Introduction to Systems Biology

Transcription

1

2 Introduction to Systems Biology References: Watson s Molecular Biology of the Gene, Chapter 22 Alberts Molecular Biology of the Cell, Chapter 7 Yousof Gheisari ygheisari@med.mui.ac.ir

3 Why is this picture chosen for a molecular biology textbook? 3

4 Technological advances have transformed the nature of molecular biology The ability to identify and characterize every component of a process provides the opportunity for a new line of inquiry: what are the underlying design principles? Towards a proteome-scale map of the human protein-protein interaction network. Nature Oct 20;437(7062):

5 Noorbakhsh et al, Trends in Neuroscience 2009

6 Ref: He JC at al, Kidney Int Jan;81(1):22-39.

7 Ref: He JC at al, Kidney Int Jan;81(1):22-39.

8 Technological advances have transformed the nature of molecular biology Classical biology Genetics Sequence Expression Protein chemistry Metabolic studies Lipid biology Systems biology Genomics Structural genomics Functional genomics Proteomics Metabolomics Lipidomics Hypothesis-driven research Discovery-driven research

9 Cell is much more complex than previously beleived Mol Syst Biol : msb Apr. 18,

10 The aim of systems biology is to describe complex biological interactions An emerging approach (>year 2000) Systems biology is a biology-based interdisciplinary field of study that focuses on complex interactions within biological systems, using a more holistic approach. The objective of Systems Biology is to describe the properties of the web of interactions that govern the workings of living things and to do so in a manner that is quantitative and predictive

11 Systems Biology entails a new way of thinking "Systems biology...is about putting together rather than taking apart, integration rather than reduction. It requires that we develop ways of thinking about integration that are as rigorous as our reductionist programs, but different...it means changing our philosophy, in the full sense of the term" (Denis Noble).

12 Elephant in the Dark Room!

13 The systems biology strategy Biochimica et Biophysica Acta 1796 (2009)

14 Mathematical modeling has been used in industry for several years 27

15 There are two different approaches in systems biology Bioorganic & Medicinal Chemistry Letters 23 (2013)

16 Top-Down Approach Bioorganic & Medicinal Chemistry Letters 23 (2013)

17 Bottom-Up Approach Individual components are assembled into a network with the goal to simulate the dynamic properties. Ordinary differential equation (ODE)-based modelling is a common approach 30

18 Bottom-Up Approach Good Models need to provide answers or generate hypotheses that can not be intuitively obtained. Purpose of Modeling: Prediction accounting of systems with large data sets. Predictions should be Non-obvious and need computation. Predictions should be Experimentally verified.

19 How to make a realistic model Do not oversimplify; Build model with enough details (different isoforms of receptor, ) Use available experimental data to have reasonable (realistic) parameters. Do not tweak (change) the parametrs so that simulations show a desired behavior.

20 Different views of the AKT pathway Biochimica et Biophysica Acta 1796 (2009)

21

22 Regulatory circuits can be described as simple networks consisting of nodes and edges A cell can use various network motifs as miniature logic devices to process information in surprisingly sophisticated ways.

23 The simple devices are combined in eukaryotic cells to create complex circuits The complex circuit that specifies a portion of the developing sea urchin embryo

24 Network motifs are patterns that recur much more frequently Milo R, et al. Science. 2002;298(5594):824-7.

25 Network motifs are patterns that recur much more frequently Milo R, et al. Science. 2002;298(5594):824-7.

26

27

28