Minisymposium/CEES Extra seminar: Lectures by Mary J. O'Connell and Tobias Lenz
Lecture titles: "On the malleability of proteins and the emergence of novel function" and "Evolutionary trade-offs in the adaptive immune system shape genomic diversity of the MHC"
On the malleability of proteins and the emergence of novel function
Dr Mary J. O'Connell, Associate Professor, The O'Connell Lab, Computational & Molecular Evolutionary Biology Group, The University of Nottingham, U.K.
Abstract: In my research group we combine computational biology and genome scale analyses with molecular/biochemical assays. I am interested in the tipping point that can occur between purifying selection which preserves function and positive selection that switches function. In essence, I am interested in understanding when protein function changes, where it changes, and how it changes. In this talk I will summarise work we have carried out to explore the emergence of novel function and the relationship between genotype and phenotype.
Evolutionary trade-offs in the adaptive immune system shape genomic diversity of the MHC
Dr. Tobias Lenz, Group Leader, Max Planck Institute for Evolutionary Biology, Germany
Abstract: An optimal immune response requires a delicate balance of maximizing pathogen recognition while minimizing damage to own tissue by the activated immune machinery. In vertebrates, this process is mediated by the highly polymorphic major histocompatibility complex (MHC), whose molecules present both self and foreign peptides for recognition by immune effector cells. This leads to a quantitative trade-off: Presenting many peptides is good for pathogen resistance but also increases the risk of autoimmunity. Here I present the underlying conceptual framework as well as empirical data elucidating both sides of this trade-off. Population-level computational analysis as well as data from HIV patients support pathogen-mediated selection for increased individual MHC diversity. On the other hand I will show evidence for a positive association between individual MHC diversity and risk for autoimmunity as well as experimental results elucidating MHC-dependent T cell repertoire depletion. Such antagonistic forces select for an intermediate level of individual MHC diversity, as observed in natural populations. Studying these trade-offs sheds light on the evolutionary and genetic basis of inter-individual differences in immunocompetence within and among populations.