Classes: Duration of the school is two weeks, including 11 days of classes, Monday through Friday, plus the intervening Saturday morning. Each day there will be 8 or 9 lecture units of 40 min by the staff and by invited speakers. Afternoon practice and exercise sessions will be conducted three times a week. Participants will also have the opportunity to deliver their own presentations. Two afternoon sessions per week will be conducted 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 voiced in discussions with the Mario Negri researchers, as well as to show actual laboratory experiments from which data arise.
The language of the school is English. Most school activities will take place in the same hotel where rooms and meals are provided. Most of the lecture sequences will be completed in a single week, biological subjects being treated in the first week and more mathematical subjects being treated in the second week.
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
- 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. - Mechanisms of activation of oncogenes and tumor suppressor genes in human neoplasia.
- 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).
- 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.
- 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.
- 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.
- 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.
- 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.
- From a stochastic system of interacting individuals to a non linear diffusion continuous aggregation model. (V. Capasso, D. Morale)
- The Conditional Neyman-Pearson Lemma and model choice (W.P. Coleman)
- 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)
- 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).