Evolutionary genetic dissection of the genus Homo and its immune response
Lluis Quintana-Murci is Director of Research at the CNRS and Professor at the Institut Pasteur. He heads the Unit of Human Evolutionary Genetics (CNRS UMR2000) at the Institut Pasteur (Paris) since 2007, and has been Scientific Director of the Institut Pasteur in 2016-2017. He earned his Ph.D. in Population Genetics at the University of Pavia (Italy), and his MSc in Biology at the University of Barcelona (Spain). He is a population geneticist whose research focuses on the study of the genetic architecture of human populations and the role of genetic diversity in human adaptation. In particular, his laboratory uses genomic data to infer the past demographic history of human populations, with a focus on Africa, and dissect the different forms in which natural selection can act on the human genome. His team is especially interested in exploring the extent to which pathogens have exerted pressures on human innate immunity genes. Over the last years, his team has also adopted a systems immunology approach to understand the different factors (genetic, epigenetic, environmental, etc.) that drive immune response variation between individuals and populations. To this end, they correlate genetic and epigenetic variation in populations with different ancestries and lifestyles with molecular phenotypes (mRNA/miRNAs expression, proteins and metabolites) related to immune responses, to identify mechanisms that have been crucial for our past and present survival against infection. These studies should help to lay the foundations of precision medicine related to infectious and immune-related disorders and vaccine treatment. His laboratory combines molecular and population genetics approaches, with computational modelling and development of new statistical frameworks. Lluis Quintana-Murci has co-authored over 200 publications on fundamental population genetics as well as evolutionary genetics of infection and published 7 book chapters. He has received several awards, including the CNRS Bronze Medal (2008), the Dagnan-Bouveret Award from the French Academy of Sciences (2009), the Debiopharm- EPFL Life Sciences Award (2009), the CNRS Silver Medal (2013) and the Grand Prix of Medicine and Medical Research of the City of Paris (2014). He was a laureate of the European Research Council (ERC), and is a member of EMBO and the Academia Europaea since 2014. From October 2019, Lluis Quintana-Murci has been appointed Professor at the Collège de France, with the chair Human Genomics and Evolution.
Thursday 28 November 2019 (12h15 - 13h00) - Génopode - Auditoire A
Unravelling the contributions of host and environmental factors to inter-individual and inter-population variability in immune responses is crucial to understand immune pathology. There is growing biomedical interest in studies of the variation of the immune response and its determinants in the healthy population ¾ in a strategy known as systems or population immunology. Here, I will present our recent studies aiming to dissect the genetic, non-genetic and evolutionary determinants of immune response variation. The role played by pathogens in shaping human immune diversity is clearly attested by population genetic studies, indicating that immunity and host defense functions are among those most frequently subject to natural selection, whether purifying, positive or balancing. Notably, we have shown that population adaptation to novel pathogen pressures can be facilitated by the acquisition, via admixture, of advantageous alleles from local “adapted” populations, such as Neanderthals or modern humans. I will also discuss our work on how genetic variation, whether adaptive or not, affects the diversity of molecular phenotypes (i.e., gene expression-eQTL, alternative splicing-sQTL, and DNA methylation-meQTL), and highlight the importance of inferring the causality behind the detected associations between genetic, epigenetic and transcriptional variation. Finally, I will present our recent data on the respective contributions of genetic and non-genetic factors, such as age and sex, to the diversity of both transcriptional responses to microbial challenges and epigenetic marks. This presentation will attempt to provide a glimpse into how population and functional genomic approaches can help to pinpoint evolutionarily important determinants of host immune responsiveness and, more generally, shed new light onto the foundations of precision medicine approaches.