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Developing quantitative methods for estimating birth and death rates of immune cells using CFSE label

Cel

The regulation of cell division and survival is central to immune regulation, and traditionally the analysis of these processes has been qualitative and descriptive. Recently developed techniques that allow one to follow antigen-specific T and B cells labe led with the dye CFSE over time have stimulated renewed interest in lymphocyte kinetics. Despite the widespread use of this labeling technique in immunology, the proper interpretation of labeling data is difficult and requires analysis with appropriate ma thematical models. We propose to develop efficient mathematical methods to quantify the population kinetics of lymphocytes during immune responses based on the CFSE labeling technique. For this, we plan to use the published data and are collaborating with the laboratory of Dr. Philip D. Hodgkin (Walter and Eliza Hall Institute of Medical Research, Australia), the well-known expert in CFSE labeling technique, to obtain unpublished data on the dynamics of CFSE-labeled T and B lymphocytes in vitro and in viv o. These data will be analyzed using a series of mathematical models with increased levels of complexity. These different models will be used against the data to determine how well the models can describe the data and whether such models are biologicall y realistic. The main theoretical challenge here is to develop mathematical models that are both realistic and contain minimum parameters that can be reliably estimated from the labeling data. The proposed research will allow the coordinator (VVG) to imp rove his skills in developing mathematical models of immune cell dynamics, in application of these models to experimental data, and in learning different techniques of estimation of model parameters. The proposed research will likely result in development of a group of researchers in EU with expertise in the several areas of theoretical immunology including the analysis of data obtained from the dynamics of CFSE labeled lymphocytes.

Zaproszenie do składania wniosków

FP6-2004-MOBILITY-7
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UNIVERSITEIT UTRECHT
Wkład UE
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Heidelberglaan 8
UTRECHT
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