1. Projects in need of doing Rui Alves

2. Metabolic Reconstruction Rui Alves

3. To do Literature analysis –Semi done –Needs to implement FREQUENCY ANALYSIS CO-OCCURENCE ANALYSIS A GOOD DATA BASE STRUCTURE TO KEEP TRACK OF PREVIOUS SEARCHES AND USE THEM A GOOD VISUALIZATION TOOL

4. You would learn Literature analysis –PHP –APACHE –MAYBE JAVA AND C

5. To Do Phylogenetic analysis –60% done –Needs to improve the database structure –Needs to implement a web front to connect the database to a browser

6. You would learn Literature analysis –PHP –APACHE –HTML –MYSQL

7. To Do MODELLING & DOCKING –IMPLEMENT A METASEARCH TOOLS TO USE EXISTING MODELLING SERVERS –SAME FOR DOCKING –IMPLEMENT IN HOUSE WAY OF RUNNING ROBETTA –WEB INTERFACE

8. You would learn Literature analysis –PHP –APACHE –HTML –C

9. To Do INTEGRATIVE ARCHITECTURE –DESIGN ARCHITECTURE TO INTEGRATE ALL DATA

10. You would learn Literature analysis –PHP –APACHE –HTML –C

11. To Do BIOLOGICAL APPLICATION, ALLWAYS

12. REWARDS CO-AUTORSHIP IN PAPERS DESCRIBING THE WORK THERE MAY BE SOME MONEY FOR ONE PART TIME JOB FOR A FEW MONTHS, DEPENDING ON HOW THE MINISTRY ALLOWS THE ADMINISTRATION OF THE PROJECTS

13. Design Principles in Signal Transduction Rui Alves

14. To Do Compare MAPK pathways to TCS Compare different types of TCS Compare different types of MAPKS

15. TCS MAPK

17. You would learn MATHEMATICA MATHEMATICAL MODELLING

18. REWARDS CO-AUTORSHIP IN PAPERS DESCRIBING THE WORK

19. Modeling the life cycle of the lac operon Rui Alves

20. To Do Start working with stochastica approximations to analyze demand theory not only in gene expression but also in protein modules

21. You would learn MATHEMATICA MATHEMATICAL MODELLING Mathematically Controlled Comparisons Theoretical ecology

22. REWARDS CO-AUTORSHIP IN PAPERS DESCRIBING THE WORK Possibility of going abroad if funding can be secured

23. The lac operon lacZ (3510)lacY (780)lacA (825)PO lacI (1040)  -Gal PermeaseAcetylaseInhibitor lacI CAP RNA Pol

24. Maintenance of the lac operon as a function of life style Can one understand, quantitatively, which are the boundaries for selection of the lac operon so that bacteria do not lose this operon through random drift?

25. The lac operon lacZ (3510)lacY (780)lacA (825)PO lacI (1040)  -Gal PermeaseAcetylaseInhibitor lacI Mike has done the analysis, with the simplifying assumptions that no glucose was ever in the medium (i.e. CAP is always on) and considering only the regulator mutants and building and analyzing a model of bacterial growth

26. Determining the mutant to wild type ratios as a function of time

27. Bacteria Cycle between environments with high (H) and low (L) Lac

28. Parameter values are a function of the environment and of the genotype

29. Selection boundaries for the lac operon Promoter Ratio= 0.001 Regulator Ratio= 0.001 Selection for inhibitor and promoter elements

30. The lac operon lacZ (3510)lacY (780)lacA (825)PO lacI (1040)  -Gal PermeaseAcetylaseInhibitor lacI CAP RNA Pol XwXw X Z- X Y- X I- X CAP- X P- X P+

31. The lac operon: Selecting an up-promoter lacZ (3510)lacY (780)lacA (825)PO lacI (1040)  -Gal PermeaseAcetylaseInhibitor lacI CAP RNA Pol XwXw X Z- X Y- X I- X CAP- X P- X P+

32. Gain of function promoter mutant Stronger promoter selected

33. The lac operon:Selecting a down-promoter lacZ (3510)lacY (780)lacA (825)PO lacI (1040)  -Gal PermeaseAcetylaseInhibitor lacI CAP RNA Pol XwXw X Z- X Y- X I- X CAP- X P- X P+

34. Loss of function promoter mutant Stronger promoter selected Weaker promoter selected Maintenance of current promoter

35. The lac operon: Selecting for less efficient lacZ lacZ (3510)lacY (780)lacA (825)PO lacI (1040)  -Gal PermeaseAcetylaseInhibitor lacI CAP RNA Pol XwXw X Z- X Y- X I- X CAP- X P- X P+

36. Loss of function  -Gal Weaker galactosidase selected Maintenance of current  -Gal plus promoter

37. lacZ (3510)lacY (780)lacA (825)PO lacI (1040)  -Gal PermeaseAcetylaseInhibitor lacI CAP RNA Pol XwXw X Z- X Y- X I- X CAP- X P- X P+ The lac operon: Selecting for less efficient lacY

38. Loss of permease function mutant Weaker permease selected Maintenance of current permease plus  -Gal plus promoter

39. lacZ (3510)lacY (780)lacA (825)PO lacI (1040)  -Gal PermeaseAcetylaseInhibitor lacI CAP RNA Pol XwXw X Z- X Y- X I- X CAP- X P- X P+ The lac operon: Selecting for less efficient lacI

40. Loss of function inhibitor Maintenance of current repressor protein plus permease plus  -Gal plus promoter Weaker repressor selected

41. lacZ (3510)lacY (780)lacA (825)PO lacI (1040)  -Gal PermeaseAcetylaseInhibitor lacI CAP RNA Pol XwXw X Z- X Y- X I- X CAP- X P- X P+ The lac operon: Selecting for less efficient CAP

42. Loss of function activator Demand for activator OR absence of Glucose If D~<2x10 -4, activator is lost for this particular circuit

43. Connecting Lac operon demand regulated by Glu and Lac Demand for LacI Demand for CAP

44. Connecting Lac operon demand regulated by Glu and Lac Demand for LacI Demand for CAP

45. Connecting Lac operon demand regulated by Glu and Lac Demand for LacI Demand for CAP

46. Connecting Lac operon demand regulated by Glu and Lac Demand for LacI Demand for CAP

47. Connecting Lac operon demand regulated by Glu and Lac Demand for LacI Demand for CAP

48. Connecting Lac operon demand regulated by Glu and Lac Demand for LacI Demand for CAP

49. Connecting Glu and Lac demand XwXw X Z- X Y- X I- X CAP- X P- X P+

50. Bacteria Cycle between environments with high and low Lac and high and low Glu 4 fractions of the cycle

51. The words: Demand for LacI Demand for CAP Highest extend of selection for this type of demand cycle ~99.2%0.8% ~0.005% ~0.07%

52. HL,HH,HL,LL

58. HL,HH,LH,LL

60. HL,LL,LH,LL

62. HH,HL,LL,LH

64. Sensitivity Analysis

66. Lambda-cro

67. The lac operon High LactoseLow Lactose High Gluco se Low Gluco se High Gluco se Low Gluco se