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MPG

Max Planck Society
Country: Germany
755 Projects, page 1 of 151
  • Open Access mandate for Publications and Research data
    Funder: EC Project Code: 101054447
    Overall Budget: 2,171,250 EURFunder Contribution: 2,171,250 EUR
    Partners: MPG

    Eukaryotic messenger ribonucleoprotein (mRNP) particles are the functional entities that carry genetic information to the protein synthesizing machinery. These ribonucleoprotein complexes are dynamic and diverse, as highlighted by the copious number of proteins and transcripts identified in global proteomic and transcriptomic studies. However, little is known about the composition and architecture of individual mRNPs, and how changes in mRNP structure relate to their function or to dysfunction. The GOVERNA project will address this gap in knowledge by purifying specific mRNPs and delving into their molecular and structural arrangement. With our preliminary data serving as a springboard, the project combines genomic tagging engineered to maintain the most physiologically relevant conditions, biochemical methods developed to preserve the integrity of transient ribonucleoprotein assemblies, and mass spectrometry and cryo-electron microscopy to identify the composition and architecture of mRNPs. We will zoom-in on a set of paradigms in RNA biology that not only sample the breadth of mRNP diversity, but are also powerful model systems for linking structural information and biological function. We will investigate the molecular features in the three-dimensional organization of nuclear mRNPs from S. cerevisiae and of translationally repressed mRNPs in early developmental stages in D. melanogaster and X. laevis. For mRNPs undergoing active translation, we will investigate the transitions of human beta-globin mRNPs in the course of a surveillance process connected to disease. By studying these examples, we will glean fundamental insights into global principles governing the packaging of mRNPs and the remodeling of their three-dimensional features throughout a transcript’s life-cycle. The cumulative output will illuminate a central node of eukaryotic gene expression that is also particularly timely and relevant given recent developments in mRNA-based therapeutics.

  • Open Access mandate for Publications and Research data
    Funder: EC Project Code: 101025187
    Overall Budget: 264,669 EURFunder Contribution: 264,669 EUR
    Partners: MPG

    Over the last decades, we have established a standard cosmological paradigm by combining the information from complementary cosmological probes. However, many intriguing questions remain to be answered: the nature of dark energy, the driving mechanisms of the cosmic inflation, and masses of neutrinos. In this proposal, I will focus on the cosmological information content of the large-scale structure (LSS) of the Universe. Different physical processes leave their unique imprints on the clustering pattern of LSS at different scales, and N-point statistics act a bridge between the observables and the underlying physics. In the coming years, new large-volume galaxy surveys will probe the LSS of the Universe with exquisite detail. However, traditional analysis methods, based mostly on 2-point statistics alone, are not adequate for these new surveys and must urgently be revised to ensure their full potential. This proposal aims to maximise the information to be extracted from the upcoming surveys. With the Marie-Curie fellowship, I will carry out a consistent joint analysis of the 2- and 3-point statistics, and develop a complementary but simplified treatment of the N-point statistics. These tools will be applied to the new data to constrain the cosmological models, with special focus in understanding the properties of the primordial signatures and models beyond the standard cosmological paradigm. In the outgoing phase, I will work at Univesity of Florida (US) to benefit from the expertise in the leading algorithms to estimate higher-order statistics, their theoretical modelling, and knowledge about high-performance computing. In the incoming phase, I will work at the Max Planck Institute for Extraterrestrial Physics (Germany), I will delve into the data from the real surveys and understand potential systematic errors. With the help of the experts at MPE, the experience and techniques acquired in the US will be applied to the datasets to extract more precise information.

  • Open Access mandate for Publications
    Funder: EC Project Code: 707154
    Overall Budget: 171,461 EURFunder Contribution: 171,461 EUR
    Partners: MPG

    The FOF1-ATPase is a complex nanomotor that synthesizes nearly 90% of the ATP made during cellular respiration. It consists of two coupled rotary motors: an integral membrane complex driven by proton flow across lipid bilayers (FO) and an enzymatic complex that converts ADP and inorganic phosphate to ATP (F1). The rotational portion of these motors acts as a camshaft, inducing conformational changes that lead to ATP synthesis in the F1 motor’s three functional catalytic sites. The F1 motor can perform ATP synthesis in the absence of FO, and it can also work in reverse, hydrolyzing ATP to pump protons against an established gradient. Over the last 30 years many important aspects of this motor’s function have been elucidated by careful biochemical work and further understood by clever biophysical experiments. However, there is still not a complete, quantitative description of the whole thermodynamic cycle—one that fully describes the interactions between all three separate catalytic sites and accounts for the need to exchange ATP (found abundantly) for the relatively sparse ADP.

