CORE CURRICULUM II
SPRING SEMESTER
Module 3
Cell Biology I
(16 hours, Coordinator – P. Baas)
This module is designed to provide a general introduction to cell structure. Topics include cytoskeleton, cell adhesion, and methods for imaging cells using contemporary microscopes and computer technology.
Cytoskeleton (2 hrs) - P. Baas
This lecture begins with an overview of the functions of the cytoskeleton, and the three major polymeric filaments that comprise the cytoskeleton in eukaryotic cells. The lecture then focuses on microtubules and how their assembly is regulated.
Microtubules (2 hrs) - P. Baas
This lecture continues with microtubules, and focuses on their interactions with molecular motor proteins as well as the mechanisms by which microtubules are organized in cells.
Actin/Myosin (2 hrs) - B. Moreland
This lecture focuses on the functions of actin filaments in living cells, and the mechanisms by which they are regulated and organized. A number of different actin regulatory proteins are discussed, with a particular emphasis on the myosin family of molecular motors that impose forces on actin filaments.
Cell Adhesion (2 hrs) - Y. Huang
This lecture focuses on the various types of cell junctions and modes for adhesion of cells to other cells and substrates. Topics include embryogenesis, immune cell chemotaxis, tumor cell metastasis, as well as the types of adhesion molecules involved in these processes and events.
Cell Motility (2 hrs) - G. Gallo
This lecture utilizes information from the previous four lectures to provide a detailed view of how cells locomote through their environment.
Mitochondria (2 hrs) - A. Vaidya
This lecture deals with the variety of critical roles played by mitochondria in cellular physiology. Evolutionary origins of mitochondria and the vast divergence of mitochondrial functions in different eukaryotic lineage are discussed. In addition to the energy generation, the importance of mitochondria in regulating calcium levels in the cell as well the triggering of the apoptotic pathway is described.
Stem Cells (2 hrs) - I. Fischer
The objectives of this lecture are to define stem cells and appreciate the diversity of embryonic and adult stem cells, explore the fundamentals of embryonic stem cells (ES) and the technical and ethical issues associated with their use. The therapeutic potential of stem cells, the emergence of regenerative medicine and the concerns about cancer stem cells will be discussed.
Module 4
Cell Biology II
(14 hours, Coordinator – E. Noguchi)
This module will cover basic membrane transport processes, the ionic basis of membrane excitability, various types of ion channels, the process and role of endocytosis in cell function, steps in folding of nascent proteins and protein degradation, protein import into various organelles including the nucleus, ER and mitochondria, and protein processing and trafficking via the Golgi.
Membrane Transport (2 hrs) - M. White
This lecture will introduce the basic physiochemical principles of solute diffusion across membranes. The major classes of transport systems (Passive or Facilitated Diffusion, Cotransporters or Secondary Active Transporters, Ion Pumps or Active transporters) are discussed, with examples of each type. Structural features of membrane transporters are also presented.
Membrane Potentials and Action Potentials (2 hrs) - M. White
In this lecture the basics of diffusion or Nernst potentials are introduced, and then this is extended to cases where more than one ion is permeant. The Hodgkin-Katz-Goldman framework for generation of membrane potentials, the ionic basis of action potentials, with an emphasis on the Hodgkin-Huxley experimental underpinnings and the basics of synaptic transmission will be discussed.
Ion Channels (2 hrs) - M. White
This lecture will continue with a discussion of membrane proteins and cover the classification of ion channels into ligand-gated vs voltage-gated channels. Pre-cloning studies of ion channels to delineate mechanisms of activation in ionic selectivity, the application of molecular biological techniques to probe structure-function relationships in ion channels as well as the structural basis of ion channel activation and ionic selectivity will be discussed.
Protein Trafficking: Nucleus, ER, and Mitochondria (2 hrs) - R. Nichols
The general strategies by which proteins are transported into various organelles will be discussed. The specific mechanisms and players involved in transport into the nucleus, endoplasmic reticulum and mitochondria will then be described in detail, including unique experimental approaches used to uncover the transport processes.
