Partner 1

The Centre for Integrative Biology (CIBIO) of the University of Trento has been established only 3 years ago (data). It includes the Laboratory of Translational Genomics and is a Biomedicine Research Centre whose mission is to look for a synthesis between fundamental research in cell structure and function and translational biomedicine.

Unit P1.1

The Laboratory of Translational Genomics, headed by Alessandro Quattrone, is a mixed "wet/dry" molecular/systems biology lab with 15 members (1 PhD student, 8 first level postdocs, 6 experienced postdocs) whose expertise ranges from computational biology to biochemistry to molecular biology. The lab is fully equipped with state-of-the-art instrumentation, allowing us to perform all the experiments required. The basic science interests of the lab are on the sequence-dependent translational control of gene expression exerted by translation factors and RRM-type RNA binding proteins on motifs located in the 3' untranslated region of specific mRNAs. The techniques and the approaches developed by the lab are applied to the study of transcription/translation coupling and uncoupling in cell models, to the building of models of translation on structural basis, to the finding of alterations in sequence-dependent translational control in neural tumors (melanoma, glioma, neuroblastoma), to the finding of alterations in translational control in neurological diseases (Alzheimer disease, motor neuron diseases), to the development of translation-based drug discovery cell-based assays.

Alessandro Quattrone
Laboratory of Translational Genomics
Università degli Studi di Trento - CIBIO

Unit P1.2

The Laboratory of Molecular and Cellular Neurobiology, headed by Paolo Macchi at CIBIO, is interested in understanding the molecular mechanisms of RNA localization inneurons. The research is focused on the identification of proteins that bind to and transport the mRNAs into dendrites and deliver them to synapses. To study this question, combined techniques in molecular, cell and neurobiology with fluorescence and time-lapse video-microscopy to visualize protein and RNA movements in living cells have been developed in the lab. This multidisciplinary approach will help to unravel the mechanisms that regulate both RNA and RNA-binding proteins during localization. This knowledge will be also crucial for a better understanding of the pathogenesis of neurological diseases.

Paolo Macchi
Laboratory of Molecular and Cellular Neurobiology
Università degli Studi di Trento - CIBIO

Unit P 1.3

The Laboratory of Genomic Screening is led by Alessandro Provenzani, is at the moment composed of 4 members (2 post-doc and 2 PhD students) and 3 undergraduate students. The activity of the laboratory is aimed at exploiting the information derived from "omic" sciences to develop more rational drug screening pipelines. Several projects, focused towards the development of molecular assay to be used in the screening process, are currently running in the lab. Specific interest is devoted to unveil the role of an RNA binding protein (namely ELAVL1) in the etiology and progression of breast cancer.

Alessandro Provenzani
Laboratory of Genomic Screening
Università degli Studi di Trento – CIBIO

Partner 2

The Biophysics Institute (IBF) was established in May 2001 from the merging of five research centres of Italy's National Research Council (CNR). The Institute is based in Genoa and has four separate research divisions located in Milan, Pisa, Palermo and Trento. IBF has research links with academic and research institutions in over 20 European and non-European countries, as well as numerous well-established contacts with Italian research teams from universities and other organizations. IBF's research funding relies on both institutional sources and external financial support. In 2011 around 30 projects carried out in the Institute were funded either by the European Union or by specific research programmes run by the Italian Ministries and the local government. IBF's mission is to apply methodologies and techniques typical of the physical sciences to the study of the structure and functions of biological systems. Over the years, biophysics has firmly established itself as a fundamental discipline whose contributions have gone well beyond the mere application of physical techniques to the study of living systems. It plays a crucial role in the development of new methodologies and establishes ever closer links with other frontier areas of the biological and medical sciences (structure-function relations in biological molecules, molecular biology, bioenergetics, bioinformatics). This evolution has widened the range of skills required of the individual researcher and has increased the need for teams with diversified specialisations, who are able to tackle problems of ever increasing complexity using complementary approaches.

