MATHEMATICS IN CELL PHYSIOLOGY AND PROLIFERATION. =================== Second Announcement =================== In the same spirit and hopefully with the same success as the First Summer School, which took place in St. Flour (France 1997), a Second Summer School of Mathematical Biology will take place in Termoli (CB, Italy) between June 6 and June 19, 1999. The school is organized by the French Society for Theoretical Biology (SFBT) and by the Centro Fisiopatologia dello Shock and Istituto Analisi dei Sistemi ed Informatica of the Italian National Research Council (CNR). The school is conducted in close collaboration with the Mario Negri Pharmacological Research Institute. The school is sponsored by: - European Commission - CNR Strategic Project "Metodi e Modelli Matematici nello Studio dei Fenomeni Biologici" - Istituto di Analisi dei Sistemi ed Informatica del CNR - Centro CNR di Studio per la Fisiopatologica dello Shock - Universite' de Pau et des Pays de l'Adour - Rice University, Houston - Comune di Termoli The subject of the school will be mathematical methods applied to the study of cell and molecular biology. The goal of the school is to offer participants a presentation of some mathematical techniques widely used in modelling problems in cell physiology and proliferation, together with a review of some such problems of contemporary relevance. The target audience is mainly composed of advanced graduate students and post-graduates in the life sciences and in mathematical disciplines (math, applied math, physics, engineering). Applications are also encouraged from senior researchers who may wish to explore a different field or take part in interdisciplinary studies. An updated description of the school may be found at the web page http://space.tin.it/scienza/hjcas/biomasch.htm The school can also be contacted at the email address biomath@tin.it The school will be held at the Hotel Meridiano in Termoli. Termoli is a pleasant seaside town in southern Italy, on the Adriatic coast. The town features a tiny medieval village perched on a rocky promontory thrust out on the sea, as well as a modern part towards the interior and along the beaches north and south of the rock. Weather is mild to warm, sunny most of the time. Termoli can be reached by train from the following italian cities: Rome (5 hours), Milan (6.5 hours), Bologna (4.5 hours), Pescara (1 hour), Bari (2 hours), Naples (4.5 hours). Classes: Duration of the school is two weeks, including 11 days of classes, Monday through Friday and Saturday morning. Each day there will be 8 or 9 lecture units of 40 min by the staff and by invited speakers, practice sessions and lectures contributed by participants. Two afternoon sessions each week will be carried out at the Mario Negri Pharmacological Research Institute (Consorzio Mario Negri Sud, Santa Maria Imbaro, Chieti), the purpose being to expose the participants of the school to real-life biological problems. Mario Negri researchers will illustrate their work and show laboratory experimental tecniques and measurements. The language of the school is English. Most school activities will take place in the same hotel where rooms and meals are provided. Each lecture sequence (detailed below) will be completed in a single week, more biological subjects being treated in the first week and more mathematical subjects being treated in the second week. Collected notes will be provided to the school participants. The number of participants is limited to 70. Given the funding obtained from the European Commission and other sources, the standard cost to participants is 750 euro covering all foreseen school activities, including full accomodation (three-star hotel, double room, from Sunday June 6th to Saturday June 19th, 1999), registration fee and teaching material, social programme, transportation to and from the Negri Institute. Further substantial cost reduction (up to the entire cost) is possible for participants qualifying for the following scholarships: TMR (European Commission): scholarships reserved to participants 35 years ofage or younger, from the European Community and affiliated countries (Austria, Belgium, Denmark, Finland, France, Germany, Greece, Ireland, Italy, Luxembourg, the Netherlands, Portugal, Spain, Sweden, United Kingdom, Iceland, Israel, Liechtestein and Norway). INCO (European Commission): scholarships reserved to participants 35 years of age or younger, from Eastern European and assimilated countries (Albania, Armenia, Azerbaidjan, Belarus, Bosnia-Herzegovina, Bulgaria, Cyprus, Czech Republic, Estonia, FYROM, Georgia, Hungary, Latvia, Lithuania, Malta, Moldova, Poland, Rumania, Russia, Slovakia, Slovenia, Turkey, Ukraine). World (School Organizing Committee): scholarships to be assigned by the School independently of TMR or INCO criteria. Prospective participants compiling the (webpage, email, fax or mail) application will receive a Financial Support Form: all scholarships will be assigned on the basis of the academic and financial information submitted in the Financial Support Form. By April 20th, each applicant will receive communication of admission to the school, of proposed support (if appropriate), of the amount to be paid for pre-registration, and of the modalities of payment. Pre- registration is strongly advised to guarantee admission at the conditions outlined above. Calendar: September 1998: First announcement, topics covered February 1999: Second announcement, program and logistics April 15 1999: Deadline for