EUKARYOTIC CELL: compartments and specialization. Cytoplasmic organelles: nucleus, endoplasmic reticulum. Post-translational modifications, protein localization, co-translational and post-translational import/export mechanisms. Communication with Golgi apparatus, plasma membrane. Mechanisms of communication with extracellular environment and signals’ reception. Somatic and germinal cells.
CELL DIFFERENTIATION AND ITS MECHANISMS. Principles governing differentiation and histogenesis.
Specialized cells and embryonic totipotent and pluripotent stem cells. Adult multipotent and unipotent stem cells. Mitotic and differentiation potential. Stem cells’ properties. Types of stem cells. Stem cells’ niches. Cell proliferation: hyperplasia and hypertrophy. Senescence and cell death. Apoptosis: mechanisms and biological goals.
MECHANISMS OF GENE EXPRESSION REGULATION IN PROKARYOTES AND EUKARYOTES.
GENE EXPRESSION REGULATION. Signals for cell division and differentiation: cell-cell junctions, cell-extracellular matrix junctions, proteic and lipidic growth factors. Autocrine, paracrine, and endocrine action of growth factors. Cell membrane receptors, intracellular cytoplasmic and nuclear receptors: structure, properties and functions in the gene expression regulation.
General principles of extracellular signals’ transduction mechanisms in the biological systems. Tyrosine kinase receptors and seven-domains-transmembrane non-tyrosin kinase receptors. Signal transduction mediated by mitogens to overcome the G1 phase checkpoint of the cell cycle. Signal transduction regulating blood glucose levels.
The extracellular matrix as survival factor and as proliferative factor. Focal and fibrillar adhesion sites. Integrins’ signal transduction. Cell migration. Cross-talk mechanisms between integrins and growth factor tyrosine kinase receptors.
LEVELS OF GENE EXPRESSION REGULATION:
- DNA structure: amplification, somatic mutation.
- DNA transcription: discontinuous structure of eukaryotic gene, start and termination signals of gene transcription. Gene promoter, henancer and silencer. General and specializing transcription factors, activators and repressonr, lipidic hormone-receptor complexes. Transcription factors’ structure. Families of transcription factors: homeotic genes. Alternative promoters.
- Pre-mRNA maturation: capping, alternative splicing, alternative polyadenylation, editing.
- mRNA stability: 5’-UTR and 3’-UTR sequences, deadenylation and decapping, non-sense-mediated mRNA decay.
- Translation and gene expression regulation mechanisms. The post-translation modifications: chemical and proteolytic modifications, proteins’ quality control, chaperone proteins, proteins’ degradation by ubiquitination and proteasome.
BIOLOGY OF DEVELOPMENT. Experimental embryology: principles, experiments of Chabry, Roux, Drisch, Clendon and their interpretation. Embryonic inducers and their properties: experiments of Spemann, Horstadius, Briggs e King, Gurdon.
Embryonic and postnatal cell differentiation: segmentation, morula and blastula phases, gastrulation. Maternal, segmentation and homeotic genes. Morphogenetic gradients and transcription factors’ cascades in Drosophila melanogaster and in humans. Mechanisms regulating differentiated adult state.
Cell cloning and experimental techniques. Induced pluripotent stem cells (IPS cells): in vitro reprogramming of adult specialized cells and their potential uses: IPS cells for the study of pathogenesis, pharmacologic mechanisms’ study and cell therapy. Regenerative medicine by stem cells and IPS cells. Bone marrow transplantation for the treatment of leukemia, skin transplantation for burns and genetic diseases.
DNA MUTATIONS AND REPAIR MECHANISMS. Spontaneous and induced DNA mutations. DNA repair mechanisms and cell senescence, human diseases and cancer.
TUMOR CELL: phenotype and cell growth. Oncogenes, suppressor genes and mutator genes: mechanisms of action.
Dominant mutations in oncogenes; recessive mutations in tumor suppressor genes, loss of heterozygosity: Rb1, WT1 and p53. Gain of function and loss of function mutations. Chromosomal mutations in cancer and in particular in leukemia. Philadelphia chromosome and Burkitt’s leukemia. Knudson’s hypothesis. Familial and sporadic tumors.