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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 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
You would learn • Literature analysis • PHP • APACHE • MAYBE JAVA AND C
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
You would learn • Literature analysis • PHP • APACHE • HTML • MYSQL
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
You would learn • Literature analysis • PHP • APACHE • HTML • C
To Do • INTEGRATIVE ARCHITECTURE • DESIGN ARCHITECTURE TO INTEGRATE ALL DATA
You would learn • Literature analysis • PHP • APACHE • HTML • C
To Do • BIOLOGICAL APPLICATION, ALLWAYS
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
Design Principles in Signal Transduction Rui Alves
To Do • Compare MAPK pathways to TCS • Compare different types of TCS • Compare different types of MAPKS
TCS MAPK
You would learn • MATHEMATICA • MATHEMATICAL MODELLING
REWARDS • CO-AUTORSHIP IN PAPERS DESCRIBING THE WORK
To Do • Start working with stochastica approximations to analyze demand theory not only in gene expression but also in protein modules
You would learn • MATHEMATICA • MATHEMATICAL MODELLING • Mathematically Controlled Comparisons • Theoretical ecology
REWARDS • CO-AUTORSHIP IN PAPERS DESCRIBING THE WORK • Possibility of going abroad if funding can be secured
The lac operon lacI (1040) PO lacZ (3510) lacY (780) lacA (825) Inhibitor b-Gal Permease Acetylase lacI CAP RNAPol
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?
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
Determining the mutant to wild type ratios as a function of time
Bacteria Cycle between environments with high (H) and low (L) Lac
Parameter values are a function of the environment and of the genotype
Selection boundaries for the lac operon Regulator Ratio= 0.001 Promoter Ratio= 0.001 Selection for inhibitor and promoter elements
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
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+
Gain of function promoter mutant Stronger promoter selected
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+
Loss of function promoter mutant Stronger promoter selected Weaker promoter selected Maintenance of current promoter
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+
Loss of function b-Gal Maintenance of current b-Gal plus promoter Weaker galactosidase selected
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+
Loss of permease function mutant Maintenance of current permease plus b-Gal plus promoter Weaker permease selected
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+
Loss of function inhibitor Maintenance of current repressor protein plus permease plus b-Gal plus promoter Weaker repressor selected
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+
Loss of function activator If D~<2x10-4, activator is lost for this particular circuit Demand for activator OR absence of Glucose
Demand for LacI Demand for CAP Connecting Lac operon demand regulated by Glu and Lac
Demand for LacI Demand for CAP Connecting Lac operon demand regulated by Glu and Lac
Demand for LacI Demand for CAP Connecting Lac operon demand regulated by Glu and Lac
Demand for LacI Demand for CAP Connecting Lac operon demand regulated by Glu and Lac
Demand for LacI Demand for CAP Connecting Lac operon demand regulated by Glu and Lac
Demand for LacI Demand for CAP Connecting Lac operon demand regulated by Glu and Lac
Connecting Glu and Lac demand XZ- XCAP- Xw XP- XP+ XY- XI-
Bacteria Cycle between environments with high and low Lac and high and low Glu 4 fractions of the cycle