submission of financial support form April 20 1999: Communication of admissions and financial support to participants. Pre-registration opens. May 1 1999: Deadline for submission of contributed presentations May 20 1999: Pre-registration closes. Final announcement. June 1999 Sunday 6 Welcome and registration. Monday 7 School starts Friday 18 School ends Saturday 19 Farewell breakfast, instructors' meeting Scientific Committee: Z. Agur (Israel), O. Arino (France, President), A. De Gaetano(Italy), M.B. Donati(Italy), A. Gandolfi(Italy), M.Kimmel(USA), M. Mackey (Canada), E. Sanchez (Spain), A. Swierniak(Poland), P. Ubezio(Italy). Organizing Committee: O. Arino, A. De Gaetano (Managing Director), A. Gandolfi, M. Kimmel. Instructors and invited lecturers: Zvia Agur, Saverio Alberti, William Amos, Ovide Arino, Michael Beil, Jacques Belair, Edoardo Beretta, Alessandro Bertuzzi, Vincenzo Capasso, Ranajit Chakraborty, William Coleman, Carlo Croce, Andrea DeGaetano, Luigi Del Vecchio, Alberto Gandolfi, Raffaella Giavazzi, Albert Goldbeter, Kristian Helin, Thomas Hoefer, Mimmo Iannelli, Marek Kimmel, Tanya Kostova, Sophie Lelievre, Michael Mackey, Joseph Mahaffy, Luigi Preziosi, Eva Sanchez, Damien Schoevaert, Andrzej Swierniak, Ziad Taib, Paolo Ubezio, Jany Vassy, Vladimir Vatutin, Glenn Webb. TOPICS COVERED IN THE LECTURE SEQUENCES AND INVITED TALKS Note: last minute rearrangements are possible for some lectures. FIRST WEEK ========== TUMOR CELL BIOLOGY (S. Alberti, R. Giavazzi and K. Helin) - Introduction: cell structure and function. - Molecular mechanisms of cell cycle progression. - Deregulation of cell cycle control in cancer. - Cell membrane molecules that regulate tumor growth rates and patterns of tumor growth. - Trop-regulated cell-cell adhesion in normal and tumorigenic cells. - Angiogenesis in tumors. Two additional units are to be announced. CONTROL OF HAEMOPOIESIS (Michael Mackey, Joseph Mahaffy and Jacques Belair) - Periodic Hematological Diseases: Pathology, Modeling, and Treatment (two units). - Peripheral Control of Red Blood Cell Production (two units). - Peripheral Control of White Blood Cell Production (two units). - Stem Cell Dynamics: Understanding Cyclical Neutropenia and Periodic Leukemia (two units). - Regulation of Platelet Production by Thrombopoietin (two units). CYTOMETRY AND PARAMETER ESTIMATION (S. Alberti, A. Bertuzzi, A. De Gaetano and L. Del Vecchio) - Basic flow cytometry. - Characterization of asynchronous exponential growth. - Models for the analysis of data from asynchronous growth. - Evaluation of cell cycle effects of drugs. - Proliferation markers and detection of cell death. - Gene expression analysis by flow cytometry and confocal microscopy. - CD45-driven identification of normal and leukemic cells in human bone marrow. - Basic geometry of parameter estimation for nonlinear models. - Fundamental results for least-squares and maximum likelihood estimators. - Curvature, confidence intervals and model choice. - Population parameter estimation for nonlinear models. CYTOSKELETON AND REGULATION OF CELL FUNCTION (Jany Vassy, Sophie Lelièvre, Michael Beil, Damien Schoevaert and Stéphanie Portet) - Tissue architecture and gene expression, study of tissue matrix in three-dimensional models of cell culture. - Cytoplasmic cytoskeleton as a link between cell environment and nucleus. - Non-chromatin structure of the nucleus or nuclear matrix, its interaction with chromatin structure and its role in the regulation of gene expression. - Automated image analysis of the cytoskeleton architecture. Methods and applications. - Image analysis of the cytoskeleton in cell movement. - Modelisation of the architecture of cytokeratin networks. ROUND-TABLE: the role of biomathematics in large biological research institutions and corresponding career openings for young biomathematicians. SECOND WEEK =========== STRUCTURED CELL POPULATIONS (Eva Sanchez, Ovide Arino, Tanya Kostova and Glenn Webb) - Asynchronous exponential growth and semigroup theory. Existence of steady-state distributions. Generalities on semigroup theory. Positive semigroups. - Size-density models.Syngle type models. Models with two compartments. Size-age density models. - Time continuous daughter cell models. Model with deterministic lifelength. Model with stochastic lifelength. - A short review of other linear structured cell population models. Comparison of approaches to modeling of cell population dynamics. - Introduction to nonlinear models. Unequal division. Selective regulation of cell population growth. - Structured population models of the blood cell production system. Chaotic behavior in maturity structured models. - Structured population models of limited proliferative capacity in dividing cell lines. Telomere fragment shortening on the ends of chromosomes. - Structured population models of tumor cord cell migration. Cell kinetics in the vascularized steady state. - Examples of Age- and Size- Structured Models in Cellular Biology. What does Numerical Solving mean? The Grid and the Step. - Interpolation, Quadratutures, Order of Approximation, the Error, Runge-Kutta Methods. Outline of Several Numerical Methods to Solve Age- and Size- Structured Models. First, second, high accuracy methods. MODELLING CANCER CHEMOTHERAPY (Zvia Agur and Andrzej Swierniak) - The use of mathematical models for understanding the cell cycle clock in mammalian cells and its crackdown in cancer. - Optimizing cell-cycle specific chemotherapy: insights gained from mathematics (two