Prof. Ramit Mehr, of the Mina and Everard Goodman Faculty of Life Sciences, is a computational immunologist. Mehr uses mathematical models, computer simulations and bioinformatical analyses to understand the dynamics of lymphocyte repertoires in the immune system in various situations, and predict the results of experimental and medical interventions.
The immune response involves cells of various types, including B, T and NK lymphocytes expressing a large diversity of receptors which recognize foreign antigens and self-molecules. The various cell types interact through a complicated network of communication, regulation and control mechanisms. This is what enables the immune system to perform the functions of danger recognition, decision, action, memory and learning. The dynamics of immune cell repertoires are, as a result, highly complex and non-linear.
B lymphocytes are the cells that create antibodies, and T lymphocytes either kill virally-infected or cancerous cells, or secrete factors that regulate the immune response. Both types of lymphocytes recognize foreign antigens and signs of danger through specific antigen receptors, the genes for which are rearranged from randomly chosen gene segments. Mehr’s lab team has developed mathematical models and computer simulations of the dynamics of the development of T and B lymphocytes, the rearrangement of B cell and T cell antigen receptor genes, and subsequent selection of lymphocyte repertoires, which is based on receptor-ligand interactions. These models are currently being applied to the understanding of immune system aging.
Natural killer cells are also lymphocytes that kill virally-infected or cancer cells, but they do this through recognition of markers of cell stress. Mehr’s group is working on models for the development of natural killer (NK) cells and their repertoire, from receptor gene expression to selection of functional, non-harmful cells, and the dynamics of NK cell activation.
In addition, Mehr’s group is studying the competition between B lymphocyte clones during the humoral immune response, the process of hypermutation and the creation of memory cells, including the explanation of the phenomenon of repertoire shift, isotype switch, and graph-theoretical analysis of B lymphocyte immunoglobulin gene lineage trees.
Mehr and her team have developed a new method for analyzing the mutations in antibody genes, which occur during an immune response. This method is based on lineage tree analysis, and enables them to follow the dynamics of antibody-forming cells in response to vaccines, autoimmune responses, or lymphomas. Their work has demonstrated that the processes triggering cell death or promoting survival in lymphoma cells – as well as those cells involved in the chronic inflammation that can lead to cancer – are different from the factors that determine cell death and survival in normal, non-cancer-related cells.