Certain compounds (especially lipids) are quite resistant to decay, so after the producer organisms expire, the biomarkers are preserved in sediments. These biomarkers can be extracted, measured and used to reconstruct changes in parameters such ocean and land temperature over thousands to millions of years; allowing us to quantitatively reconstruct past changes in climate and environments. In expedition IODP 318 these fossils are most abundant is cores dating from the Greenhouse period before ice-sheets were present on Antarctica (the Early Eocene Period, 48 to 55 million years before the present). The presence of the biomarker fossils and organic walled microfossils offers a unique opportunity to study the pre-glacial Antarctic during the critical Early Eocene period, which was characterised by high atmospheric CO2 and mean global temperatures that reached a long-term maximum. Moreover, superimposed on this long-term warmth were a series of relatively rapid (less than a few tens of thousands of years), extreme warm events known as hyperthermals. We will combine state-of-the-art molecular organic biomarker techniques and palynological (organic-walled microfossils) analyses to reconstruct, at high-resolution, changes in land and sea temperatures, atmospheric CO2, carbon cycle changes, terrestrial evaporation/precipitation, marine productivity and salinity. Study of this Greenhouse period and the hyperthermal events is crucial because, since industrialisation, atmospheric concentrations of CO2 have grown to be higher now than at any time in the last 2 million years (Myr). Over the same period, concentrations of other greenhouse gasses (GHGs: methane, nitrous oxides etc) have increased markedly due to human activity. If emissions continue unabated, by 2035 we will have effectively doubled the amount of carbon dioxide in the atmosphere (550 ppm CO2e), compared to the preindustrial period. In other words, atmospherically speaking, we are rapidly heading back towards the Eocene period during which the planet was warmer, planetary ice volumes were much lower and sea-levels much higher than present. We request funding which will allow the PI, James Bendle to co-ordinate project team and lead in the multi-proxy, molecular biomarker analyses. If UK science is to take competitive advantage of the IODP 318 moratorium period (which expires in June 2011), then funding from the April 2010 NERC UK-IODP call is critical to facilitate our proposed analyses and outcomes.

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  • Funder: UKRI Project Code: EP/L025736/1
    Funder Contribution: 496,658 GBP

    Superconductivity is a phenomena that has the potential to transform society. For example, the lossless transport of electricity through wires has the ability to make tremendous savings in our electrical distribution infrastructure. The unique properties of superconductors enable several other key technologies, such as the generation of large, ultra stable magnetic fields needed for magnetic resonance imaging in healthcare. The unique properties of superconducting Josephson junctions are perhaps the most promising route towards the development of a quantum computer which could revolutionize our digital economy. Although many applications of superconductors are already in the marketplace there is still enormous potential. To realise this we need to gain a better understanding of the phenomena of superconductivity, in particular its microscopic origin in so-called unconventional high temperature superconductors which have been discovered in the last 25 years. Although there has been much progress towards the goal of developing a microscopic theory of unconventional superconductivity the answer has still not been found. A highly promising, relatively recent, theory to explain these effect relies on physics of the highly quantum mechanically entangled state of matter which exists close to a quantum critical point, where an order/disorder phase transition is tuned to absolute zero by some external parameter such as pressure. In this proposal we plan to study in detail the effect of quantum criticality on the superconductivity in several different candidate systems. These materials encompass all the major families of superconductors which have been discovered in the last 25 years (cupates, organics, heavy fermions, iron-pnictides) can all be tuned towards an quantum critical point with external pressure. Unfortunately, superconductivity itself prevents almost all established methods used to study quantum criticality. One way round this problem is to apply a large external magnetic field to quench the superconductivity. However, this may also have the effect of modifying the quantum critical behaviour of interest. Fortunately, the magnetic penetration depth provides a sensitive and unique probe of the underlying normal state electronic structure with zero applied magnetic field and at very low temperature. Our proposal seeks to measure the absolute penetration depth in a pressure cell for the first time. This will provide unique information which will guide theories of how (or if) quantum criticality causes high temperature superconductivity.

