To give an insight into the mechanisms of protein folding. To acquire knowledge on inborn errors of metabolism and on common mechanisms of acute and chronic neurodegenerations. To underatnd the role of biomarkers in clinical biochemistry. To supply a vast overview of the molecular mechanism involved in cancer development and progression.
In this part of the course, it will be given an overview of the most challenging and evokative topics of the most diffuse degenerative pathology, cancer. In particular basic and more complex concepts explained in the undergraduated course of Molecular Biology will be deepened, and an explanation of the disregulation of the cellular molecular mechanisms will be presented. The aim of the course, at the end, is to unveal to the student the importance of the disregulation of basic cellular molecular processes in this bad degenerative pathology.
The lectures will be delvered ex-cathedra, with the support of ppt slides that will be available to the student in the STUDIUM web platform.
Short summary of the structure of proteins: the peptide bond, primary, secondary, tertiary and quaternary structure. Super-secondary structures. Structural and functional protein domains. Th folding of proteins. Thermodynamic of protein folding. Spontaneity of protein folding. The role of the S-S bridges in the stabilization of the partially folded proteins. The molten globule. The Anfisen paradox. The assisted protein folding and the chaperonines. Classification of eucariotic and procariotic chaperonins. Structure and function of Gro-Es e Gro-El. The chaperonpathies: examples of hereditary e non-hereditary pathologies related to protein misfolding.
The point mutatios: relationship between changes in the structure and function of mutated proteins. Rare diseases: the inborn errors of metabolism (IEM). Examples of IEM related to the metabolism of glycogen, purines and pyrimidines, organic acids, amino acids and N-acetylaspartate (NAA).
Approaches for the clinical-biochemical diagnosis of IEM. Main analytical techniques for the clinical-biochemical diagnosis of IEM. Prenatal and postnatal diagnoses of IEM. Small scale and large scale screenings of IEM.
Biomarkers: definition, characteristics and validation.
General characteristics of the main enzymes of clinical relevance and their changes under pathological conditions. Laboratory analyses associated to atherosclerotic risk factors. Tumoral biomarkers and their use in oncologic diagnosis. The metabolic syndrome. Laboratory diagnosis of autoimmune diseases. Common biochemical changes associated with acute and chronic neurodegenerative pathologies. traumatic brain injury and multiple sclerosis. NAA as a biomarker of neuronal integrity. Introduction to homeostasis of NAA under physiological and pathological conditions.
Cancer: cellular and epidemiological aspects – risk factors
Tumor suppressor genes - pRB
Cell cycle and its control
Apoptosis - role of p53
Telomer and cancer immortality
Importance of genome integrity
1) Struttura e funzione delle proteine, Petsko e Ringe, Zanichelli
2) Ad hoc materials supplied to students (scientific papers, slides, etc.)
L. Pecorino Biologia molecolare del cancro Zanichelli 2010
R.A. Weinberg La Biologia del Cancro Zanichelli 2016
Two american textbooks, translated in italian, but whose original text are easily available