306 Projects, page 1 of 62
Fluid dynamics is an effective description that applies to a variety of physical systems such as the quark-gluon plasma produced in heavy-ion collisions at RHIC and LHC. Recently, it has become of foremost importance to develop a hydrodynamic theory that incorporates the effects of statistical thermal fluctuations of the background. With such a framework at hand, it would be possible to analytically access many physical situations where statistical fluctuations are dominant such as in turbulent flows and, for example, around the putative critical point in the phase space of Quantum Chromodynamics (QCD) at finite temperature and finite baryon density. Another place where such considerations become relevant is in the physics of Quantum Chaos. Recent developments have shed new light into manifestations of many-body quantum chaos and have lead to the formulation of an effective theory for chaotic systems, albeit with a large number of degrees of freedom. Deviations from this limit seem to strongly indicate the necessity of including statistical fluctuations. Understanding these effects would help to classify the different universality classes of chaos to complete the survey of its manifestations. The research proposal “UniCHydro” addresses several strategic aspects mentioned above related to universal properties of fluid dynamics and quantum chaos. The Experienced Researcher is an expert on Schwinger-Keldysh effective field theory techniques which constitute the starting point for developing this research proposal. The stimulating environments of MIT and the University of Florence will allow then the Experienced Researcher to acquire the new set of skills in analyzing statistical fluctuations and new competencies in quantum chaos which will be fundamental to enhance its career prospects and to become a mature and independent scientist.
Kidney disorders represent a major global health issue and new tools are needed to expand disease modeling and therapeutic options. The identification of renal progenitors (RPC) opens a wide range of possibilities to support progress in several fields of nephrology. Indeed, RPC have become a key player in the pathogenesis of kidney disorders, and their study is increasing knowledge about the mechanisms of kidney response to injury. In this project we propose new lineage tracing models to identify and characterize mouse RPC system. We then will use these models to establish RPC role in progression or resolution of glomerular and tubular injury, and the mechanisms involved in these processes. Furthermore, the role of abnormal RPC function in the pathogenesis of renal cell carcinoma will be established. We will proceed to validate RPC as therapeutic targets to improve podocyte regeneration and disease regression. Lineage tracing of the murine RPC system from development to adult life and characterization of the RPC niche will be performed through observation of RPC at various stages of nephron formation during development as well as during kidney growth, homeostasis and aging. RPC isolation and culture from kidney tissue being limited due to their inaccessibility, the recent development of a method for culturing them specifically from urine finally opens the perspective of personalized medicine of the kidney and the development of patient-specific treatment strategies. In addition, patient-specific RPC can be useful for screening of new drug compounds, developing disease-modifying assays, as well as for evaluation of drug toxicity, with particular regard to nephrotoxicity. Finally, RPC represent potential tools and/or targets for therapeutic purposes and to promote innovative renal replacement strategies for kidney disorders.
Chronic pain, characterized by increased sensitivity to innocuous/mild stimuli (allodynia), afflicts 25% of the European adult population. Efficacy and/or safety of analgesic medicines is limited, and the treatment of chronic pain associated with inflammation, peripheral and central neuropathies and cancer remains unsatisfactory. Thus, identification of novel targets for better and safer analgesics is a major medical need. Transient receptor potential ankyrin 1 (TRPA1) channel, expressed by a subpopulation of primary sensory neurons (nociceptors), has been proposed as a major transducer of acute pain. We have, recently, identified that TRPA1 is expressed in Schwann cells that ensheath peripheral nerve fibres. In a prototypical model of neuropathic pain (sciatic nerve ligation in mice), we discovered that Schwann cell-TRPA1 exerts a hitherto unknown role that, via amplification of the oxidative stress message, sustains neuroinflammation and chronic pain (allodynia). Thus, Schwann cells, through their own repertoire of channels and enzymes orchestrate in the injured/inflamed tissue an autocrine/paracrine signalling pathway to sustain chronic pain. The purpose of the present project is to extend this observation to other models of inflammatory, neuropathic and cancer pain to identify a general paradigm based on Schwann cell/TRPA1/oxidative stress as the pathway that sustains chronic pain. We aim also at identifying in oligodendrocytes (the Schwann cells of the brain) whether the TRPA1/oxidative stress pathway sustains pain in the central nervous system. In mouse, rat and human Schwann cells/oligodendrocytes we aim at identifying biomarkers and combine them into biosignatures predictive of the susceptibility to the development of chronic pain. We anticipate that each molecular step that entails the TRPA1/oxidative stress pathway in Schwann cell lineages is an eligible target for discovering new effective and safer medicines for the treatment of chronic pain.
