The technology platforms
Selected projects
The execution of the winning projects entailed the development of 7 technology platforms, each with its specific objective.
BIOLOGICAL AND MOLECULAR CHARACTERIZATION OF CANCER STEM CELLS
Principal Investigator: Ileana Zucchi
Technology Platform: Genetics
Lead research organization : Consiglio Nazionale delle Ricerche (National Research Council)
Registered Office: Milan
Research conducted in: Milan
Award: €3.3 million
The overall objective of this project is the creation of human cancer model systems that permit to validate new emerging concepts in the biology of tumors, today seen as abnormal tissues that originate from and are sustained by transformed stem cells (SCs). The study of various pre-clinical models is expected to bring about a more accurate characterization of cancer stem cells and a clearer understanding of the gene determinants of the phenotype of normal stem cells versus cancer stem cells. The research project is expected to deliver effective diagnostic markers and treatment strategies targeting cancer stem cells. Researchers will primarily use genetically-modified animal models and cellular lines to investigate the role of specific cancer genes in the transformation of stem cells and cancer growth as well as technology platforms to generate expression profiles.
GENETIC AND EPIGENETIC CONTROL OF GENOME STABILITY
Principal Investigator: Silvano Riva
Technology Platform: Genetics
Lead research organization : Consiglio Nazionale delle Ricerche (National Research Council)
Registered Office: Rome
Research conducted in: Pavia
Award: €924,000
This research project aims at gaining a better understanding of the systems involved in genome stability by identifying new genes and gene interactions, and by investigating the role of chromatin organization (epigenetics). Comparative functional genomics integrated analyses, both in vivo and in vitro, will be applied to three model systems: yeast, Xenopus and human cells. The project will use sophisticated techniques like in vivo imaging to analyze molecular dynamics in the proteins involved in damage repair, checkpoints and chromatin alterations.
Specific objectives: :
Identifying at genome level the interactions between checkpoint, replication and reparation pathways and epigenetic control.
Developing methods to identify human genes involved in genome stability.
Identifying the function of said genes and the pathways specifically involved in the pathogenesis of genetic disorders with defective response to DNA damage.
Expected results: understanding how changes in pathway genes responsible for genome integrity influence the pathologic phenotype and the effectiveness of cancer treatments, as well as designing new strategies based on the development of new bio-active molecules for the selective elimination of cancer cells.
HIGH-TECH NETWORK FOR THE GENERATION AND USE OF ANIMAL MODELS FOR GENE AND CELL THERAPY OF HUMAN DISEASES
Principal Investigator: Paolo Vezzoni
Technology Platform: Animal Models
Lead research organization : Consiglio Nazionale delle Ricerche (National Research Council)
Registered Office: Milan
Research conducted in: Milan
Award: €1 million
The main objective of this project is to leverage a combined technology platform that ensures the availability in Lombardy of all technologies and competences needed for the production and use of animal models for testing treatments for human disorders, employing both traditional and innovative approaches like cell therapy and gene therapy. The primary objective is to generate, analyze and use animal models. A further objective is to continuously upgrade the new technologies in this field as they become available internationally. In addition to ensuring the competences described above, the network intends to actively engage in the training of young scientists coming from Lombardy’s research centers.
GENO PROTEOMICS OF AGE RELATED DISORDERS (GuARD)
Principal Investigators: Giampaolo Merlini and Roberto Sitia
Technology Platform: Gene Expression
Lead research organization : Consiglio Nazionale delle Ricerche (National Research Council)
Registered Office: Milan
Research conducted in: Milan
Award: €3.5 million
Since people live longer, the disorders affecting the populations of the western world are rapidly changing due to longer life expectancy. Generically, age-related disorders can be classified into two categories: degenerative disorders and cancer. A trait shared by degenerative disorders, like Alzheimer’s disease, Parkinson’s disease and systemic amyloidoses, is the presence of pathogenic misfolded proteins. The research project will therefore try to find an answer to the following questions: Why and how do misfolded proteins aggregate? Why are different proteins selectively toxic for certain types of cells and tissues? How can molecular knowledge be translated into new treatment strategies and options?
