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LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN

LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN

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61 Projects, page 1 of 13
  • Funder: WT Project Code: 220450
    Funder Contribution: 300,000 GBP

    Unconventional myosins of class I can directly associate with membranes, thereby providing a dynamic link between the actin cytoskeleton and the plasma membrane or intracellular organelles. Immune cell-specific myosin 1F and myosin 1G (MYO1F and MYO1G respectively) have roles in immune cell migration and regulation of membrane tension. Studies show both motors are upregulated in microglia during neuroinflammation. To uncover the temporal regulation of these motors, a number of biophysical assays will be employed, such as in vitro motility assays, optical trap experiments and stopped-flow spectroscopy. The molecular interactions of MYO1G that determine cellular function will be explored using a combination of proteomics and cell biological assays to identify the motors’ interacting partners and elucidate its spatial regulation in vivo. The effects of two distinct phosphorylation sites on motor domain activity of MYO1G will be explored with mutations to mimic the non- and phosphorylated states. Protein crystallography studies of MYO1F and MYO1G will enable the design of small molecule inhibitors using structure-based in silico screening, with the ultimate goal to treat neuroinflammation in humans. Taken together these approaches will elucidate the cellular and physiological role of these motors and uncover the potential use of MYO1F and MYO1G as therapeutic agents. Myosin is a cytoskeletal motor that uses metabolic energy stored in ATP to do mechanical work. In the cell, myosin members of the class I family are vital for membrane dynamics and cellular trafficking. Two isoforms of myosin are found specifically in immune cells, and have roles in immune cell migration and phagocytosis. I aim to understand the molecular basis of the spatial and temporal regulation of immune cell-specific myosins. I will employ a combination of proteomics and cellular analyses to identify the interacting partners of these motors. I will also use biophysical and biochemical techniques, such as optical trap experiments and stopped-flow spectroscopy, to investigate the impact of post-translational modifications on the regulation of these motors. These studies will help to explain how dysregulation of immune-specific myosins can give rise to neuroinflammation, a common feature of neurodegenerative disease, and can be used to design potential new therapies.

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  • Funder: WT Project Code: 226782
    Funder Contribution: 5,037,110 GBP

    Repetitive negative thought (RNT, worry, rumination) influences the onset and maintenance of anxiety and depression. Reducing RNT is an established active therapeutic ingredient. Although cognitive-behavioural therapy (CBT) targeting RNT is effective, the mechanisms underpinning treatment effects are unknown. Our key goals are to delineate the active therapeutic components and associated mechanisms-of-action of CBT targeting RNT, via experimental manipulation of treatment components within internet-delivered RNT-focused CBT and assessment of mediators in a large-scale factorial trial for individuals with elevated RNT. Combining components in a factorial experiment is more efficient for sample size and resource than conducting separate experiments and better tests the main effects and interactions of each factor than dismantling designs. Hypothesized mechanisms include (i) shifting from overgeneral abstract to specific thinking; (ii) breaking out of RNT-as-a-habit; (iii) replacing self-criticism with self-compassion; (iv) improved present-moment focus; (v) increased patient understanding of difficulties. People with Lived Experience will shape research questions and design: they will guide prioritising which mechanisms-to-study and they will co-design adaptations to existing interventions to better manipulate these mechanisms. This novel project will test these hypotheses experimentally, leading to more potent, economical, and accessible treatments for RNT available via an online platform to transform early intervention.

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  • Funder: NWO Project Code: 236-20-006
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  • Funder: UKRI Project Code: AH/P004415/1
    Funder Contribution: 197,893 GBP

