The objective of the Genomics, Epigenomics and Proteomics Core (GEP; Core C) is to provide genomics, epigenomics and proteomics/metabolomies support to each of the three projects for the following tissues: placenta (Project I), fetal frontal cortex (Project II) and fetal kidney (Project III). Genomics, epigenomics and targeted epigenetic experiments will be performed in Dr. Cox's laboratory at TBRI. Proteomics and metabolomics analyses will be conducted in Dr. Weintraub's laboratory at UTHSCSA. The technologies necessary to support all three projects are in current use in the Pis' laboratories. Epigenomic, proteomic and metabolomic, network and multidimensional network studies will be conducted using state-of-the-art technologies and software tools. Targeted genomic and epigenomic analyses will be directed by discoveries from network analyses of epigenomic and proteomic datasets and take advantage of established methods in our research groups to begin to understand nutrient-responsive epigenetic mechanisms. This approach will provide information for each Project on transcriptional, post transeriptional and translational regulation in response to maternal nutrient restriction (IVINR) and MNR intervention (INT) compared to control diet (CTR). Core C services will generate data from placenta, fetal frontal cortex and fetal kidney for CTR, MNR and INT diets at 140 and 180 days gestation including: 1) small RNA transcriptome sequence and abundance; 2) RNA transcriptome sequence, splice variants, transcription start site (TSS) variants; 3) protein identification/abundance; 4) metabolite analysis; 5) identification of nutrient responsive, coordinated molecular networks; and 6) insight into nutrient responsive epigenetic mechanisms underlying the IUGR phenotype. In addition, the GEP core will organize the large datasets into a database accessible by investigators in the Projects. Bioinformatic approaches including Pathway Analysis will be used to integrate the multiple datasets from the three tissues into high-dimensional networks as a central step in developing a systems analysis of both normal and restricted growth in the developing nonhuman primate fetus.
Reduced fetal nutrient availability results in suboptimal fetal growth and development that increases the risk of lifelong ill health including the predisposition to diabetes and cardiovascular disease. This Program integrates decreased maternal nutrient availability with placental function, fetal nutrient availability and fetal brain and kidney development. Core C will conduct the genomics, epigenomics and proteomics analyses that support the goals of each Project.
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