• OA Publications Mandate: Yes close
• 2017 close

Chirality is a fundamental property of life, making chiral sensing and analysis crucial to numerous scientific subfields of biology, chemistry, and medicine, and to the pharmaceutical, chemical, cosmetic, and food industries, constituting a market of 10s of billion €, and growing. Despite the tremendous importance of chiral sensing, its application remains very limited, as chiroptical signals are typically very weak, preventing important biological and medical applications. Recently, the project-coordinating FORTH team has introduced a new form of Chiral-Cavity-based Polarimetry (CCP) for chiral sensing, which has three groundbreaking advantages compared to commercial instruments: (a) The chiroptical signals are enhanced by the number of cavity passes (typically ~1000); (b) otherwise limiting birefringent backgrounds are suppressed; (c) rapid signal reversals give absolute polarimetry measurements, not requiring sample removal for a null-sample measurement. Together, these advantages allow improvement in chiral detection sensitivity by 3-6 orders of magnitude (depending on instrument complexity and price). ULTRACHIRAL aims to revolutionize existing applications of chiral sensing, but also to instigate important new domains which require sensitivities beyond current limits, including: (1) measuring protein structure in-situ, in solution, at surfaces, and within cells and membranes, thus realizing the “holy-grail” of proteomics; (2) coupling to high performance liquid chromatography (HPLC) for chiral identification of the components of complex mixtures, creating new standards for the pharmaceutical and chemical analysis industries; (3) chiral analysis of human bodily fluids as a diagnostic tool in medicine; (4) measurement of single-molecule chirality, by adapting CCP to microresonators, which have already demonstrated single-molecule detection; and (5) real-time chiral monitoring of terpene emissions from individual trees and forests, as a probe of forest ecology.

The objective of PROOFY is to develop and commercialize an innovative cloud based web-application for copyright and authorship protection for individual and corporate users. Traditional protection solutions are costly and bureaucratic processes relying on legacy centralized monopolistic institutions (notaries, collecting societies). PROOFY is tailored for creators and marketers of original content, enabling safe deposit and management of original work, being extremely easy (1-step procedure), fast (3min), inexpensive (€15/author/year) and entirely online. PROOFY revolutionizes IP protection being the only solution to ensure data integrity, certification of genuineness and authorship, with a fully automatic uploading process and secure storage services. Having successfully penetrated the Italian market (2,000 B2C users in 2017), we will secure our European position and introduce PROOFY to global markets (US and Asian). The PROOFY B2C component has been tested, validated and demonstrated both technically and commercially. We are now expanding the B2B component, and are planning to perform pilot tests in operational scenarios, for which partnerships and agreements are already in place. During the Phase 1 we will perform the technical and commercial assessment of PROOFY (design, functionalities, scale-up, security, market demands), so as to become the leading provider of Online Copyright Protection Services in EU and to penetrate the US and Asian markets with the most efficient solution. We will also develop a detailed Business and Financial Plan to analyse the economic viability of PROOFY. The successful implementation of this project will raise EU’s worldwide rank in copyright protection, and will stimulate job creations in the Creative Industry domain, which is the largest employment sector for young people and contributes to over 3% of EU’s GDP.

MULTIDRONE aims to develop an innovative, intelligent, multi-drone platform for media production to cover outdoor events, which are typically held over wide areas (at stadium/city level). The 4-10 drone team, to be managed by the production director and crew, will have: a) increased decisional autonomy, by minimizing production crew load and interventions and b) improved robustness, security and safety mechanisms (e.g., embedded flight regulation compliance, enhanced crowd avoidance, autonomous emergency landing, communications security), enabling it to carry out its mission even against adverse conditions or crew inaction and to handle emergencies. Such robustness is particularly important, as the drone team has to operate close to crowds and may face an unexpected course of events and/or environmental hazards. Therefore, it must be contextually aware and adaptive with improved perception of crowds, individual people and other hazards. As this multi-actor system will be heterogeneous, consisting of multiple drones and the production crew, serious human-in-the-loop issues will be addressed to avoid operator overload, with the goal of maximizing shooting creativity and productivity, whilst minimizing production costs. Overall, MULTIDRONE will boost research on multiple-actor systems by proposing novel multiple-actor functionalities and performance metrics. Furthermore, the overall multidrone system will be built to serve identified end user needs. Specifically, innovative, safe and fast multidrone audiovisual shooting will provide a novel multidrone cinematographic shooting genre and new media production techniques that will have a large impact on the financially important EU broadcasting/media industry. It will boost production creativity by allowing the creation of rich/novel media output formats, improving event coverage, adapting to event dynamics and offering rapid reaction speed to unexpected events.

