Pyruvate dehydrogenase E2 complex

Benedict Seddon group project:

Mathematical modelling of homeostatic responses

In order to understand how the integration of multiple environmental signals controls homeostatic T cell responses in vivo, it is becoming increasingly important to be able to precisely quantify the survival and proliferative events involved. Complex cellular behaviours are often governed by relatively simple set of biological parameters such as frequency and rate of cell division. We therefore employed a mathematical modelling approach to investigate the programme of cell division that takes place in lymphopenic conditions. While cognate TCR interactions induce a programme of cellular division and differentiation by responding T cells, stimulation by spMHC complexes in lymphopenic conditions induces a slower burst of divisions that may or may not be accompanied by effector differentiation. Although both responses are TCR dependent, it is not known whether they represent distinct programs of cell cycle control. We therefore used a mathematical modelling approach to analyse the proliferative response of TCR transgenic F5 T cells to lymphopenia.

We tested two fundamentally different models of cell division : one in which T cells are triggered into an ‘autopilot’ deterministic burst of divisions (‘Autopilot’ model), a model successfully used elsewhere to describe T cell responses to cognate antigen, and a second contrasting model in which cells undergo independent single stochastic divisions (‘Single divisions’ model). Where as the autopilot model provided a very poor description of the F5 T cell responses to lymphopenia, the model of single stochastic divisions fitted the experimental data remarkably closely. Furthermore, this model proved robust because specific predictions of cellular behaviour made by this model concerning the onset, rate, and nature of division were successfully validated experimentally.

Our results suggest cell division induced by lymphopenia involves a process of single stochastic divisions that is best suited to a homeostatic rather than differentiation role.

Two distinct models of cell cycle control modeled mathematically and tested in the context of homeostatic T cell division

Selected publications

Seddon group

Recent publications

Research projects

Top of page

© MRC National Institute for Medical Research
The Ridgeway, Mill Hill, London NW7 1AA