353 Award Talk: From omics networks to targets of opportunity in ruminant nutritional physiology.

Abstract The first high-capacity molecular tool, “microarrays”, to monitor the expression of many genes in parallel was developed in 1995, using available information on complementary DNA (cDNA) sequences and expressed sequence tags (EST) from the small flowering plant Arabidopsis thaliana. The microarrays prepared by high-speed robotic printing of these sequences on glass microscope slides in an area measuring 3.5 mm by 5.5 mm were used for expression measurements of 48 genes. Subsequent efforts to sequence entire genomes, including the initial sequencing and analysis of the human genome in 2001, and to develop microarrays for use in functional genomics studies of model organisms (e.g. mouse) and livestock (e.g. chicken and bovine) were instrumental in launching the “omics” era across scientific fields. Bovine-specific microarrays developed at the University of Illinois, Urbana-Champaign, between 2002 (7,872 cDNA) to 2005 (13,000 oligonucleotides) were among the first of their kind used in nutritional and physiological genomics studies of dairy cattle. Application of bioinformatics analyses to transcriptome data generated across the transition into lactation in dairy cow liver, adipose, and mammary tissue, in addition to circulating neutrophils, generated the first glance at gene networks associated with the control of important physiological processes. These included milk fat and protein synthesis, adipogenesis/lipogenesis, and the inflammatory and antioxidant responses. Deployment of these omics tools in studies of postpartal ketosis and inflammatory challenges of the mammary gland also were instrumental in the development of immunometabolism as a core topic in the author’s laboratory. These systematic investigations have facilitated establishing programmatic areas of scientific focus including work with small and exotic ruminants, and in pasture-based dairy production systems, while providing hands-on training for graduate students, post-docs, and visiting scientists from Asia, Central and South America, the Middle East, and Australasia. Several networks identified in this research such as PPAR signaling, ER stress and inflammation, one-carbon metabolism, Calcium signaling, and the antioxidant response via NRF2 signaling have been targeted (in vivo, in vitro) through specific hypotheses involving nutritional interventions. The development of high-throughput sequencing technology replaced microarrays and along with other omics approaches (e.g. metabolomics) and molecular tools (siRNA, CRISPR/Cas9), now constitute important elements in the toolbox supporting global collaborations in ruminant nutritional physiology. Although there is now wider access to cutting-edge technologies in animal sciences, robust training in fundamental aspects of nutrition and physiology will remain instrumental for establishing and validating entirely new paradigms that can provide solutions to the greatest livestock production challenges facing the world.