Generating Hematopoietic Stem Cells (HSCs) by Transcription Factor (TF) overexpression is of great interest in the stem cell field and promises considerable therapeutic potential. Among the systems described so far only one study, using murine B cells, has led to the generation of transplantable induced HSCs (iHSCs), although at exceedingly low efficiencies and using combinations between 6 and 8 TFs. We propose here a new approach to generate iHSCs based on the use of newly identified highly plastic “elite” type cells for reprogramming by the Yamanaka factors into induced pluripotent stem cells, generated by the transient exposure of B cells to C/EBPα. Hypothesizing that microRNAs could potentiate the effect of TFs in HSC reprogramming we will also analyze the effects of microRNA overexpression. For this we will first analyze HSCs and different hematopoietic progenitors to identify differentially expressed microRNAs. Different combinations of selected microRNAs will be cloned into inducible retroviral vectors together with hematopoietic TFs and used to infect “elite” CEBPα-primed B cells to screen for the induction, in vitro and in vivo, of iHSCs. The use of colony assays, cell surface marker and transcriptomic analyses of the resulting cells, as well as transplantation into irradiated mice, will enable us to identify microRNAs and TFs combinations that induce HSC reprogramming. The heterogeneity of iHSCs will then be tested by single cell expression analysis using RNA-seq. This project will provide new insights into the reprogramming of HSCs, the clinically most important type of adult stem cells, with potential medical applications. The proposed action will benefit the applicant’s career through acquisition of scientific maturity and independence.

Cell biology is in the midst of a remarkable “resolution revolution” in which the invention of new optical microscope techniques is allowing visualisation of the dynamics of intra-cellular structures at unprecedented spatial and temporal resolution. We are requesting a Lattice Light Sheet Microscope (LLSM) as developed by Eric Betzig (Janelia) - recipient of the 2014 Nobel Prize for his earlier work on super-resolution microscopy - and a dedicated microscope technician. The LLSM enables simultaneous illumination of the entire field of view with an ultrathin sheet of excitation light permitting imaging at hundreds of planes per second with high axial resolution (~230-nm xy and ~370-nm z), negligible out-of-focus background and a dramatic reduction in photobleaching/toxicity/damage. The LLSM thus opens up a completely new horizon, enabling long-term interrogation of the mechanisms of cell biological machines, inside live cells. Our aim is to make this technology available to Warwick’s expanding cell and developmental biological community - nucleated by four Wellcome Investigators (McAinsh, Straube, Balasubramanian & Cross) based in the Centre for Mechanochemical Cell Biology. We will also establish a visitor programme - inspired by the advanced imaging centre at Janelia - to make this technology accessible to the wider community.

Non-Alcoholic Fatty Liver Disease (NAFLD), including its more pathologic consequence, non-alcoholic steatohepatitis (NASH), is believed to be the most common chronic liver disease worldwide, affecting between 6 to 37% of the population. NAFLD is a so called ‘silent killer’, as clinical symptoms only surface at late stages of the disease, when it is no longer treatable: untreated, NAFLD/NASH can lead to cirrhosis and hepatocellular carcinoma, culminating in liver failure. Currently the best method of diagnosing and staging the disease is liver biopsy, a costly, invasive and somewhat risky procedure, not to mention unfit for routine assessment. Besides, no therapeutic consensus exists for NAFLD/NASH treatment. mtFOIE GRAS (Foie Gras being French for "fat liver") proposes to address the pressing need for non-invasive, accurate, rapid assessment of NAFLD/NASH stages, before and after intervention, through the development of biomarkers and innovative tools to follow mitochondrial (mt) dysfunction, a central mediator of fatty liver disease pathogenesis. This promising R&D strategy will also bring new knowledge about the disease mechanisms and improved understanding of the pathogenic process and disease drivers. To that end, mtFOIE GRAS envisages a training-through-work plan that brings together an intersectoral, multidisciplinary team of researchers and technicians experts in their fields, from basic to translational research, clinical practice, technology commercialization and public advocacy. Together with several PhD students, the team will share expertises and work synergistically along the value creation chain to address the unmet medical need of more informative NAFLD assessment. In the process, mtFOIE GRAS will endow the involved staff with excellent scientific knowledge and transferable skills while building and strengthening intersectoral cooperation among partners, thus contributing to EU RD&I excellence.