Unit 2.1

The IBF Unit of Trento (CNR-IBF/TN) is grouped around a main research focus dealing with biological membranes, macromolecular complexes and biomolecular imaging. In particular, the following research topics are faced and carried out in several biological models, from single molecules to living cells and organisms: 1) biophysics of pore forming proteins (bacterial toxins), 2) study of the superstructural organization of RNA and proteins in the polyribsomes, 3) photosensory biophysics of visual and unconventional opsin­based proteins, 4) development and design of molecular probes for fluorescence microscopy and molecular imaging. Expertizes range from physics to biology, through biophysics, physiology and molecular biology. A a joint CMM-BioSlnt (Biofunctional Surfaces and Interfaces Group) and CNR­IBF/TN laboratory is placed at Bruno Kessler Foundation composed of several areas: the biophysical and biochemical rooms, the cell and bacterial culture room, the molecular biology room, the optical microscopy room and Atomic Force Microscopy (AFM) room. Main available techniques are: optical spectroscopy (absorbance and fluorescence), fluorescence microscopy (white field and confocal), AFM instrument (Cypher, Asylum Research) for in liquid analyses (iDrive), infrared spectroscopy (FTIR), light scattering, column chromatography (HPLC), gel electrophoresis and blotting, oligopeptides synthesis. The main research stream of the scientist in charge for this project aims at the establishment of a new stream of research in the new multidisciplinary field of the superstructure and function of polyribosomes by means of nanoresolution imaging and high-throughput analysis of gene expression. In the past four years we have developed a great experience on polyribosome imaging and purification from cell cultures and fresh tissues in collaboration with in the Lab of Translational Genomics at CiBio and the Biofunctional Surfaces and Interfaces Group of the Bruno Kessler Foundation. The competences acquired concern most common molecular biology techniques (cloning, gene expression analyses (qPCR and Microarray), biochemical approaches (chromatography, electrophoresis, western blot), cellular biology (gene silencing, various functional assays) and imaging (Atomic Force Microscopy, Confocal Microscopy and STED Nanoscopy). Our aim is to address the superstructural organization of the most common and complex cytoplasmic machinery of eukaryotic cells as being related to the translational control con gene-expression. By using different nanoresolution imaging approaches such as Atomic Force Microscopy, Stimulated Emission Depletion Nanoscopy and cryo-Electron Microscopy we aim at revealing the fundamental structural and functional details to discover new investigation paths in studying the molecular determinants of translation. The deep and well established collaboration on this topic between CNR-IBF/TN, FBK and CiBio leads in less than three years in more than five poster presentation at national and high profile international congresses and two selected oral presentation. Moreover, relevant international collaboration has been established with the Division of Structural Biology (STRUBI), Nuffield Department of Clinical Medicine (NDM) - University of Oxford and the Unit for Nanophysics, of the Italian Institute of Technology (Genova).

Gabriella Viero

Partner 3

Fondazione Bruno Kessler (FBK) is a private no-profit organization established by the government of the Autonomous Province of Trento (IT) in 1962 (formerly known as Istituto Trentino di Cultura, ITC) and conducts research in the areas of Materials and Microsystems, Information Technology, Mathematics, Italo-Germanic Historical Studies and Religious Sciences. FBK­irst, the scientific hub of FBK, was founded in 1976 and, for nearly three decades, it has been conducting research in the areas of Information Technologies, Microsystems, and Physical Chemistry of Surfaces and Interfaces carried out in its ICT Center for Information Technology and the CMM Center for Materials and Microsystems. Today, FBK-irst is an internationally recognized research body with a budget of 20 million euro, and employs approximately 240 researchers who directly supervise over thirty PhD students from the University of Trento. FBK-irst takes an active interest in the needs of the Province of Trento while collaborating with internationally recognized universities and research institutions, industry, and public and private laboratories in Italy and abroad.

Unit 3.1

The Materials and Microsystems Center (CMM) is composed of 125 senior and young researchers, post docs, PhD students and technicians and focuses research on key areas of materials and microsystems with the aim of pushing innovation through scientific excellence, maximizing practical impact and networked innovation. The CMM collaborates with industries, universities, and public and private laboratories in Italy and abroad for research projects and R&D activities. The CMM contributes to the micro and nanotechnology fields with its state of the art expertise in nano-on-micro approaches with applications in biomedicine, energy and environment, and sensors development. Briefly the following activities are represented: silicon quantum structures for photonics, plasmonics and organic solar cells; THz radiation sensors; gas sensors; nanostructured thin films, nanocomposites, nanolayers, nanoparticles for delivery and imaging; surface modifications for biosensing, materials and devices for molecular diagnostics. Simulation of processes of biological interest and of innovative materials is also undertaken.

