Wikidata: Q691851
ISNI: 000000010790385X
<script type="text/javascript">
<!--
document.write('<div id="oa_widget"></div>');
document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=corda_______::2c08b1350fe433cae8d9ba41a2e7b882&type=result"></script>');
-->
</script>
<script type="text/javascript">
<!--
document.write('<div id="oa_widget"></div>');
document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=corda_______::2c08b1350fe433cae8d9ba41a2e7b882&type=result"></script>');
-->
</script>
<script type="text/javascript">
<!--
document.write('<div id="oa_widget"></div>');
document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=corda_______::4559e25f6fecc486cf4fa9475566e2b9&type=result"></script>');
-->
</script>
<script type="text/javascript">
<!--
document.write('<div id="oa_widget"></div>');
document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=corda_______::4559e25f6fecc486cf4fa9475566e2b9&type=result"></script>');
-->
</script>
Tuberculosis (TB) is one of the most aberrant causes of global mortality and the molecular mechanisms of its pathogenesis are not well understood. The extrapulmonary dissemination of TB involves requires a crucial virulence factor designated as heparin-binding haemaglutinin adhesin (HBHA). HBHA is a 28 kDa dimeric protein localised at the surface of the Mycobacterium tuberculosis (MTB) that binds dextran sulphate, dermatan sulphate, glycosaminoglycans and heparan-sulphate proteoglycans thus mediating the adhesion with epithelial cells and to extracellular matrix components. Despite a crucial role in the dissemination of TB, a key relevance as strong diagnostic antigen and as therapeutic target, there is currently limited understanding of the structure and mechanism of action of HBHA. The ambitious aim of this proposal is to characterise at high-resolution the mechanisms of function of HBHA in different phases of the life cycle of MTB. To achieve this ambitious target, we will carry out an integrated investigation of solution-state and solid-state NMR nuclear magnetic resonance (NMR) to acquire high-resolution data on the interaction of HBHA with membranes of MTB. The NMR experiments will be complemented with biophysical studies and mutagenesis to accurately define the relationship between structure, dynamics and function of HBHA. Our preliminary data suggest that this ambitious project comes at the most opportune time as we now have tools, materials and knowledge to resolve this important goal for biochemistry and reveal the propeties of a crucial molecule for the mechanism of extrapulmonary dissemination of TB.
<script type="text/javascript">
<!--
document.write('<div id="oa_widget"></div>');
document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=corda__h2020::f866e9f67f2855888eb3c6ee5ab6f31a&type=result"></script>');
-->
</script>
<script type="text/javascript">
<!--
document.write('<div id="oa_widget"></div>');
document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=corda__h2020::f866e9f67f2855888eb3c6ee5ab6f31a&type=result"></script>');
-->
</script>
The holographic principle is believed to embody key fundamental features of any quantum gravity theory. It can be seen as a profound consequence of the intrinsic tension between the definition of quantum observables and the fact that in a theory of gravity it is impossible to define such observables in any finite volume due to the existence of Black Holes. The aim of this project is to push the boundaries of the holographic principle beyond AdS space, formulating a set of self-consistency requirements in dS, flat and inflationary backgrounds directly at the level of the sought-after holographic observables. If successful, this will allow us to understand the basic model independent principles at the basis of a quantum gravity theory and to check if a result of a calculation is consistent with unitarity and causality providing a paradigm shift in the search for consistent quantum gravity theories. The bottom-up perspective developed by HoloBoot will also be centred on phenomenological applications, ranging from classifying model-independent properties of consistent gravitational EFTs to understanding signatures of new particles during Inflation.
<script type="text/javascript">
<!--
document.write('<div id="oa_widget"></div>');
document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=corda_____he::9f93d32cac627ad9252ee5284b934d66&type=result"></script>');
-->
</script>
<script type="text/javascript">
<!--
document.write('<div id="oa_widget"></div>');
document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=corda_____he::9f93d32cac627ad9252ee5284b934d66&type=result"></script>');
-->
</script>
Gut Microbiota is a key actor for human health, driving many physiological and pathological processes, including immune system development and modulation. How this massive population of microorganisms, most of which are bacteria, establishes commensal, mutualistic or pathogenic interactions with the human host despite the vigilance of the immune system, is still obscure and requires an in-depth study. The story gets more intricate considering that gut is home for a myriad of Gram-negative bacteria whose outer membrane main constituent is the lipopolysaccharide (LPS). Due to its chemical structure, LPS is considered a potent elicitor of immune inflammatory reactions in mammals, being usually associated to perilous bacteria and detrimental outcomes for human health. Nevertheless, LPS also decorates the membrane of harmless and beneficial Gram-negatives of gut microbiota. How LPS is tolerated and remains (apparently) silent in the gut is a major unsolved question representing a frontier in our understanding of innate immunity. DEBUGGING-LPS project will contribute to answer this question, starting from the assumption that the chemistry of LPS is the real message taken from human host of the bacterial interaction, either beneficial or harmful. Strategically based on my expertise in organic chemistry, and integrating synthetic chemistry and cellular immunology studies, DEBUGGING-LPS will decrypt the 'chemical language' spoken by LPS in the gut. This project will deliver a clear picture of the chemistry at the basis of the difference between 'good' and 'bad' LPS, providing tools for the exploitation of the acquired knowledge to create novel therapeutics for resolving/mitigating immune disorders. DEBUGGING-LPS has been conceived to go beyond the state-of-the-art, breaking the dogma of LPS as an enemy, leaving space for a new vision of this glycomolecule: i.e. no longer as a toxic bacterial product rather as an immune signal vital for the proper functioning of our body.
<script type="text/javascript">
<!--
document.write('<div id="oa_widget"></div>');
document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=corda_____he::104e7132087a1b29058fdb9baccfa893&type=result"></script>');
-->
</script>
<script type="text/javascript">
<!--
document.write('<div id="oa_widget"></div>');
document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=corda_____he::104e7132087a1b29058fdb9baccfa893&type=result"></script>');
-->
</script>