Kinetic modeling of pharmacokinetics/pharmacodynamics (PK/PD)

Pharmacokinetic modeling is used to assess the drug concentration in body fluids and tissues over time resulting from administration of a certain drug dose. Modeling enables to estimate concentration time courses in different tissues even having limited amount of experimental data. The dose can be optimized depending on the means of administration and other parameters.

Knowing the concentration time courses the drug effect (pharmacodynamics) can be assessed establishing the effect time courses resulting from a drug dose.

We have experience in pharmacokinetic modeling of rat and human and plan to extend the research towards pharmacodynamics studies.

Our main modeling tool is the software COPASI. We have used COPASI alone and in combination with COPASI wrapper SpaceScanner to manage parallel optimisation runs of global stochastic optimisation methods. 

Boolean modeling of signaling and protein-protein interaction networks

Signaling and protein-protein interaction (PPI) networks differ from metabolic processes in many aspects. One can not relay there on mass conservation constraint. At the same time Boolean type of modeling gives effective modeling tool limiting the states just by active (=1) or inactive (=0) states. Boolean modeling can be combined also with kinetic modeling technologies whenever sufficient amount of details is available.

PPI networks of actin polymerisation in humans and signaling networks in plants are addressed by our group so far.

We use GinSim, CellNetAnalyzer and Cellcollective software tools.

Kinetic modeling and optimisation

We are developing and optimising kinetic models of metabolism, pharmacokinetics and signaling. Other types of processes can be addressed depending on the amount of the available information.
Our particular strength is the experience in use of global stochastic optimisation methods in parameter estimation and optimisation tasks. In both cases we are implementing different types of constraints to improve the credibility of results.

Our main modeling tool is the software COPASI. We have used COPASI alone and in combination with COPASI wrapper SpaceScanner to manage parallel optimisation runs of global stochastic optimisation methods. 

 

 

 

Stoichiometric modeling of metabolism

Stoichiometric modeling approach can be used for analysis of feasible steady states (metabolite concentrations are not changing in time) and minimally need information just about reaction stoichiometry. Additional constraints like lower and upper bounds of fluxes, reaction directionality and others can make the model predictions more accurate. Small amount necessary of information per reaction enable development of large models. At the same time the disadvantage is that stoichiometric models can not be used to simulate any changes in time and can not calculate metabolite concentrations.

We have been stoichiometrically modeling metabolism of very different organisms:

  • bacteria Zymomonas mobilis and Escherichia coli,
  • unconventional yeast Kluyveromyces marxianus,
  • plant Arabidopsis thaliana,
  • human metabolism.

We see high potential of genome scale modeling application in Personalised Mecicine

We have used several software platforms COBRA, ScrumPy and COBRApy.

We have developed some software for stoichiometric modeling like Paint4Net for COBRA, AltFluxes for COBRA.

Synthetic Biology

(leader Professor E.Stalidzans)

Synthetic Biology (SynBio) aims to modify existing organisms or create new ones using engineering approach. Registry of Standard Biological Parts is one of consequences of engineering approach used deveolping technical systems. Now stadartized parts can be used in biology.

SynBio holds a number of promises to secure or improve quality of life. On the other hand there are potential and perceived risks due to deliberate or accidental damage. In addition, ethical issues related to the nature of living beings are arising. In order to ensure the successful development of this new scientific field it is necessary to gather information about its risks and to devise adequate bio-safety strategies to minimize them.

Our group deals mostly with model based design of new strains for biotechnological use.

Computational methods of Systems Biology

Systems Biology (SysBio) comes as next level of our modelling activities indicated in other topics of research interest. We see there enormous potential for development where our skills can be applied in global research topics. Application of control theory looking at complexity of living systems, development of SysBio dedicated software, development of different IT support are directions where we have high potential.

Currently we study the BioModels database using the new version of COPASI. Currently we investigate recognition of control networks in molecular processes focusing on control loops, their interaction to get closer to the miracle of stability of a cell.

Another topic of research is the process of glycolisis because of rich amount of data. We are currently looking for possibilities to extract more knowledge of existing data.