Protein Trafficking: ER to Golgi and Beyond (2 hrs) - Y. Huang
Protein trafficking from the ER through the Golgi Complex via the secretory pathway will be described. In particular, the dynamic nature of the Golgi will be discussed, including vesicle formation, vesicle targeting, vesicle fusion, vesicle vs. cisternal maturation, and sorting at the Trans-Golgi Network.
Phagocytosis and Endocytosis (2 hrs) - A. Vaidya
Molecular details of phagocytosis by professional and non-professional cells are introduced. The “eat me”, “don’t eat me” and “find me” signals in the removal of apoptotic cells are described. Clathrin-mediated and clathrin-independent mechanisms of endocytosis are discussed.
Protein Folding & Degradation (2 hrs) - E. Noguchi
The lecture will focus on how proteins are targeted for degradation by ubiquitin-mediated proteolysis. The role of protein degradation in the cellular processes will be highlighted by a discussion of protein turnover in relation to the regulation of the cell cycle and DNA replication.
Module 5
Cell Signaling and Cell Cycle
(14 hours, Coordinator - R. Raghupathi)
In this module, the students will learn the principles of intracellular signaling, events that occur when a ligand binds to its cognate receptor. In the first part of the module the lectures will cover aspects related to the individual components of intracellular signaling pathways from receptor-ligand interactions to modulators to second messengers to effectors. In the second part of the module, the students will be exposed to signaling aspects associated with cell cycle, cell growth (cancer) and cell death (apoptosis).
Overview, Receptors (2 hrs) - R. Raghupathi
This lecture will present an overview of signal transduction including a discussion of the components involved, different type of signaling as well as divergence and convergence in signaling pathways. The second part of the lecture will focus on the types of receptors in cell signaling, how they function, how they are turned on and turned off and how they can be studied in the lab.
Calcium and cAMP Signaling (2 hrs) - A. Fatatis
This lecture focuses on the cellular structures and mechanisms responsible for the generation and modulation of Ca signals. Free cytosolic Ca is a crucial second messenger for metazoan cells. A large number of cellular events, ranging from secretion and motility to proliferation and death are modulated by the spatial and temporal characteristics of Ca signals.
Protein Kinases and Phosphatases (2 hrs) - R. Raghupathi
The first part of this lecture will cover the biochemistry of phosphorylation and the structure, activation and regulation of members of the protein kinase families (Ser-Thr kinases, tyrosine kinases) and the role of protein kinases in DNA repair, cell structure and motility. The second part of this lecture will then focus on structure, function, specificity, trafficking and regulation of the major classes of protein phosphatases.
Cell Cycle (2 hrs) - B. Bergman
A cell divides by utilizing a precise pathway of distinct orderly events, in which it duplicates its contents and then divides to produce two cells. This cycle of duplication and division is the essential mechanism by which all living cells divide. This lecture will discuss the complex network of regulatory proteins that control this process of cell division in eukaryotic cells.
Apoptosis (2 hrs) - P. Katsikis
This lecture will cover the definitions of apoptosis and necrosis, the morphological and biochemical characteristics of these forms of death, the role of apoptosis, the fate of apoptotic cells, the caspase and Bcl-2 families of molecules, death receptor signaling and mitochondrial participation in apoptosis.
G Proteins (2 hrs) - O. Meucci
This lecture will cover G-protein structure, mechanism of action, and function. Examples of the role of G proteins in normal cell signaling and in disease processes will be provided with a major focus on G-protein coupled receptors (GPCRs).
Lipids/Signaling (2 hrs) - T. Edlind
Membrane homeostasis requires signaling mechanisms that respond to membrane stress and maintain proper levels of phospholipids and sterols. Lipids such as sphingosine-1-P play roles in intercellular signaling, while others such as ceramide and diacylglycerol have intracellular signaling roles. Selected lipid signaling pathways, from yeast to humans, and their role in disease and therapy, will be discussed.