  • Open Access mandate for Publications and Research data
    Funder: EC Project Code: 101065466
    Funder Contribution: 189,687 EUR
    Partners: MPG

    PROteolysis TArgeting Chimera (PROTAC) is a new and attractive therapeutic approach that regulates a target protein by channeling it to the proteasome for degradation (an energy-demanding pathway). Concurrently, proteasomes also play a central role in generating the peptide repertoire for antigen presentation on the Human Leukocyte Antigen-I (HLA-I) molecules. A few years after PROTAC was invented, proteasomes were found to catalyze not only canonical peptide bond hydrolysis, but are also capable of “cut-and-paste” events, i.e. generating spliced peptides, which have been shown to be frequently presented n HLA-I immunopeptidomes. It is unclear how PROTAC-driven proteasome degradation modulates the spliced and non-spliced peptide repertoire derived from a targeted protein. Alterations in peptide variety and quantity produced by proteasome may lead to strong implications on the HLA-I immunopeptidome, and, hence, could result in immune implications. Therefore, using the key oncoprotein KRAS as a PROTAC’s target, this study intends to understand: (i) how PROTAC-driven KRAS degradation affects cellular pathways on a system-wide level; (ii) the impact of PROTAC on KRAS derived peptide repertoire generated by proteasomes; (iii) to what extent PROTAC enhances KRAS derived peptide presentation on HLA-I molecules. Through the combination of a multidisciplinary approach; molecular biology, biochemistry, proteomics, bioinformatics and cellular immunology, this study will provide a better fundamental understanding of the effect of PROTAC-KRAS on the cellular proteome, proteasome-derived peptide repertoire (spliced and non-spliced peptides) and HLA-I immunopeptidome landscape, thus, provide insights into the suitability of PROTAC-KRAS application as a therapeutic approach for anti-cancer therapies. Additionally, this project will deepen our understanding of the role of spliced peptides in the antigen processing and presentation pathway.

  • Open Access mandate for Publications
    Funder: EC Project Code: 896245
    Overall Budget: 205,353 EURFunder Contribution: 205,353 EUR
    Partners: MPG

    The structural anomalies of corpus callosum (CC) in patients are found highly-correlated with a wide range of disorders, e.g., epilepsy, autism, schizophrenia and mental retardation. However, it remains unclear about the causal contributions of CC-mediated functional changes to these disorders and exactly how the changes influence the local cortical circuitry. Lately, we have successfully combined fMRI with fiber optic mediated calcium recordings and optogenetics, i.e., multi-modal fMRI, to study the balance of excitation/inhibition in the barrel cortex in rats by pairing optogenetic corpus callosum activation with ascending thalamocortical activation. However, it remains challenging to maintain high sensitivity to the brain dynamic signal and better decipher CC-mediated unique cellular (neuron/astrocyte) or layer-specific contributions to the local cortical or global whole-brain fMRI signals. Therefore, the goal of this proposal is to optimize the multi-modal fMRI platform and to characterize the brain activity upon optogenetic callosal activation with higher spatial/temporal resolution using two cutting edge technologies, wireless amplified nuclear MR detector (WAND) and photonic crystal fiber (PCF). Previously, we have implanted a wireless RF coil into the rat body to achieve a high signal-to-noise ratio and spatial resolution for in vivo kidney imaging. The modified WAND will be incorporated into the multi-modal fMRI platform to achieve brain dynamic signal with enhanced sensitivity from the barrel cortex. Next, we will merge it with a novel PCF-based probe integrated calcium recording, optogenetic manipulation and fluid injection function. This proposal will merge the neuronal and astrocytic dynamic signals to the functional mapping, solve the challenges for CC study at multiple scales in the brain, enable novel applications of the multi-modal fMRI platform to better decipher the neuroglial interactions in normal and diseased animal models for future studies.