Cecilia Pederzolli
Materials and Microsystems Center (CMM)
Fondazione Bruno Kessler

Partner 4

The Department of Biomedical Sciences of the University of Padova is committed to excellence in research in the Biomedical Sciences and to training of Scientists through its Graduate School and Courses of Doctorate. Specific areas of research are Signal Transduction, Mitochondria! Pathophysiology, Muscle and Heart Pathophysiology, Host-Pathogen Interactions, Cancer Biology, Neurobiology and Neuropathology. These research themes reflect the history of the three Departments that merged into the present one and the fact that the Department hosts the Padova Section of the CNR Institute of Neuroscience. The Laboratory is fully equipped with state-of-the-art instrumentation for Cell Biology, Biochemistry, Molecular Biology and Electrophysiology .

Unit 4.1

The Host-Pathogen Interaction (HPI) laboratory headed by Cesare Montecucco is focused on three research lines which are complementary to each other in terms of scientific content and in terms of techniques used. Mechanism of blockade of neurotransmitter release by tetanus and botulinum neurotoxins. Mechanism of the degeneration of the motor axon terminals induced by snake presynaptic PLA2 neurotoxins (SPANs) and by the spider a-latrotoxins. Mechanism of regeneration of the motor axon terminals of mice injected with SPANs or a-latrotoxins with major focussing on the role of the peripheral Schwann cells and of the innervated muscle fibres. In these activities, the research group has already obtained major results and will invest its major effort on line 3. The Host-Pathogen Laboratory has studied a variety of human diseases caused by toxins or virulence factors including diphtheria, tetanus, botulism, anthrax and the gastric diseases associated to Helicobacter pylori. At the present time the research activity of the laboratory is focused on neurotoxins and myotoxins and follows three lines of research: a) the study of the molecular mechanisms underlying the degeneration of motor neurons axons terminals induced by some animal neurotoxins, b) the study of the mechanism and cellular actions that govern the following complete regeneration of the neuromuscular junction with particular attention on the role of the peripheral Schwann cells and of the innervated muscle cells; c) the mechanism of binding and entry of the tetanus and botulinum neurotoxins into nerve terminals. For these studies the laboratory has developed methods of molecular and cellular biology, of imaging using fluorescence microscopy and classical and molecular electrophysiology.

Cesare Montecucco
Host-Pathogen Interaction (HPI) laboratory
Università degli Studi di Padova

Partner 5

Euan MacDonald Centre for Motor Neurone Disease Research and Centre for Integrative Physiology at the University of Edinburgh. The Membership of these two centres provides access to a range of state-of-the-art core facilities for morphology and molecular biology and also provides access to a range of leading clinical and scientific expertise. These centres are equipped with core facilities required to process tissue for in vitro and in vivo experiments detailed in this project. The centres benefit from extensive collaborations with other biologists and clinicians at leading universities around the world (e.g. Cologne University, Columbia University and Oxford University).

Unit 5.1

Thomas Gillingwater's (THG) laboratory investigates mechanisms underlying neurodegeneration and neuroprotection, with a particular focus on models of motor neuron disease and events occurring in axonal and synaptic compartments of neurons. His laboratory routinely combines high-resolution morphological analyses (e.g. transmission electron microscopy and confocal microscopy) with genomic and proteomic technologies in mouse models. Recent research highlights include studies revealing numerous genetic influences on degeneration and regeneration of synapses and axons after injury (e.g. Nature Neurosci, 2001; Brain, 2005 & 2006; Hum Mol Genet, 2006 & 2011; Mol Cell Proteomics, 2007; Genome Biol, 2008; Current Biol, 2012; PLoS Genet 2012), studies revealing morphological and genetic factors regulating the pathogenesis of spinal muscular atrophy (e.g. Am J Hum Genet, 2004; Hum Mol Genet, 2008, 2010, 2011 & 2014; PLoS Genet, 2009; J Clin Invest, 2014; Mol Ther, 2015), studies examining mechanisms underlying development of synaptic connectivity in vivo and in vitro (e.g. J Neurosci, 2006, 2008 & 2014; Nature Commun, 2011 & 2015), and studies demonstrating the contribution of axons and synapses to pathogenesis in mouse models of lysosomal storage disorders and Huntington's disease (e.g. Eur J Neurosci 2004; J Neuropathol Exp Neurol, 2008 & 2011; Hum Mol Genet, 2009). Since 2004, THG has attracted >£5m in external grant funding from sources including the Wellcome Trust, Medical Research Scotland and the BBSRC. THG is Editor-in-Chief at Journal of Anatomy.