Topics include physiology and molecular biology of the cell cycle, computational models of cell cycle control, cancer biology, and basic principles of chemotherapy.
|Tuesday, September 2|
|9:00-10:00am||John Tyson, Virginia Tech: Phases of the cell cycle, logic of the cell cycle, checkpoints, size control in lower eukaryotes, embryonic cell cycles, cyclins and M-phase promoting factor, cell-division-cycle genes, wee mutants of fission yeast, universal control mechanism for the cell cycle.|
|10:30-11:30am||Bela Novak, Technical University of Budapest: Presentation Chemical kinetic models, zero-order ultrasensitivity, molecular antagonism, multiple steady states, limit cycle oscillations, growth and division.|
|Wednesday, September 3|
|9:00-10:00am||John Tyson, Virginia Tech: Fission yeast: G1/S and G2/M transitions, wee1 and cdc25 mutants, re-replication mutants. Budding yeast: Start and Finish transitions, simulation of mutants, computational issues.|
|10:30-11:30am||Bela Novak, Technical University of Budapest: Presentation Dynamical systems, vector fields, bifurcations. Multiple steady states, Hopf bifurcations, infinite-period oscillations. Surveillance mechanisms ("checkpoints") for cell growth, DNA synthesis, chromosome alignment.|
|Thursday, September 4|
|9:00-10:00am||David Axelrod, Rutgers University: Successful completion of the cell cycle typically results in two cells. Each progeny cell may, or may not, remain viable, become quiescent, or continue to cycle and proliferate to form a population of cells. Populations of normal or tumor cells derived from single cells growing in vitro are heterogeneous as measured by the distribution of the number of cells per colony. Two models of heterogeneity will be discussed. One model accounts for the size distribution of the number of cells per colony in terms of variations in the cell cycle. The second model accounts for the inheritance of colony sizes by the inheritance of cell cycle times within a colony. For each model the effect of the ras oncogene on the cell cycle kinetics of tumor cells will be elucidated by comparison of normal and tumor cells. Model simulations will be compared to data. The perspective will be from that of an experimental biologist who has collaborated with applied mathematicians and biostatisticians.|
|10:30-11:30am||David Axelrod, Rutgers University:Tumors are populations of cells derived from single cells. They are clonal but heterogeneous. The change in cell characteristics as the tumor population expands is referred to as tumor progression. Two types of lesions are found together in heterogeneous breast cancers, they are refered to as in situ carcinoma and invasive carcinoma. Their relationship in the progression of the heterogeneous tumors is not known. Three models of pathways of tumor progression will be described and evaluated by comparison of simulation results with quantitative clinical observations. The model that best reproduces the clinical observations suggests a different relationship between the in situ and the invasive lesions in the progression of heterogeneous breast tumors than the one currently accepted by pathologists.|
|Friday, September 5|
|9:00-10:00am||John Tyson, Virginia Tech: Yeast cell shapes, isotropic and polarized growth, roles of microtubules and filamentous actin, pattern formation in reaction-diffusion-convection equations.|
|10:30-11:30am||Bela Novak, Technical University of Budapest: Presentation "Social" controls of the cell cycle in multicellular organisms, signal transduction pathways that induce or repress cell proliferation, programmed cell death, getting in touch with your "inner yeast."|
Topics include the physiology of calcium dynamics, calcium oscillations and waves, photorecepter physiology, odoreceptor physiology, and physiology of neurosecretory cells.
|Monday, January 5: Calcium Dynamics|
|9:00-10:00am; 11:00-12:00pm||Mike Sanderson, University of Massachusetts Medical School: In my first lecture I shall present the basic physiology of calcium control in non-excitable cells, covering such topics as Ca ATPase pumps, the endoplasmic reticulum and mitochondria, the inositol trisphophate cascade, ryanodine receptors, calcium buffering, calcium-sensitive ion channels, and the control of calcium influx.
In my second lecture I shall discuss the variety of calcium responses observed in different cell types, including baseline spiking, oscillations on a raised baseline, intracellular waves, and intercellular waves. I'll briefly discuss the techniques of calcium dyes and fluorescent microscopy, and end by discussing the physiological function of these waves and oscillations.
|Tuesday, January 6: Constructing and using models of calcium dynamics|
|9:00-10:00am; 11:00-12:00pm||James Sneyd, University of Auckland, New Zealand: Presentation|
|Wednesday, January 7|
|9:00-10:00am; 11:00-12:00pm||Dan Tranchina, Courant Institute, New York University|
|Thursday, January 8: Olfactory Transduction in Vertebrates and Invertebrates|
|9:00-10:00am; 11:00-12:00pm||Johannes Reisert, Johns Hopkins University School of Medicine: Presentation1, Presentation2 The two lectures will focus on the question of how olfactory receptor cells translate the presence of volatile odorants in the air into electrical nerve signals or action potentials. The transduction mechanisms in olfactory receptor cells of vertebrates and invertebrates both employ G protein coupled cascades. Binding of an odor molecule to a receptor protein activates a G protein, which in turn leads to activation of an effector molecule (e.g. phospholipase C or adenylyl cyclase), an increase in second messenger concentration and channel gating, to begin the electrical response. The emphasis of the lectures will be what is known about the level of quantification of individual steps in the transduction process.|
Topics include physiology of synapses, models of synapses, muscle physiology, and models of muscles.
