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Gene Regulatory Networks And Their Dynamics Model For Tumor Treatment

Posted on:2009-06-06Degree:DoctorType:Dissertation
Country:ChinaCandidate:J P QiFull Text:PDF
GTID:1114360242472700Subject:Pattern Recognition and Intelligent Systems
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Life is one of the most complicated system.Researchers in the fields of information and control are trying to study these organisms as a new kind of the complex system and intelligent system.All kinds of genes storing life information prompt the evolement of life through a complex network system,a gene regulatory network.The researches of the gene regulatory network are expetcted to discover the funtions and behavior of genome through systematic point of view,explain the complicated life processes at gene level in detail,and combine tightly together with the interprets at molecule level,and subsequently approach the targets for systematically explaining the cellular functions,life behaviours,and the mechanisms of illness and their therapy.As one of the complex biological system,tumor might be considered as one of the complicated network system.In this study,according to the recent biology studies related with tumor,we have made the scientific researches mainly on the modeling of gene regulatory network and their kinetics based on P53 and MDM2 genes and their signal pathways etc.The innovatitive research contributions mainly include the following contents:Improving the notional mode of P53 gene regluatory networkBased on the existing researches,we improved the notional model of P53 gene regulatory network.We cut out the redundant nodes and their regulatory pathways, and add more vital elements related tightly with tumor into our model according to the latest biology studies.Proposing a model of P53 gene regulatory network under DNA damageBased on the improved notional model,we propsed a model of P53 gene regulatory network under DNA damage,and investigated the complicated interactions and regulating kinetics among P53 genes and their signal pathways in cellular responding DNA damage.We simulated the dynamic processes of cellular self-defense mechanisms in response to the acute stimulations and genome stresses.Proposing a model of P53 gene regulatory network under continuous Ion Radiation(IR)According to the latest biology researches,we firstly proposed a model of P53 gene regulatory network under continuous IR.Under continous acute radiation,we implemented the modules of DNA damage generating and their repair,ATM activating,and P53-MDM2 feedback looper.Investigaing the abilities of cellular responding DNA damage under different IRWe improved the model of model of P53 gene regulatory network under continuous IR by adding much more elements related cellular response and network regulation.Under different IR dose domains,we realized the complicated kinentcis of cellular response DNA damage.Meanwhile,we analyzed the capabilities of cellular respons in fighting against different IR dose domains,and further investigate the self-defense mechanisms under complex circumstances. Proposing a model of P53 stress response network under radiotherapy Based on the latest biomedical researches,we proposed a model of P53 stress response network under radiotherapy,adding Oncogenes,ARE,Toxins into this model.Under continous radiation,we simulated the processes of genome damage generating,repairing and transducting,ATM and ARF activating,P53-MDM2 feedback regulating,as well as the toxins eliminating.Investigating the analyse and prediction of the cellular responding radiotherapy under different IR dose domainsWe improved the model of P53 stress response network under radiotherapy, including the cooperated activation of ATM and ARF,and the feedback looper formed by P53 and MDM2.Meanwhile,we simulated the whole process of tumor therapy under continuous IR,and further analyed the capabilities of cellular responding under different radiation time and different IR dose domains,further predicted the outcomes of tumor radiotherapy as well.In this research,we aimed to investigate the complicated regulating relationships among genes and their signal pathways related tightly with tumor therapy based on the modelling of gene regulatory network and their kinetics,build the dynamic model of cellular responding tumor therapy at sigle cell level,and to provide a theoretic framwork and simulating platform for the studies of tumor therapy further.Our researches can not only try to explain the complicated regulations among genes and their signal pathways,but also analy and predict the capabilities of cellular responding DNA damage under different circumstances.By multi-point of view,we can make a simplification for the complex process of tumor radiotherapy,and provide a novel way for theoretical research on modeling and simulating the tumor therapy.
Keywords/Search Tags:System biology, Gene regulatory network, P53, Tumor therapy, Ion Radiation, DNA damage, Oscillation, systematic modeling
PDF Full Text Request
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