Functional Genomics of the Immune System

When a pathogen manages to surpass our skin, or any of the mucous membranes of our bodies, our immunological defences activate. As a reaction to the infection, the immune system deploys a complex response with the only objective of keeping us safe from the invader, either by killing it, or, at least, by containing it until it represents no threat.

The outcome of such a complex process is seldom a consequence of a single cause. Instead, according to a more accurate lecture of the phenomenon, the adequacy of the immune response to an infection challenge is viewed as a consequence of a complex interplay between many different causal factors. These factors equally stem from the genetics of both host and pathogen as well as from the environmental context wherein they meet.

In the context of my work in Dr. Barreiro’s lab in Montreal, I study such causality links from genotypes and environments to immune response to infection. Our main objective in the lab is the identification of the most relevant aspects, both environmental and genetic, that shape immune function in humans and primates. Equally important, we aim to identify the components of that response (functions, pathways and genes) that are more affected by such causal factors, and the evolutionary and clinical implications of those.

immunogenomics

Experimental approach to the study of the functional genomics of the Immune System. In Dr. Barreiro’s lab, we are interested in identifying genetical and environmental factors impacting the ability to respond to immune challenges in humans and primates.

To do that, our experimental framework is based on a series of robust in-vitro models of infection. Using this approach, we infect different types of immune cells with live pathogens; and register a series of molecular phenotypes that provide useful information about the stiffness of the response of the host cells to the immune challenge. That includes measures of genome wide host gene expression and epigenetic profiling (RNAseq, AtacSEQ), pathogenic clearance rates and cytokine secretion levels, among others. By performing these assays on large panels of samples from individuals that differentiate in relevant aspects, either genetic and/or environmental, we are able to identify how such aspects influence immune response in the controlled context of our in-vitro assays.

In what regards the influence of host’s genetics in immune response, my recent interests include the characterization of inter-population differences between African- and European- descendants in response to bacterial pathogens, as well as the study of the evolutionary consequences in human immune function that derive from the adaptation to Agricultural life styles at the onset of the Neolithic period.

Complementarily, we are interested in the study of the effects that social stress, adversity and status exert on the immune system. To tackle this fundamental problem, one classical limitation comes from the fact that social stress in humans come with a series of confounding risk factors (i.e. worse life conditions, differences in nutrition, deleterious habits etc.) that makes difficult to identify its true, direct effects on health. To solve this problem, we study social subordination in controlled, hierarchical populations of rhesus macaques, and how it affects immune response to an immune challenge.

 

 

 

 

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