Intracellular signaling and trafficking in cancer and rare diseases.
Several cell biology groups at the IBBC have traditionally worked in two related areas of cell biology, namely, signal transduction and intracellular membrane transport. The general objective is to investigate at the molecular level basic biological processes and exploit this knowledge to design novel drug-based therapies, and novel diagnostic approaches, in the fields of cancer and rare diseases. Specifically, the main research areas of these groups are:
• Metabolism of the glycerophosphoinositols and of phosphatidic acid, G-protein-coupled receptors, and the ADP-ribosylation reaction; the general aim is to elucidate the cellular regulatory mechanisms that, when defective, lead to rare diseases and cancer.
• Investigation of the organizational principles and regulation of intracellular cargo transport and organelle structure; development of the required cellular models and technologies (including imaging, systems biology, bioinformatics and modeling approaches); pharmacological approaches for cancer and other diseases related to membrane transport.
• Development of advanced optical technologies based on Raman Spectroscopy and Mass Imaging to provide novel procedures for label-free characterization of single cells and single molecules.
identification and use of natural substances
While modern medicine is focused on overcoming diseases of genetic, age-associated and life-style origin, the emergence of new viral pathogens and antibiotic resistant bacteria have opened a new frontier. The interests of several groups at IBBC lie in the development of cellular model systems that recapitulate the pathology of these diseases, using these systems for understanding the molecular basis of pathogenesis as well as for developing potential therapeutic interventions that can be translated to the clinic. The major diseases that are being studied include Cystic Fibrosis, Wilsons disease, congenital disorders of glycosylation, cancer, metabolic and neurological diseases, and viral infectious diseases.
The different groups also have strong collaborations with industries including Dompé and, together with the chemo-bioinformatics facility at the IBBC in Naples, aim at identifying and developing small-molecule-based therapeutic strategies for pharmacological interventions.
Generation, cryopreservation and phenotyping of murine mutants model of human diseases, Infrafrontier-Emma European infrastructure
CNR has established and developed at the A. Buzzati-Traverso Campus in Monterotondo the European Mouse Mutant Archive (EMMA) Core Structure and Monterotondo Mouse Clinic (MMC), as advanced international infrastructures for the life sciences, in collaboration with the leading, European and extra-European biomedical research Institutions. The EMMA Core Structure and MMC are devoted to large-scale, standardized production, primary and specialized phenotypic analysis, cryopreservation and dissemination of novel murine mutant models of human diseases with their bioinformatics resources.
The EMMA Core Structure and MMC are essential component of the INFRAFRONTIER network infrastructure, a Landmark Project of the European Strategy Forum on Research Infrastructures (ESFRI) Roadmap and a selected project of the Italian Ministry of Research’s Roadmap and National Programme on Research Infrastructures (PNIR). CNR-EMMA, Monterotondo is the Italian co-founder and partner of INFRAFRONTIER.
imaging and microscopy, biosensors, European Eurobioimaging infrastructure
The Bioimaging group is interested in developing novel imaging methods to visualize processes of life at the cellular level.
Specifically, we are interested in imaging protein-protein interactions and metabolites, especially lipids.
The methods for visualization range from classic fluorescence and electron microscopy to modern correlative light-electron microscopy and super-resolution microscopy.
molecular, cellular and behavioral aspects, neuropathologies and aging
Researches focus on mechanisms regulating brain functional states under physiological and pathological conditions in cells and mouse models. Main themes include the study of development and plasticity, emotionality, movement disorders, learning and memory, response to acute and chronic stress and pain, central control of energy homeostasis and reward, depression, aging and neurodegeneration, brain tumors. The role played by mouse genetic background, neurogenesis, microbioma, hormonal, neuroimmune systems, LncRNA/miRNA-mediated regulation and neurotrophins are investigated. Genetically manipulated animals and cellular models are used to clarify the role of genes in neural stem cell control and in different pathologies related to CNS and PNS functions. Transcriptomic and proteomic analyses are carried out, in order to identify new target molecules involved in physiological and/or pathological processes. Molecular, histological and behavioral characterizations provide tools to detect pathological conditions and evaluate rescuing strategies, in a translational perspective.Read More
identification of molecular targets and drug development
Several IBBC researches are focused on the investigation of molecular and cellular mechanisms leading to cell transformation, cancer development and progression. This requires the integration of different experimental approaches, including profile-based screening of gene expression, bioinformatics analysis, phenotypical and biochemical characterization of genetically modified cellular and murine models.
