1. Lecture 3: Models of gene regulation

2. DNA Replication RNA Protein TranscriptionTranslation

3. Bacterial growth on sugars How does the cell know which enzymes to express?

4. hours [conc.] glucose lactose Bacterial growth on two substrates: Two things to notice: 1.Glucose metabolized before lactose 2.Lag between glucose and lactose growth phases [Monod, Thesis 1942]

5. Monod realized this was operating like a genetic “switch” –Genes required for lactose metabolism turned off in presence of glucose –But turned on in absence of glucose and presence of lactose Input/Ouput relation:Lactose +- Glucose +-- -+-

6. crp lacI lacZ lacYlacA Three main components: 1.Genes: encode protein sequence 2.Promoters: RNAP binding sites 3.Operators: Transcription factor binding sites lacZ The lac Operon

7. The Prokaryotic Promoter NNNNTTGACANNNNNNNNNNNNNNNNNTATAATNNN -35-10 17 bp The promoter is a binding site for the protein RNA polymerase, responsible for transcription

8. DNA Replication RNA Protein TranscriptionTranslation Transcription factor (protein that repress or activate) Rate usually depends on transcription factor

9. Gene regulation functions ( rate of transcription as a function of factors or regulators)

10. Dynamics: single regulated gene

11. Single regulated gene ( U= protein conc or expression level )

12. Graphical analysis of steady states and stability

13. Mutual inhibition network of transcription factors R1 R2 After eliminating the mRNA variables

14. Nullclines

15. Phase plane

16. Domain of bistability For both genes: maximal expression level should be able to repress the repressor HW: Sketch the phase planes for the 4 different regimes in the model Expression of both R 1 off

18. Mutual repression circuit

19. Toggling the switch (transients: IPTG affects R 1, temp affects R 2 )

20. Parametric dependence of steady states (GFP- flourescence protein)

21. Parametric dependence of steady states individual cells