Humans and our close evolutionary relatives respond differently to a large number of infections. While AIDS, malaria, and cancer kill millions of humans around the world every year, several non-human primates appear to be naturally protected against these diseases. Such differences between humans and other primates are thought to be the result, at least in part, of inter-species differences in immune response to infection. However, due to the lack of comparative functional data across species, the ways in which the immune systems of humans and other primates differ remain unclear. In the laboratory, we are studying the phenotypic evolution of immune responses in primates by combining in-vitro immunological assays with cutting-edge genomic techniques. Our projects promise to identify inter-species differences in early response to infection that may explain differences in susceptibility to diseases among primates
In collaboration with George Perry (PJ) and Nathaniel Dominy we established a field site in Uganda where we have been working with a population of Eastern Pygmies, the Batwa. The long-term goal of this project is to build a comprehensive picture of the demographic and evolutionary events that contributed to the evolutionary history of this population of rainforest hunter-gatherers. Our lab is particularly interested in understanding how the advent of agriculture impact on our relation with pathogens. Indeed, it has been proposed that the advent of agriculture at the beginning of the Neolithic period, 10,000 years ago, resulted in an increased burden of infectious diseases. We are formally testing this hypothesis by performing comparative studies of immune response between the Batwa (hunter-gathers) and their neighboring agriculturalist population, the Bakiga, and study whether the observed differences have been the result of differential selective pressures.
Tuberculosis is a major public health problem. One-third of the world’s population is estimated to be latently infected with Mycobacterium tuberculosis (MTB), the etiological agent causing tuberculosis (TB), and active disease kills nearly 2 million individuals world-wide every year. A striking feature of TB is that only 10% of infected individuals develop the disease. Although genetic studies of TB have identified important pathways involved in protective immunity, very little is yet known about the underlying genetic determinants or mechanisms contributing to differences in susceptibility to TB at the population. Our lab in collaboration with Ludovic Tailleux, Yoav Gilad and John Marioni is using a combination of empirical and statistical approaches to identify genes and regulatory pathways that contribute to inter-individual variability in the immune response to infection with Mycobacterium tuberculosis. Specifically, we are studying inter-individual variation in the immune transcriptional response of phagocytic cells (dendritic cells and macrophages) following infection with MTB, and map the genetic loci that are associated with such variation (eQTLs). In addition, we are also interested in understanding to which extent epigenetic changes (primarily methylation) play an important role in immune responses to MTB.
Infectious diseases have always been a major public health problem throughout the world. Despite the recent development of vaccines and antibiotics, there are still nearly 15 million deaths every year attributable to the effects of infectious diseases. Although a significant proportion of inter-individual variation in susceptibility to particular microbes can be attributed to environmental factors such as malnutrition or poor hygienic conditions, a substantial portion is due to host genetic factors. Yet, to date, very little is known about the underlying genetic factors that contribute to differences in susceptibility to infectious diseases at the population level. Using a multidisciplinary approach that combines cutting edge genomic techniques with immunological and evolutionary genetic tools, our lab aims to identify individual genes, as well as entire pathways, whose transcriptional response to distinct bacterial infections varies among individuals and populations and can be mapped to specific genetic loci (QTLs). Successful mapping of such QTLs will result in the identification of highly-promising genetic candidates of susceptibility to infectious diseases.