I use theoretical and computational approaches to study immunology, the within-host dynamics of pathogens, and to connect the epidemiology of disease (between-host dynamics) with immunological (within-host) processes. I like to collaborate with experimental biologists wherever possible. A few examples of the topics that interest me currently are:

The population biology of immune repertoires: generation, structure, quality and persistence
How flexible is our capacity for immunological memory? What determines the longevity of our protective memory to a particular infectious agent or vaccine? How does our naive T cell repertoire develop throughout childhood? How are our immune repertoires reconstituted in lymphopenic conditions? How do lymphocytes integrate signals from their environment, and what determines the size of any particular T or B cell clone? What happens to the clonal structure and functional integrity of our naive and memory lymphocyte populations as we age?

The dynamics of CTL killing
There is currently much interest in developing vaccines that elicit strong cytotoxic T lymphocyte (CTL) responses as well as humoral immunity. However, in contrast to the soluble, rapidly diffusing antibodies constitutively produced by memory B cells, CTL need to undergo reactivation, migrate to an infection site, rapidly survey potential targets and identify and kill infected cells efficiently. Understanding the spatio-temporal dynamics of CTL activity is essential for understanding T cell vaccine efficacy. I am also using structured population models to look at the effect of CTL control on viruses with different reproductive strategies.

The within-host dynamics of infections
What are the relative contributions of immunity and resource limitation in controlling acute infections? Why and how do many infections persist? What programs do immune cells follow in response to these infections and how are these self-limited or subverted? Much of what governs the life-histories of cells participating in an immune response is poorly defined, particularly in the later stages of infections. TB, Malaria, HIV, tumours and grafts are diverse examples or analogues of chronic infections, and a deeper understanding of the dynamics of persistently stimulated immune cell populations is crucial for understanding and treating the associated pathology. Addressing such questions requires linking the dynamics of processes within cells (for example, differentiation and senescence) with the population biology (ecological dynamics) of lymphocytes.