Module 6
Cells to Systems
(16 hours, Coordinator – J. Burns)
This module will provide an introduction to aspects of the nervous system, neuroendocrinology, cardiovascular physiology and the immune system as a means of illustrating the integration of molecular and cellular biological functions in the intact organism.
Nervous System I & II (4 hrs) - B. Waterhouse
The mammalian nervous system is an intricate machine that relies on the appropriate functioning of molecular processes, biochemical pathways, cellular physiology, and neural network dynamics to achieve the complexities associated with sensation, movement, and thought. Dysfunction at any biological level in this system results in debilitating neurologic and/or psychiatric disorders. In the neuroscience segment of the Cells to Systems module we will use the somatosensory system to illustrate how molecules, cells, and circuits come together to detect, code, transmit, and modulate the sensation of touch.
Neuroendocrinology of Energy Balance (2 hrs) - K. Simansky
The efficient regulation of energy balance is essential for the survival. This session will describe the diverse mechanisms by which mammals regulate energy intake (through eating) as one side of the equation. We will 1) discuss the historical basis for the current view of a coordinated network of neural pathways in the brain and in the periphery that control eating and satiation ("fullness"); 2) identify the specific neuropeptides and neurotransmitters that mediate the actions of the network; 3) analyze how endocrine signals from peripheral tissues influence the activity of neurons in the network and the expression of genes for the target neuropeptides; and 4) define the cellular mechanisms at the receptor and post-receptor levels that modulate the transduction of the endocrine signals.
Cardiovascular System I (2 hrs) - T. Wilson
In these two hours of lecture, we will discuss the following three questions: a) how and why does an organism circulate fluid; b) how does an organism get the circulating fluid to the correct location; and c) how is circulating pressure and volume regulated.
Cardiovascular System II (2 hrs) - T. Wilson
The first hour of lecture will continue from Cardiovascular System I. Then, because an organism does not exist in a static environment, in the last hour we will extend and apply the principles discussed previously to understand how cardiovascular system regulated during and adapts to stressful conditions?
Immune System I (2 hrs) - J. Burns
This lecture will provide an overview of the immune system. We will discuss the early, first line of innate defenses to infection and how this response develops over time into a customized, pathogen-specific adaptive immune response. We will describe the primary cells and tissues of the body that comprise the immune system. We will discuss the basic functions of these cells of the immune system, their distribution throughout the body and how these cells interact and communicate with one another following the initial encounter with a pathogen.
Immune System II (2 hrs) - J. Burns
In this lecture, we will follow the development of an immune response to a bacterial pathogen that is encountered in the respiratory lower respiratory tract. A major focus of the lecture will involve antibody-mediated mechanisms of immunity that are important in the clearance of extracellular pathogens. We will specifically discuss similarities and differences in the receptors used by cells of the innate and adaptive immune system to recognize bacteria, the molecular basis by which the diversity of pathogen-specific receptors on lymphocytes is generated and finally, the mechanisms by which cells of the innate and adaptive immune response and their soluble mediators interact and cooperate to kill and/or clear extracellular pathogens.
Immune System III (2 hrs) - P. Katsikis
Cell-mediated mechanisms of immunity represent the second major arm of the immune systems and are important in the clearance of intracellular pathogens including viruses. This lecture will cover natural killer (NK) cells of the innate immune response and adaptive T cell mediated responses. A focus of this lecture will involve the manner in which these lymphocyte populations cooperate to defend against viral infection. The function and activation of NK cells early during the immune response will be described. The role of dendritic cells and the costimulatory receptors and soluble cytokines necessary for the initiation and development of T cell responses will be discussed. CD4+ T cell and CD8+ T cell populations and their functions will be described. Finally, distinct subsets of T helper 1 and T helper 2 CD4+ T cells will be introduced.
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