How does biological individuality come about? This is a fundamental question in biology. At qob we study the vertebrate immune system as a case study to address questions on biological individuation in quantitative and testable ways. Lymphocytes and other cells of the immune system contribute to body housekeeping and homeostasis, pathogen elimination, commensal microorganism assimilation, and, normally, avoid immunopathologies, such as autoimmune diseases and allergy. They do this collectively in ways that are unique in each individual. This uniqueness reflects a striking process of individuation, that is captured in the concept of 'immunological self', and in the convictions that the immune system 'distinguishes self from nonself', senses 'danger' and detects menaces to 'self-integrity'. At qob we study the development natural tolerance that leads to 'immunological self' and the breakdown of this process during in autoimmune diseases. In particular, we study the population dynamics and repertoire selection of regulatory CD4+Foxp3+ T cells that are key players in these processes. We put forward the Crossregulation Model that provides a comprehensive view of regulatory T cell immunobiology. This model inspired the creation of spam detection algorithms, and is being redeployed as novel control strategies in collective robotics.
Cells and whole organisms display a significant phenotypic variation that can not be ascribed to variation in the genome. In multicellular organisms this variation creates the potential for somatic adaptation by selective expansion of phenotypic variants in detriment of others. The hallmark of such somatic variation and adaptation is the vertebrate immune system, where the gene encoding the antigen receptor of lymphocytes do not exist as such in the germline genome, but are generated by recombination and mutation of precursor gene segments. These antigen receptors control the life history of lymphocytes and the interactions they make among them and with other cells, leading to adaptation by clonal expansion of variant lymphocyte lineages. The actual repertoire of antigen receptor variants is what confers the uniqueness to each individual. But there are even more pervasive forms of somatic variation: The numbers per cell of molecules that control cell physiology, cycle, and apoptosis display long-tailed distributions in cell populations of isogenic cells. These distributions in key molecular components were observed in prokaryotic or eukaryotic free-living cells as well as in cells of multicellular organisms. At qob we are interested in the sources of this variation and in its implications for the physiology of the cell and of the organism.
Understanding how tissue and body shape comes about involves, as an absolute prerequisite, understanding the shape changes of individual cells. At qob we investigate several case studies of individual cell morphodynamics in three dimensions, namely pollen tube apical growth and navigation, sea urchin sperm swimming and chemotaxis, and mammalian cell motion, adhesion, and cell-to-cell interactions. These case studies are building blocks of a quantitative framework to deal with the tissue morphodynamic processes involved in differentiation patterns and morphogenetic movements during embryo development.
Symmetry breaking by Turing-Meinhardt instability and Wolpert's positional information are two key principles for thinking about cell polarization, tissue patterning, and embryo development. Some animal body symmetries, however, cannot be easily understood under these principles. Left-right asymmetry in internal organs of vertebrates is one such patterns that demand a quantitative explanation. Current views are based on symmetry breaking due to chiral structures, such as cilia. At qob we investigate the development of body left-right axis.
