The major histocompatibility complex in humans, HLA, is the focus of my investigations. It is both the most polymorphic locus of our genome and the most directly involved in the adaptive immune response and the rejection of tissular transplants. Therefore, it is not only interesting for research in human evolution, but also for the understanding of genetic susceptibility or resistance to diseases and for the search of compatible bone marrow or organ donors for patients needing a transplant. Our research is thus also motivated by public health issues.
Since 1996, my group, with Dr José Nunes, plays an important role in the international coordination of research on the molecular diversity of the HLA system within the framework of successive International HLA and Immunogenetics Workshops (IHIW). Since 2009, we also lead HLA-NET (http://hla-net.eu), a large European network aiming at implementing population data, standards of analysis, aswell as statistical and computer tools for the study of HLA diversity at the population level. Such developments are essential both for analyzing human genetic evolution and for searching compatible donors in transplantation. In this context, we closely collaborate with the National Reference Laboratory for Histocompatibility (LNHR) located in the HUG (Dr J-M Tiercy and J.Villard) and the Swiss Blood Stem Cells Foundation which manages the national registries of stem cells donors in Bern.
Within the framework of our investigations on human peopling history, we adopt an interdisciplinary approach according to which our genetic results are faced to paleontology (study of fossils), prehistoric archaeology (study of cultural vestiges), historical linguistics (study of the evolution of language families),and epidemiology (study of pathogens, diseases and their evolution). In this context, we collaborate with different teams of anthropologists, archaeologists, linguists and geneticists. Our projects, regularly funded by the National Swiss Foundation for Scientific Research (FNS) for more than 20 years, addresses questions related to the genetic history of diverse continents of which sub-Saharan Africa, the likely homeland of modern humans, but also East Asia and Europe.
At the level of the genome, our works lead us to propose essential hypotheses on the molecular mechanisms governing the evolution of the HLA system (asymmetric balancing selection or purifying selection, depending on the loci). This mode of evolution is compared with that of other human polymorphisms, such as classical markers and, in collaboration with Dr E. Poloni, mitochondrial DNA and Y-chromosome polymorphisms. The experimental approaches by computer simulation developed by Dr Mr Currat also serve us, for some years, to test the likelihood of the scenarios of peopling history proposed in our projects and to estimate quantitatively the effects of natural selection on the evolution of the HLA system.