Elena de Dios Panal

Short description of my project:

Immunological memory, mediated by lymphocytes, allows for quick and effective elimination of pathogens the body has previously been exposed to. In modern medicine we benefit from this mechanism for example by means of vaccination. It has recently become clear that the vast majority of memory T-cells reside in bone-marrow and non-lymphoid tissues, and hence go unnoticed in most immunological studies based on blood or lymphoid tissues. Extremely little is known about the maintenance of these bone-marrow and tissue-resident memory T-cells (T_RM cells). Due to ethical reasons many of these tissues cannot be studied in humans. To complicate it even more, conventional laboratory animals were shown to have an inexperienced immune system with hardly any T_RM cells present. This is why I will study the immune dynamics of T_RM cells in mice with a more experienced, and more natural immune system, closer to the immune system of free living mammals. I aim to use two methods of DNA labelling of proliferating cells: in vivo deuterium labelling and pulse chase labelling with nucleoside analogues (e.g. EdU or IdU). When available in the body, these labels are incorporated into the newly formed DNA of dividing cells. Once the label is no longer available in the body the fraction of labelled DNA decreases when cells die. Based on these changes in label abundance the kinetics of cellular turnover can be quantified using mathematical models (in collaboration with ESR 8, Erdem Şanal).

In the context of human immunity T-cell dynamics in disturbed circumstances are of special interest to me. Therefore in a parallel project, I will use deuterium labelling to study the dynamics of blood derived T-cells in long-term treated HIV patients.