Research efforts will be directed to:
identify the genes involved in the onset and the progression of these disorders;
identify new targets for early diagnosis and effective treatment of diseases;
identify the molecular determinants that influence the response to treatment through pharmacogenomic analyses.
For the achievement of these scientific objectives, existing facilities will be integrated with newly developed ad-hoc technology services. The platform will be made available to partners for validation and then offered to the scientific community. The services offered will relate, in particular, to the expression-purification and characterization of proteins, genotyping and transcriptomics, proteomic analyses.
A GENETIC TOOLKIT FOR THE ANALYSIS OF MOUSE NEURAL STEM CELLS (ACRONYM: NS-TOOLKIT)
Principal Investigator: Elena Cattaneo
Technology Platform: Animal Models
Lead research organization : Università degli Studi di Milano (Milan University)
Registered Office: Milan
Research conducted in: Milan
Award: €1million
Cell replacement therapy is considered one of the most promising avenues in the search for new treatments for brain lesions and neurodegenerative disorders. It is based on the idea that implanted cells may regenerate interrupted circuits or repair damaged tissues by producing growth factors or immunomodulators. The effective application of neural stem cells in molecular medicine, however, is hampered by the lack of tools that enable their isolation and propagation, as well as the limited amount of information on the mechanisms governing their proliferation and self-renewal, as well as their differentiation. The project will leverage the potential of animal transgenesis and mouse genetic models to take full advantage of the consistency, stability and neurogenic action of neural stem cells. The purpose of this combined strategy is to screen the mouse genome and transcriptome to identify a broad sample of molecular determinants of neural stem cell specification and neural differentiation. This approach will be based on the combination of existing and new transgenic lines from which a large number of engineered and specialized neural stem cell lines will be derived. The project will provide the scientific community and selected biotechnology and pharmaceutical companies with an optimized operational tool for the application of molecular screening to stem cells.
GENETIC AND FUNCTIONAL GENOMICS OF MYELOMONOCYTIC CELLS
Principal Investigator: Alberto Mantovani
Technology Platform: Genetics
Lead research organization : Consiglio Nazionale delle Ricerche (National Research Council)
Registered Office: Milan
Research conducted in: Milan
Award: €2 million
The overall objective of this project is to build a technology platform to explore some key components of the inborn immune system’s genetics and functional genomics and to make this platform portable. The technology platform will be built by leveraging and enhancing various complementary technologies contributed by the project partners. It will be accessible to Lombardy’s scientists. The overall research strategy underpinning the project will include a research line focused on identifying new genes and new molecular signatures associated with natural immunity cells. These studies will be based on complementary molecular genetics and post-genomics approaches. The platform’s molecular genetics approaches include conventional genetic techniques, transcriptional profiles, identification of genes and gene families via bioinformatics, and the creation of genetically modified animals. Genetic and post-genomic approaches will be supplemented by functional tests to assess natural immunity functions. One of the platform’s key features will be immunohistochemistry and immunohistopathology techniques that are instrumental to exploring the inborn immune system.
MOLECULAR MODELING IN GENE TRANSCRIPTION, TRANSLATION AND REGULATION
Principal Investigator: Corrado Priami
Technology Platform: Bioinformatics
Lead Organization: The Microsoft Research – University of Trento Centre for Computational and Systems Biology
Registered Office: Trento
Research conducted in: Povo (Trento)
Award from Fondazione Cariplo: €600,000
Award from Fondazione CariTRo: €600,000
This project focuses on the bio-inspired definition of new modeling tools and languages which have been adapted to represent and analyze the time-dependent behavior and properties of complex systems made up of many different components that compete, cooperate and communicate with one another. Starting from relevant complex examples provided by a series of biological case studies that were selected by the other partners in the NOBEL platform, the project is designed to identify key modeling features in order to understand and characterize their modularity, self-organization and hierarchy and define a sectional, scalable framework which supplements modeling and assessment characteristics to analyze and predict system behaviors and expand knowledge. The involvement in the project of biology scientists to conduct experimental living-cells reverse-engineering research is key. The close collaboration of ICT experts with system analysis specialists (reverse engineering) and molecular bio-scientists enables the integration of the various fields of knowledge and will lead to results which can be applied by both scientific communities. The resulting modeling framework will be subject to validation against the biological case studies used to determine the framework requirements.