> Nucleus/ cytoplasm/ mitochondria crosstalk in cellular homeostasis
Nucleus/ cytoplasm/ mitochondria crosstalk in cellular homeostasis
CNR personell: Antonella Bobba, Anna Atlante, Lidia de Bari, Sergio Giannattasio,
Nicoletta Guaragnella, Loredana Moro, Vito Antonio Petragallo, Rosa Anna Vacca, Daniela Valenti.
Research associate: Maria Barile, Ersilia Marra.
Objective of the research is the study of signaling pathways and mitochondrial metabolism in different models of neurodegenerative/neurodevelopmental diseases and in cancer. The delicate balance between cell death and proliferation is essential to the genesis of various pathologies and the mitochondria are proving to be the key factors in regulating: cell growth and death, intracellular signaling and integration of stress signals. The targets of this research concern: mitochondria-nucleus retrograde communication, modulation of the mitochondrial metabolism in pathophysiological conditions and network of intra and inter-cellular signals in the regulation of proliferation, invasion and cell death. The main scientific objectives are: i) understand how the cell signaling networks regulate decisions of life and death; ii) discover new natural and/or synthetic compounds capable of interfering with the disease for future applications in the pharmacological field.
- Study and characterization of mitochondrial metabolism in pathophysiological conditions.
- Characterization of the molecular mechanisms responsible for the pathogenesis of genetic diseases associated with intellectual disability: mitochondrial dysfunction and oxidative stress in Down and Rett syndromes.
- Characterization of signaling pathways activated in the early phase of neurodegeneration and the role of mitochondria in an experimental model of Alzheimer’s Disease.
- Study of new regulatory factors in the programmed cell death of the model organism Saccharomyces cerevisiae; mitochondria-nucleus retrograde communication in the cellular response to stress; biodiversity and applications in biomedicine and bio-food industry.
- Characterization of enzymes involved in the homeostasis of flavin cofactors.
- Study of bioenergetics and glucose metabolism in tumor and identification of new compounds able to induce in vitro death of cancer cells.
- Characterization of the network of intra- and inter-cellular interactions in the regulation of proliferation, invasion and cell death.
- Identification of aberrant signaling pathways that are activated in the process of neoplastic transformation.
Cell systems and model organisms
- Primary cultures of rat cerebellar granule neurons.
- Human drug-resistant cell lines representative of the advanced form of prostate cancer (PC-3, DU145 and C4-2).
- Cell lines of human breast cancer with different degree of invasive potential (MCF-7, MDA-MB-231).
- Human cell lines depleted of mitochondrial DNA [Rho (0)].
- Drug-resistant cell line of human malignant pleural mesothelioma with epithelioid (REN) and biphasic (epithelioid/sarcomatoid, Msto-211H) morphology.
- Human fibroblasts and lymphoblastoid cells with trisomy 21.
- Cell lines of neuronal progenitors (NPCs) isolated from the hippocampus of a mouse model of Down syndrome (Ts65Dn).
- Retro-differentiated human cell lines of neuronal progenitors (iPSCs).
- Yeast cells S. cerevisiae wild-type and mutated.
- Yeast cells expressing human or vegetable proteins
Identification of putative molecular targets involved in neurodevelopment and identification of new therapeutic strategies to improve mitochondrial function and reduce oxidative stress in Down and Rett syndromes.
Identification and characterization of signaling pathways involved in the neurodegenerative process. Study of the pathogenetic mechanism exerted be the toxic peptides of Tau and Beta-amyloid at neuronal level.
Characterization of the mechanisms involved in the regulation of programmed cell death in S. cerevisiae; role of mitochondria in cellular response to stress and resistance to cell death; mitochondria-nucleus retrograde signaling; heterologous expression of BRCA2 and the study of its effect on cell growth and death; heterologous expression of plant viral proteins and effect on the processes of cell growth and death.
Study of the energetic metabolism of the tumor and identification of new metabolic pathways as potential targets for the development of specific anti-cancer therapies. Characterization of molecules/membrane molecular complexes involved in tumor invasion. Role of mitochondrial DNA mutations in tumor progression and metastasis. Identification of new signaling pathways altered at the beginning and during tumor progression.
Mitochondrial energy metabolism in fibroblasts and human lymphoblastoid with trisomy 21 (DS): effect of treatment with epigallocatechin 3-gallate (EGCG)
Study of bioenergetics and glucose metabolism of the tumor. The metabolism of the isomers of lactate in cells of the human prostate normal and tumor cells, cultured
Mechanisms of programmed cell death induced by acetic acid in cells of the yeast Saccharomyces cerevisiae