Projectdetails

For decades immunologists have tried to estimate the typical proliferation and death rates of lymphocytes. Even though these rates are often regarded textbook immunology, estimates easily vary by more than 100-fold. Nevertheless, these turnover rates are

a key factor in our understanding of fundamental immunological processes, varying from immunological memory, and maintenance of lymphocyte diversity, to the consequences of thymus involution with age. Thanks to recent experimental advances, including the application of stable-isotope labelling to measure cells that undergo proliferation, the time is now ripe to determine these rates of lymphocyte turnover. However, proper interpretation of the experimental data hinges upon the use of mathematical models; without such models, labelling curves remain merely descriptive and do not yield the quantitative turnover parameters that are needed. Moreover, mathematical modelling helps to obtain insights into the complicated dynamical processes underlying the functioning of the immune system.

Unfortunately, there is still an enormous gap between immunologists and mathematicians, which hampers a potentially fruitful synergy between the two fields of research. My aim is to bridge this gap by consolidating a truly interdisciplinary approach in which mathematical analyses are performed within the context of an experimental immunology group. Experimental data will be interpreted by newly derived mathematical models, and the insights obtained from the mathematical models will lead to new hypotheses to be tested experimentally. This interdisciplinary approach will be used to determine the typical rates of cell death and proliferation of different lymphocyte populations, to study the contribution of the thymus to the maintenance of the peripheral T cell pool at different ages, and to investigate the population dynamical ?rules? of lymphocytes. On a longer time scale, this grant will enable me to establish a permanent line of research that changes the traditionally rather qualitative field of immunology into a more quantitative science.