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  • Funder: UKRI Project Code: EP/W007436/1
    Funder Contribution: 61,854 GBP

    Waves propagating in the atmosphere and ocean need to be represented in the numerical models used for weather and climate prediction in order to capture the strong impact they have on the atmospheric and oceanic circulation, on the state of the sea surface, and on the transport of pollutants. This cannot be achieved directly, however, because the typical wavelengths are much shorter than the grid scales of even the highest resolution numerical models. A reduced mathematical model that averages over the short wavelengths offers a solution but poses a major computational challenge. It describes the distribution of wave-action density in an extended position-wavenumber phase space; hence, it requires solving a partial differential equation in up to 6 space-like dimensions. This is beyond the reach of traditional discretisation methods. This project aims at demonstrating the feasibility of an alternative approach, based on a dynamical low-rank approximation of the wave-action density. This approach expands the wave action as a sum of products of functions of a few variables, constructed on-the-fly to project the dynamics onto the space of low-rank functions while minimising an error. The project will formulate an algorithm based on low-rank approximation and splitting, implement two versions that use different combinations of grid-based and spectral discretisations, and test them against a ray-tracing algorithm (specifically designed to capture the dynamics of a few wavepackets) and against direct numerical simulations of the underlying fluid equations. The formulation and implementation will emphasise parallelisation and efficiency on supercomputers, with testing carried out on ARCHER2. The project primarily targets the modelling of internal waves, with a focus on the representation of their scattering by turbulence and of nonlinear wave-wave interactions. Applications to ocean surface waves will also be considered.

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  • Funder: UKRI Project Code: AH/X004899/1
    Funder Contribution: 189,175 GBP

    While much scholarship has examined processes of invention of tradition in the recent past, less work has been done on what this study refers to as the "re-invention of tradition"- processes by which continuous forms of ritual tradition take on new meanings over the course of multiple generations. The project takes up this topic through a study of the longue durée history of the Carnival tradition. Looking at the case of the Rhineland and examining Carnival through the lens of the history of emotions, the project excavates the radical re-invention of the tradition's perceived meaning from the sixteenth to the nineteenth century and explores the routes through which its meaning changed. While promoting a new line of inquiry into the re-invention of tradition, the project will also use a history of Carnival to examine changing attitudes towards communal celebration as an emotional practice. In doing so, it will help fill a persistent gap in the history of emotions around studies of "positive" emotions. While studies of Carnival have typically looked at shorter periods of its history to shed light on politics and social orders, a longue durée purview reveals the profound re-invention of its meaning over generations. Throughout the Late Middle Ages, Carnival was broadly understood as a representation of the Kingdom of Hell defined by worldly pleasure-seeking, Schadenfreude, and violent displays. The Carnival jester appeared as the torturer of Christ, with the medieval tradition representing the fallen state of man to be overcome on Ash Wednesday when Carnival ends and the fasting of Lent begins. Much evidence, however, suggests that Carnival had taken on very new meanings by the nineteenth century. While the Carnival jester had been transformed into the "happy victor," celebrants described Carnival joy not as representing the fallen state of man, but rather as a positive, social, healing, and community-forming emotion which compensated individuals for the burdens of industrial production. Modern Carnival simultaneously represented a site of debate over exuberant joy, the proper means of its pursuit, and the relationship of the emotion to social class, politics, morality, and public order. The project will address a series of questions: What made Carnival so re-inventable and how did this contribute to its survival? Did these changes occur through intergenerational slippage and forgetting or intentional efforts to revise its meaning? When, exactly, did these changes occur and what do they tell us about evolving ideas about communal celebration as an emotional practice? When did Carnival celebrants begin to describe the emotions of Carnival as healing and when did they reject Schadenfreude as an appropriate Carnival emotion? The emotional history of the tradition, finally, evokes questions about theories of modernity as defined by growing demands for emotional control. Does an emotional history of Carnival support or problematize this theory? The project findings will particularly be useful for public bodies involved in recent efforts to "safeguard" forms of intangible cultural heritage. While Carnival traditions have been included in ICH lists, this project calls for greater attention to how meanings of such forms of heritage have changed. Failure to understand these histories of transformation magnifies the risk of closing off routes of re-invention in the name of preservation. The project findings will be disseminated through academic and popular channels, including through a special museum exhibition, monograph, and journal articles. In the framework of the project, I will also co-organize an international workshop on the history of Carnival with partners at the University of Frankfurt. The workshop will bridge across divisions in the study of Carnival based on national context and time period and will result in an edited volume which explores the possibilities opened up by breaking through these barriers.

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