Functional and comparative immunology of a teleost's world without MHC II
About the project
The mechanisms underlying the vertebrate immune response are remarkably complex. The fact that core elements of this system have been conserved since its emergence in the jawed vertebrate ancestor underscores the importance of the immune system as a crucial component for host persistence. Remarkably, we have previously shown that Atlantic cod (Gadus morhua) has lost the major histocompatibility complex (MHC) II system. In humans, defects in this system lead to immunodeficiency and death. Moreover, specific gene expansions suggest that the Atlantic cod immune system has evolved alternative strategies to cope with this loss. Nevertheless, an evolutionary, functional and co-evolutionary understanding of this unique phenomenon is lacking. Here we will investigate these issues through a multidisciplinary approach, by exploiting recent advances in genomics and state-of-the-art immunological functional tools. First, we will sequence a range of teleost lineages to investigate the evolutionary origin of the Atlantic cod immune system with an aim to associate biological or environmental factors to the loss of MHC II and to investigate the necessity for alternative immunological strategies to emerge. Second, through in vitro and in vivo immunological experiments, we will provide a deeper understanding of the basic function of this immune system, potentially uncovering novel immune functionality at the gene or pathway level. Finally we aim investigate whether the loss of MHC II has an effect on the composition of the microbial community in teleosts, which would emphasize the important role of host-pathogen co evolutionary dynamics. Overall, this work will generate a deeper understanding about the diversity and evolution of the vertebrate immune system, widening a perspective that has so far been restricted by the preferential use of mammalian model systems.
Oslo University Hospital
This project is funded by The Research Council of Norway.
01.04.2013 - 30.06.2016