    Many of the predictions of modern theoretical physics are extremely difficult to test. For example, Hawking's famous prediction that black holes radiate at a characteristic temperature. Since the temperature of `Hawking radiation' is very low, it is not (even in principle) detectable via observational astronomy. Furthermore, is is unlikely that we will ever be able to construct black holes here on earth. The lack of an in principle means for direct experimental testing of predictions such as Hawking radiation pose a challenge to conventional scientific methodologies. This challenge is taken up by techniques of `analogue simulation' wherein an accessible `source' system is used to simulate phenomena that are difficult or impossible to test directly within a `target' system. Analogue simulation in modern physics comes in two forms depending upon the type of source and target system: `quantum simulation' and `analogue gravity simulation'. In quantum simulation both source and target systems are typically within the domain of finite dimensional quantum theory. A simple example is where an array of ions (i.e. charged atoms) is controlled via magnetic fields such that they collectively simulate a ferromagnetic material (such as an iron bar magnet). Quantum simulations are potentially very powerful tools for gaining new insights into quantum systems that are hard to manipulate, for example relativistic quantum systems, nano-materials and quantum optical systems. In analogue gravity simulations, condensed matter systems, like fluids, are typically used to simulate gravitational systems, such as black holes or early universe cosmology. Analogue gravity simulations are potentially very powerful tools for gaining new insights into phenomena that are deemed impossible to test directly, such as Hawking radiation. This is a project in the philosophy of science within which we will evaluate the methodological, epistemological and metaphysical foundations of analogue simulation with the goal of providing analytic tools of direct use to scientists, philosophers of science, and science funding decision makers. We answer questions such as: What kind of evidence can analogue simulations provide?; What do analogue simulations have in common with computer simulations and experiments?; What is the scientific and economic value of analogue simulation? We propose that analogue simulation can be understood as a form of `Ersatz' experimentation, involving the `programming' of a physical system such that it can be used to `simulate' another physical system. In general terms, evidence gained from experiments on a particular system is only of real value to the extent to which we have justification for generalising it to a class of relevantly similar `target' systems. Such justificatory arguments are called `external validation' of an experiment. One of the key ideas explored in this project is conditions for external validation of analogue simulations. For example, we aim to examine the conditions in which the analogue simulation of Hawking radiation via condensed matter systems can be externally validated: i.e. when we can genuinely learn about black holes by doing experiments on the analogues.

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  • Funder: UKRI Project Code: AH/K008226/1
    Funder Contribution: 163,147 GBP

    From the South Asian Tsunami to the Haitian Earthquake, the last decade has witnessed a significant rise in the number of catastrophes experienced worldwide. These have highlighted the challenges and vulnerabilities faced by communities in the face of environmental hazards, inspiring sustained reflection on global responsibilities for prevention and aid. This project seeks to position such events in historical perspective as part of a much broader array of post-World War II crises and catastrophes - both social and environmental, chronic and acute - which have had disproportionate effects on the world's poorest communities, many of which are still grappling with the legacies of western colonialism. Departing from conventional methods of studying disasters, which tend to focus on North American and European examples, the project compares how a wide range of global catastrophes are portrayed in postcolonial literature and film. It argues that, taken together, these texts have much to reveal about how we think about disaster, providing new insights into vulnerability reduction that respond to local cultural contexts and to global processes that can heighten as well as mitigate risk. The project is situated in relation to the growing body of disaster representations produced in recent years by writers and filmmakers as diverse as Tahmima Anam, Dionne Brand, Kamau Brathwaite, James George, Tareque Masud, Raoul Peck, Kamila Shamsie, and Indra Sinha. These depict the everyday human consequences of catastrophes and their deep-lying causes, and require critics to focus as much on past and present experiences of real-world disasters as on future apocalyptic scenarios (such as those presented in The Road or The Day After Tomorrow). The perspectives generated by creative texts are especially valuable for disaster risk reduction when read alongside social science-based approaches. This is because researchers across numerous academic fields are now identifying a clear need to humanize and add cultural and historical depth to our understanding of disasters' social and environmental effects, and to look at how creative narratives and aesthetic forms shape different interpretations of catastrophes. The project will establish the extent to which postcolonial texts challenge, reject, or reconfigure key disaster studies concepts such as resilience, risk, adaption, sustainability, and vulnerability. At the same time, it will explore how disaster studies insights can help frame and inform textual readings of specific disasters. It will contribute to Care for the Future's core aim by providing historicised analyses of how aesthetic works can help us think through the tensions between continuity and change in the wake of real-world catastrophes. The primary output will be an academic research monograph and related articles focusing on the following case studies: the Israeli-Palestinian Conflict; Pacific Nuclearisation; the Bhola Cyclone and the Bangladesh Liberation War; the Bhopal Gas Disaster; the Rwandan Genocide; the Montserrat Volcano Eruptions; and the Haitian Earthquake. The project also includes a number of collaborative and exchange activities that will create links between literary scholars and disaster studies specialists from across multiple disciplines (especially anthropology, geography, history, political ecology, and sociology), and will demonstrate research applications to cross-sector stakeholders such as government, private sector, civil society, and third sector representatives. In particular, it seeks to impact on non-academic policy and practice by showing how humanities-based perspectives can help critique and contribute to disaster management and sustainability planning. The project will also engage the public through a series of commemorative activities in 2014 in conjunction with writers, critics, and charity representatives, a website, and a short film produced in collaboration with an independent filmmaker.

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