CDS 270-4, 2010: Bio-Control

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Spring 2010

NOTE: The Friday lectures will include discussing a paper related to the week topic. Papers will be announced about a week prior to the discussion.

Course Objectives: Biology and Control Theory

Feedback loops, which are ubiquitous in engineered systems, play a fundamental role in most biological processes. The survival of any organism strictly depends on its ability to sense and react to changes in its environment. Like electrical and mechanical control systems, cells have the molecular gear necessary to sense, compute and actuate. What are the theoretical and experimental tools available to understand the regulatory circuitry in biochemical systems? This course will provide students with an organized overview of research work between control theory and molecular biology.

The first part of the class will be dedicated to modeling, identification and control-theoretic methods for the analysis of biological networks, following a systems biology perspective. The second part of the class will instead focus on design principles, and the challenges related to constructing biological pathways. Can we build modular and robust networks satisfying performance specifications? This fascinating field offers a wide range of challenging open questions, which the students will be encouraged to critically discuss.

Course Schedule

Week Date Lecture Topic Papers considered in class BioControl Journal Club
1 Introduction, Modeling biological systems
29 March (M) Course overview and objectives, layers of control of gene expression. Slides Syllabus NA
2 April (F) Modeling: Ordinary Differential Equations. Slides Review on modeling genetic regulatory networks and Modeling the trp operon Model-based redesign of transcriptional networks
2 Deterministic and stochastic modeling
6 April (T) CDS methods for dynamic performance and periodic behaviors. The case of Negative Auto-Regulation. Slides Detection of multistability, bifurcations and hysteresis in biological positive-feedback systems , Negative Autoregulation Speeds the Response Times of Transcription Networks NA
9 April (F) Modeling: Stochastic methods, Gillespie algorithm. Slides Gillespie's fundamental paper Defining bifurcations in stochastic systems
3 System identification in biology
13 April (T) Overview of system identification methods. Slides NA
16 April (F) Experimental approaches to identification of biological networks Slides Using noise for parameter identification, Identification of network connectivity, Experimental identification of network topologies, Using dynamic correlation to reveal regulatory activity NA
4 Theory of Chemical Reaction Networks
20 April (T) General introduction and examples. Structural properties of CRNs. Slides M. Feinberg, original notes , H. Othmer, Theory of Complex Reaction Networks NA
23 April (F) Proof of the Deficiency Zero Theorem Slides Chemical Reaction Network Theory for In Silico Biologists Structural Sources of Robustness in Biochemical Reaction Networks, Shinar & Feinberg
5 Monotone systems
27 April (T) Definitions and basic theorems Slides Monotone Control Systems NA
30 April (F) Predicting oscillations; monotonicity in CRNs. The MAPK pathway. Slides, Slides Oscillations in I/O Monotone Systems Under Negative FeedbackOscillations in I/O Monotone Systems Under Negative Feedback Graph-theoretic characterizations of monotonicity of chemical networks in reaction coordinates.
6 Synthetic biology: design principles
4 May (T) Design of molecular control systems and demand for gene expression Slides Large-scale metabolic network organization, Genetic modules design principles NA
7 May (F) Network motifs, structural and dynamical properties, Slides Review on network motifs, theory and experiments NA
7 Synthetic biology: design principles
14 May (F) RNA-based control and ultrasensitivity Slides RNA synthetic biology, review, sRNA-based regulation, Ultrasensitive response in protein interactions
8 Robustness
18 May (T) Introduction: robustness in control theory vs biology Slides Review on robustness of cellular functions, Heat shock response in E. coli, Model checking for robust biological networks NA
21 May (F) Chemotaxis: robust perfect adaptation Slides
8 Modularity in control theory and biology
26 May (W) Time-scale separation principle and dynamical systems approaches to modularity NA
28 May (F) Modularity in experimental biology

Course Administration

This course is a special topics course in which the lecture material has been prepared by a senior graduate student. The class is P/F only and there is no required homework and no midterm or final exam. Students will be required to work on an individual or team course project.

Course Project

Project proposals are due at 5pm on the last day of the Midterm examination period (May 4) and are due by 5pm on the last day of the final examination period (June 7). Project theme: select a cellular regulatory mechanism, define a list of important features of the system, come up with a modeling framework and carry out an analysis of its properties (e.g. stability, robustness, modularity...).