|Monday, March 1: Integrated Calcium Management in Cardiac Myocytes|
|9:00-10:00am; 11:00-12:00pm||Tom Shannon, Rush University Medical Center: The process of cardiac myocyte excitation-contraction coupling is a complex process. There are many systems involved which interact to form varied but well-tuned effects which are essential to contractile regulation. Nearly all of these systems are Ca-dependent and Ca homeostasis within the myocyte is carefully controlled. A great deal of this contractile control originates at the level of Ca transport by 1) the Na-Ca exchanger, 2) the SR Ca-pump which is balanced by a Ca leak out of the SR and 3) various slower systems including transport by mitochondria and the sarcolemmal Ca pump. These systems interact to regulate the amount of Ca within the cell at rest, most of which is stored within the sarcoplasmic reticulum (SR). The release of Ca from the SR is initiated by the process of Ca-dependent Ca release. Ca comes into the cell, primarily through Ca channels, and accumulates within the narrow junctional space between the SR and the cell membrane (or sarcolemma, SL). The amount of Ca released from the SR is dependent both upon the [Ca] within the this space and upon the SR [Ca], specifically the free SR [Ca] ([Ca]SR). The cellular contraction is dependent upon the released Ca and relaxation takes place upon Ca uptake back into the SR or transport back across the SL. In summary, the varied processes responsible for Ca regulation within the cell are critical to the normal functioning heart and disruption of the normal operation of these proteins can cause widely varied pathological effects in large part due to dysfunctional Ca release.|
|Tuesday, March 2: Mechanisms and Models of Cardiac Excitation-Contraction Coupling|
|9:00-10:00am; 11:00-12:00pm||Raimond Winslow, The Johns Hopkins University School of Medicine & Whiting School of Engineering: Presentation Excitation-contraction (EC) coupling is the process by which influx of calcium (Ca2+) ions through voltage-gated membrane channels triggers release of Ca2+ from intracellular stores, leading to muscle contraction. This process is of enormous importance in cardiac muscle, as it not only underlies the process of muscle contraction, but is also involved in regulation of the cardiac action potential. In these tutorials, we will review: a) the structural and biophysical basis of cardiac EC coupling; b) common-pool and local-control models of the EC coupling; and c) the role of EC coupling in modulation of action potential properties; and d) disease-induced deficits in EC coupling and mechanisms of arrhythmia.
(Supported by NIH HL60133, the NIH Specialized Center of Research on Sudden Cardiac Death P50 HL52307, the Whitaker Foundation, the Falk Medical Trust, and IBM Corporation)
|Wednesday, March 3|
|9:00-10:00am; 11:00-12:00pm||Ed Pate, Washington State University - Vancouver: Presentation|
|Thursday, March 4|
|9:00-10:00am; 11:00-12:00pm||Richard Bertram, Florida State University : Presentation1, Presentation2 Models of Calcium-Induced Neurotransmitter Release: Mathematical models of the presynaptic terminal will be discussed, focusing on the key role played by calcium in the exocytosis of transmitter-filled vesicles. We will discuss the reaction diffusion equations that describe the diffusion of calcium ions and their interaction with mobile buffer molecules, and how these equations can be reduced to a single partial differential equation when certain assumptions are made about the buffer. Models of the postsynaptic response to released transmitter will also be discussed, and combined with a simple presynaptic model to simulated the transfer of information from the presynaptic to the postsynaptic cell.
Mathematical Models of Presynaptic Plasticity: Several forms of synaptic plasticity occur at the presynaptic terminal. Forms of plasticity in which neurotransmitter release is enhanced include facilitation, augmentation, and post-tetanic potentiation. Transmitter release can also be depressed through several mechanisms. We will discuss the various forms of presynaptic plasticity and describe mathematical models that have been developed to explain them. The effects of short-term plasticity on information processing will also be discussed.
|Thursday, May 6|
|9:00-10:00am; 10:30-11:30am||Host-microbe interactions, parasitism and pathogenecity. Components of the immune system: molecules, cells, and tissues.
Antigen receptors, somatic diversification and signaling; immune phenomenology: tolerance, immune response, memory, vaccination.
|Friday, May 7|
|9:00-10:00am; 10:30-11:30am||Pathogen evasion of immune defenses. Autoimmunity. Evolutionary and comparative aspects.
Immunological essays, statistical and mathematical models in immunology.
|Tuesday, June 15|
|10:30-12:00pm||Introduction to host-pathogen dynamics.|
|2:00-3:30pm||Obligate steps for pathogens when they interact with the host.|
|Wednesday, June 16|
|9:00-10:00am||Model 1: Using mathematics to model infectious diseases.|
|10:15-11:30am||Examples of modeling immune-viral interactions.|
|1:00-2:30pm||Model 2: Examples of modeling immune-bacterial interactions|