Special SysGen Seminar – Paul Norman – 10th November, 2016

Human immunity and reproduction drive coevolution of HLA and Natural Killer cell receptors.

Dr Paul Norman
Stanford University, California, US

Thursday 10th November
Agar Theatre, BioSciences 4 (Old Zoology), The University of Melbourne

Combinatorial diversity of KIR and HLA class I molecules directly affects natural killer cell activity. This impacts the outcome of human immune responses to infections and success in reproduction and transplantation. Extensive genetic and functional analyses identified key residues controlling the KIR and HLA interaction, and showed how the molecules coevolve to maximize diversity. In isolated populations of hunter-gatherers from Africa and South America we identified single amino acid residues that alter KIR specificity or function. The variants have dramatic effects on natural killer cell specificity, and likely protect from dangerous pregnancy syndromes. Subject to natural selection, these genetic variants have increased sharply in frequency, and we identified such functionally important alleles in every population so far examined. We also identified similar variants in the genomes of ancient humans and demonstrated their extensive immune legacy in modern humans outside Africa. Finally, we developed methods to sequence HLA and KIR genomic regions in large depth and scale, alongside bioinformatics methods that rise to the challenge of analyzing the highly complex data. The methods, and the substantial database of robust reference sequences we generated will enable future population scale studies of these complicated and clinically important regions of the human genome.

Paul Norman researches the genetics of human immunity. He studies the natural variation in immune responses that evolved as modern human populations expanded and adapted to new environments. His particular focus is co-evolution of the HLA markers for healthy cells and the Natural Killer cell receptors that bind them. To combat infectious pathogens, this system of interacting molecules is so genetically diverse it allows immune individuality. Because this interaction is critical both to immunity and reproduction, natural selection mediates a trade-off to ensure survival of individuals and growth of populations. In this light, Paul has studied African and Amerindian hunter-gatherers, Maoris and Indigenous Australians, and analyzed ancient human’s genomes to trace their immune legacy in present-day populations. Dr. Norman was a fellow of the Lymphoma Research Foundation, and is now a Senior Research Scientist at Stanford University in California.

Enquiries: Andrew Siebel (asiebel@unimelb.edu.au)