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

Modeling the life cycle of the lac operon Rui Alves

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 lacZ (3510)lacY (780)lacA (825)PO lacI (1040)  -Gal PermeaseAcetylaseInhibitor lacI CAP RNA Pol

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 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

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 Promoter Ratio= Regulator Ratio= Selection for inhibitor and promoter elements

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+

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+

Gain of function promoter mutant Stronger promoter selected

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+

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

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+

Loss of function  -Gal Weaker galactosidase selected Maintenance of current  -Gal plus 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+ The lac operon: Selecting for less efficient lacY

Loss of permease function mutant Weaker permease selected Maintenance of current permease plus  -Gal plus 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+ The lac operon: Selecting for less efficient lacI

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

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

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

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 Demand for LacI Demand for CAP

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

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

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%

HL,HH,HL,LL

HL,HH,LH,LL

HL,LL,LH,LL

HH,HL,LL,LH

Sensitivity Analysis

Lambda-cro

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