The aim of the course is to provide a deep knowledge of the structural/functional properties of cellular membranes and the signaling processes through which the information reaches intracellular targets. We will discuss about: - functional effects of lipid-lipid and lipid-proteins interactions; - the passive and active properties of the plasma membrane and in particular with the molecular mechanism governing cell excitability and propagation of the electrical signals; - the functional importance of specialized membrane organizations; - the basic concepts of cellular signal transduction; - the functioning and modulation of kinases, phosphatases, G-protein coupled receptors, intracellular receptors; - the mechanistic complexities underlying the conversion of diverse stimuli into a series of intracellular reactions through signal transduction pathways; - the molecular mechanisms through which the signal transduction pathways communicate information to gene expression programs; - recent advances on the potential impact of signaling pathways in human diseases.
Expected learning outcomes
Students are expected to be able to master the processes by which the biological signals (electrical and biochemical signals) are generated and pass through the plasma membrane and reach the intracellular targets. Students are expected to be able to understand how lipids, receptors, ion channels and signaling molecules interplay in generating cell responses to stimuli.
Lesson period: Second semester
(In case of multiple editions, please check the period, as it may vary)
MEMBRANE BIOPHYSICS: Basic principles of biomembranes composition. Lipids and proteins interactions. Lipids as signaling molecules Membrane microdomains, lipid rafts and caveolae. Caveolin-1 , 2 and 3. Role of caveolae and caveolin-interacting proteins. Passive electrical properties of excitable membranes; Equivalent electrical RC model of cellular membranes. The concept and consequences of time and space constants in neuronal excitability. Electrotonic conduction of the electrical signal along a membrane. The action potentials of excitable cells: the Hodgkin and Huxley model of the neuronal action potential and the description of the cardiac action potentials. Ion channels function and structure. Specific examples of the effect of lipid microdomains on the kinetic properties of ion channels and consequences for membrane excitability Examples of specific biomembrane organizations: 1- the couplons in skeletal muscle and cardiomyocytes and how they affect Excitation contraction coupling properties. 2- The neuromuscular juncton as a paradigm of mutual functional interaction of biomembranes of different cells. SIGNAL TRANSDUCTION: Basic concepts of cellular signal transduction. Signal inputs and outputs. Classes of signaling components: small G proteins, kinases, phosphatases, adaptor proteins, and cytoskeletal elements. Organization of signaling pathways into networks. Classes of interconnections: junctions and nodes. Examples of junctions and nodes. The receptor tyrosine kinases as one of the best upstream examples of a node. TOR: a molecule with dual identity. Regulation of mTORC1 activity by nutrients and/or alterations in cellular energetics. mTORC1 signaling to the translational apparatus. Recent advances in pharmacological tools and technologies (polysome and ribosome profiling) enabling genome-wide monitoring of changes in translatome. Examples of human disorders and diseases linked to defective translational control. The unfolded protein response (UPR) signaling node. UPR signal transducers and downstream effectors. mTOR-ER stress intersections. Pathogenic features of prolonged ER stress. Dynamics of signaling complexes in different cell types. T cells versus neurons: an example of an identical signaling network with a different logic of the circuitry. Mechanisms of signal consolidation.
Prerequisites for admission
it is recomended to have solid basis of Physics, General Physiology and Biochemistry
The course is divided into a series of interactive classroom lectures in which students are invited to actively participate through questions. The lessons are supported by the projection of didactic material which is however supplemented by explanations on the blackboard.
PDF of the slides from each lecture and scientific articles discusses during lectures will be available as pdf files in the Ariel website of the course. Textbooks: Kandel Principle of Neural Science (Chapter 6 and 7 of 3rd edition) Hille, Ionic Channels of Excitable Membranes Signal Transduction: Principles, Pathways, and Processes (Cold Spring Harbor Laboratory press)
Assessment methods and Criteria
Oral examination constituted by 3-4 questions that assess the ability of the student to connect the topics touched during the course.