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Projects in need of doing

Projects in need of doing. Rui Alves. Metabolic Reconstruction. Rui Alves. 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.

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Projects in need of doing

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  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

  16. You would learn • MATHEMATICA • MATHEMATICAL MODELLING

  17. REWARDS • CO-AUTORSHIP IN PAPERS DESCRIBING THE WORK

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

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

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

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

  22. The lac operon lacI (1040) PO lacZ (3510) lacY (780) lacA (825) Inhibitor b-Gal Permease Acetylase lacI CAP RNAPol

  23. 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?

  24. The lac operon lacI (1040) PO lacZ (3510) lacY (780) lacA (825) Inhibitor b-Gal Permease Acetylase 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

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

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

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

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

  29. XCAP- XZ- XP- Xw XY- XI- XP+ The lac operon lacI (1040) PO lacZ (3510) lacY (780) lacA (825) Inhibitor b-Gal Permease Acetylase lacI RNAPol CAP

  30. The lac operon: Selecting an up-promoter lacI (1040) PO lacZ (3510) lacY (780) lacA (825) Inhibitor b-Gal Permease Acetylase lacI RNAPol CAP XCAP- XZ- XP- Xw XY- XI- XP+

  31. Gain of function promoter mutant Stronger promoter selected

  32. The lac operon:Selecting a down-promoter lacI (1040) PO lacZ (3510) lacY (780) lacA (825) Inhibitor b-Gal Permease Acetylase lacI RNAPol CAP XCAP- XZ- XP- Xw XY- XI- XP+

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

  34. The lac operon: Selecting for less efficient lacZ lacI (1040) PO lacZ (3510) lacY (780) lacA (825) Inhibitor b-Gal Permease Acetylase lacI RNAPol CAP XCAP- XZ- XP- Xw XY- XI- XP+

  35. Loss of function b-Gal Maintenance of current b-Gal plus promoter Weaker galactosidase selected

  36. The lac operon: Selecting for less efficient lacY lacI (1040) PO lacZ (3510) lacY (780) lacA (825) Inhibitor b-Gal Permease Acetylase lacI RNAPol CAP XCAP- XZ- XP- Xw XY- XI- XP+

  37. Loss of permease function mutant Maintenance of current permease plus b-Gal plus promoter Weaker permease selected

  38. The lac operon: Selecting for less efficient lacI lacI (1040) PO lacZ (3510) lacY (780) lacA (825) Inhibitor b-Gal Permease Acetylase lacI RNAPol CAP XCAP- XZ- XP- Xw XY- XI- XP+

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

  40. The lac operon: Selecting for less efficient CAP lacI (1040) PO lacZ (3510) lacY (780) lacA (825) Inhibitor b-Gal Permease Acetylase lacI RNAPol CAP XCAP- XZ- XP- Xw XY- XI- XP+

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

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

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

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

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

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

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

  48. Connecting Glu and Lac demand XZ- XCAP- Xw XP- XP+ XY- XI-

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

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