Numerous cancer-associated processes are investigated. These include gene expression (mRNA, lncRNA, and miRNA), genome instability, lipid metabolism, DNA damage response, cell growth, apoptosis, hormone-dependency, differentiation, angiogenesis, cell invasion, cell-cell and cell-extracellular matrix interactions. The most investigated tumor models comprise leukemias, epithelial tumors (breast, lung, thyroid, head and neck, prostate, ovarian), brain and nervous system tumors.
A better understanding of the mechanisms regulating the activation of selected oncogenes and tumor suppressors genes, signaling pathways and mediators are instrumental in identifying cellular, biochemical, and molecular pathways involved in cancer biology and mechanisms of resistance to target therapies and valuable targets for the development of innovative anti-cancer drugs and treatments for unmet medical needs.
Striated muscle (skeletal and cardiac) is the most abundant tissue of the body and plays an essential role in systemic metabolism and movement. Skeletal and cardiac muscles can be affected by many severe pathological conditions, including diseases of genetic and traumatic origin, systemic metabolic disorders, neuromuscular and age-associated chronic pathologies. The research projects in this area focus on defining pathogenetic regulatory mechanisms and identifying disease modifiers. To these aims, researchers at IBBC exploit home-generated or existing cellular and animal models of neuromuscular diseases, such as Duchenne, Myotonic and FSHD muscular dystrophies, amyotrophic lateral sclerosis and spinal muscular atrophy.
The ultimate goal of these different research interests converge on the development of novel strategies for tissue regeneration and for treatment of neuromuscular disease, as well as innovative prognostic/diagnostic toolsRead More
The IBBC Immunity and Infection groups address different aspects of immunity and infection in order to exploit evolution, physiology and pathology from basic life science and molecular mechanisms studies to the design of innovative tools and strategies for disease prevention and therapy. To this end, IBBC Immunity and infectious diseases groups tackle the following aspects:
• Evolutionary studies for better understanding the mechanisms at the basis of the adaptive immune response. Design of novel diagnostic/therapeutic tools (engineered high performance antibodies; innate, B- and T-cell receptors)
• Targeted vaccination and immunotherapeutic strategies using novel nano-carriers
• Dissecting the interaction between food proteins, microflora and gastrointestinal immune system in health and disease; devising the immunomodulatory approaches for treatment of chronic intestinal diseases
• Exploiting knowledge of inflammation and innate memory mechanisms in the induction of protective immunity (antigen delivery and adjuvanticity of vaccines), and in the therapeutic approach to tissue-specific diseases (chronic inflammatory, degenerative and autoimmune diseases)
• Schistosoma mansoni biology studies mainly focused on male and female reproductive organs and egg production. Identification and characterization of potentially relevant targets and novel anti-schistosomal compounds to tackle schistosomiasis, one the 17 NTDs Neglected Tropical Diseases (NTDs) Neglected Tropical Diseases (NTDs) prioritized by the WHO , and affecting the most poor and vulnerable populations in the world
intracellular signaling and trafficking
Several cell biology groups at the IBBC have traditionally worked in two overlapping areas of cell biology, namely, signal transduction and intracellular membrane transport. The general objective is to investigate at the molecular level basic biological processes and exploit this knowledge to design novel drug-based therapies, and novel diagnostic approaches, in the fields of cancer and rare diseases.
Specifically, the main research areas of these groups are:
– Metabolism of the glycerophosphoinositols and of phosphatidic acid, G-protein-coupled receptors, and the ADP-ribosylation reaction; the general aim is to elucidate the cellular regulatory mechanisms that, when defective, lead to rare diseases and cancer.
– Development of strategies, cellular models, and technologies (including imaging and systems biology approaches) for the investigation of the organizational principles and regulation of cargo transport across membrane compartments; pharmacological approaches for diseases related to membrane transport.
– Structure and function of intracellular organelles during cell division and their role in the regulation of cell cycle, with implications in the definition of novel drug-based strategies to inhibit proliferation of cancer cells.
– Develop advanced optical technologies based on Raman Spectroscopy to provide novel and reliable procedures for label-free characterization of single cells and single molecules.