Acute kidney injury (AKI) is a global public health concern which results in 1.7 million deaths per year. If not lethal in the acute phase, AKI is considered reversible as suggested by recovery of renal function. However, even mild AKI episodes carry substantial risk of developing subsequent chronic kidney disease (CKD). The pathophysiological basis for this phenomenon remains unclear. Injury and death of tubular cells are recognized as the main factors in the pathogenesis of AKI and functional recovery from AKI was traditionally attributed to the regenerative capacity of tubular epithelial cells (TECs) which are believed to re-enter the cell cycle and repair the damage. Nevertheless, my preliminary data provide evidence that an endocycle-mediated response of remnant TECs may represent a critical mechanism of response to AKI. Endocycles are cell cycle variants consisting of G and S phases alone that repeatedly proceed without cytokinesis and its role in repair of mammalian tissues is mostly unknown and totally unexplored in the kidney. This proposal will be structured into 3 distinct objectives to address: 1. The physiologic relevance of endocycle for kidney function recovery after AKI 2. The role of endocycle in the progression of AKI to CKD; 3. The mechanism by which YAP1 drives endocycle and contributes to CKD development. To this end I will use lineage tracing techniques based on the FUCCI2aR reporter applied in different transgenic animal models of AKI, together with in vitro experiments in human primary cultures of renal tubular cells. Collectively, the outcomes of this proposal are expected to provide an entirely novel view of the kidney’s response to AKI, to further our understanding of the processes that drive CKD following AKI, as well as to describe for the first time endocycle as a critical response mechanism to tissue injury in the mammalian kidney.
One of the greatest challenges of the 21st century is to meet the world’s future food security and sustainability needs despite the rapid and large declines in suitable resources needed for the agricultural expansion required in the foreseeable future. As a result, interest in saline resources has escalated over the years but, notwithstanding great efforts from the scientific and breeding community, success in the development of salt tolerant crops remains elusive. For major breakthrough in crop breeding for salt tolerance, there is an urgent need to look at new options to find previously unexplored traits and mechanisms. With a multi-disciplinary approach and state-of-the-art biophysical and molecular techniques used in plant molecular biology, ion transport biology, halophyte ecophysiology and electrophysiology, the project will reveal the fine print of one of the most interesting mechanisms evolved by plants to deal with excess salts and thrive in these otherwise hostile environments. Given that dicotyledonous halophytes use sodium as a cheap osmoticum, the main objective of the project is to unravel the complementary morphological, physiological and anatomical characteristics that enable them to deal with cytotoxic sodium. The project will focus on four distinct halophytic species (facultative vs. obligate and with vs. without salt bladders): Atriplex nummularia, Chenopodium quinoa, Salicornia dolichostachya and Beta vulgaris ssp. marittima. By understanding how these different halophytes orchestrate efficient vacuolar Na sequestration with greater cytosolic K retention and bladder cell-based desalination, this project is expected to led the way to uncharted pathways to pinpoint key biological mechanisms that could improve tolerance in traditional salt sensitive crops. Public engagement activities and contact with the scientific and agricultural community will ensure a rapid transfer of knowledge and improve the likelihood of developing new salt tolerant crops.