Lent 2010 MPhil course \\\'Network biology\\\' - lecture 1

1. Perturbations and phenotypes - an introduction - Network Biology - lecture 1

5. Breaking the system DNA mRNA Protein RNAi Knockout Drugs Small molecules Stress SNPs natural variation

9. Science 1999

10. Evidence for network redundancy Fitness of single mutant (relative to wild-type cell) Fitness of yeast deletion mutants (~6000 different gene-level perturbations) 1800 1600 1400 1200 1000 800 600 400 200 0 Winzeler EA et al Science 1999 { ~80% can be independently deleted with no severe fitness defect!

11. Nature Reviews Genetics 2008

12. RNAi screens Boutros and Ahringer (2008)

13. Phenotype: pathway activity Cell membrane Receptors A- B- C-

14. Phenotype: organism morphology Boutros and Ahringer, Nat Rev 2008

15. Phenotype: cell morphology Boutros and Ahringer, Nat Rev 2008

16. Phenotype: global gene expression A- B- C- All the genes in the genome Transcriptional phenotypes by microarrays A- B- C- … … …

17. High-dimensional phenotypes by microscopy or molecular profiling Low-dimensional phenotypes A- Time Size

18. Phenotyping produces partslists Keith Haring, Untitled , 1986 Urs Wehrli, Tidying Up Art , 2003

21. Boutros, Bras, Huber 2006

22. Boutros, Bras, Huber 2006

23. Boutros and Ahringer 2008

25. Perturbations can have off-target effects www.dharmacon.com: Tech Report: Off-target effects: Disturbing the silence of RNAi Echeverri et al, Nature Methods 2006

28. Phenotypes give only limited information of cellular networks

29. .. even molecular phenotypes Model DNA mRNA Protein A B C D E

34. Network Biology - lecture 1 Questions ?