units). - Introduction to optimal control, controllability, observability. The Bellman principle of optimality. - Dynamic programming, application of dynamic programming to discrete- time systems, the discrete LQ problem. - Pontryagin maximum principle, application of the maximum principle to continuous LQ problems and bang-bang control. - Introduction to stochastic optimization (dynamic programming approach), LQG problem, problem with Markovian jumps JLQ. - Examples of applications in optimization of cancer therapy. Two additional units are to be announced. POPULATION GENETICS OF ORGANISMS AND CELLS (William Amos, Ranajit Chakraborty and Marek Kimmel) - Basic principles of genetics of diploid organisms: chromosomes, genes, alleles, DNA, segregation, and recombination. - Genetics of populations: mutation, genetic drift, selection. - Important loci systems: autosomal and sex-linked loci, mitochondrial DNA, repeat-DNA. - Genetics of unicellular organisms, somatic cells and organelles. - Estimation of relatedness of individuals. - Models of mutational processes: Markov Chain models, Infinite Allele and Infinite Site Model and Stepwise Mutation Model. - Wright-Fisher-Moran model of genetic drift. - Coalescence: the backward look at population genetics processes. Ancestral stochastic processes. Connection with branching processes. - Coalescence with mutations and demographic change. Relationship to dynamical systems. Population dynamic coded in DNA - Evolution of microsatellite loci: inference from data and connection with mathematical models (two units). - Dynamic mutations and trinucleotide-related diseases: Data and models. - Infinite Sites Model and mitochondria as molecular clocks. - Evolution of mitochondria in somatic cells: origins of heteroplasmy, mitochondrial diseases. One additional unit is to be announced. INVITED TALKS ============= - Sufficient conditions for non-existence of periodic solutions in some classes of delay differential equations (E. Beretta) - From a stochastic system of interacting individuals to a non linear diffusion continuous aggregation model. (V. Capasso) - The Conditional Neyman-Pearson Lemma and model choice (W.P. Coleman) - TBA (A. Goldbeter) - Chemotaxis and aggregation in the cellular slime mould (T. Hoefer) - Modelling age-structured populations (M. Iannelli) - Free boundary problems for solid tumor evolution (L. Preziosi) - Modelling Cell Populations Using Branching processes: Theory And Specific Applications (Z. Taib) LABORATORIES ============ - Experimental techniques in oncology and molecular biology: transfection (S. Alberti). - Cancer and chemotherapy in animal models (S. Caltagirone, A. Di Castelnuovo). - Electrophysiology and microdialysis in the study of the CNS (M. Di Mascio). - Production of transgenic mice by pronuclear microinjection of foreign DNA (C. Dossi). - Potassium channels studied in Xenopus Laevis oocytes (M.Pessia). - Regulation of cell-cycle, oncogenes and anti-oncogenes (A. Sala). - Measurement of cellular DNA content by flow citometry (P. Ubezio, N. Martelli). - Electron microscopy in cell biology (R. Weigert). ------------------------------------------------------------------ APPLICATION =========== Compile and return the following Application Form directly from the school's webpage, or by e-mail to the address biomath@tin.it The application form may also be sent in paper (mail or fax) to Andrea De Gaetano CNR - Centro Fisiopatologia Shock Laboratorio di Biomatematica UCSC - L.go A. Gemelli, 8 00168 Roma, Italia Fax: +39-06-3385446 Tel: +39-06-3385446 +39-06-30155389 +39-06-30154082 /********************************************************************\ * MATHEMATICS IN CELL PHYSIOLOGY AND PROLIFERATION * * SUMMER SCHOOL, TERMOLI, ITALY, 6-19 JUNE 1999 * * APPLICATION FORM * \********************************************************************/ GENERAL ======= ...................................................................... Surname, First Name, Title ...................................................................... Position ...................................................................... Institution ...................................................................... Address, Phone/Fax ...................................................................... Email (attention! will be used as the primary means of communication) ...................................................................... Main Area of Interest [ ] Biologist/Medical or [ ] Mathematician/Engineer/Physicist CONTRIBUTED PRESENTATION ======================== (Deadline if submitted: May 1, 1999. The application form may be sent without compiling this section) [ ] I am contributing a presentation ...................................................................... presentation title ...................................................................... presentation keywords (up to five) I am sending by mail[ ] or as e-mail attachment[ ] up to five A4 pages of presentation notes FINANCIAL SUPPORT ================= If asking financial support, please state briefly the motivation. ...................................................................... ...................................................................... ...................................................................... ...................................................................... ...................................................................... ----------------------------------------------------------------------