Therapeutic Potential of RNAi Through Endocytotic Methods

The ability to manipulate gene expression promises to be an important tool for the management of infectious diseases and genetic disorders. However, a major limitation to effective delivery of therapeutic RNA to living cells is the cellular toxicity of conventional techniques. Team PANACEA’s research objective was to create new reagents based on a novel small-molecule delivery system that uses a modular recombinant protein vehicle consisting of a specific ligand coupled to a Hepatitis B Virus-derived RNA binding domain (HBV-RBD). Two such recombinant delivery proteins were developed: one composed of Interleukin-8, the other consisting of the Machupo Virus GP1 protein. The ability of these proteins to deliver RNA to cells were then tested. The non-toxic nature of this technology has the potential to overcome limitations of current methods and could provide a platform for the expansion of personalized medicine.

Integrative genomic, epigenetic and metabolomic characterization of beef from grass-fed Angus steers

Beef constitutes a main component of the American diet and still represent the principal source of protein in many parts of the world. Currently, the meat market is experiencing an important transformation; consumers are increasingly switching from consuming traditional beef to grass-fed beef. People recognized products obtained from grass-fed animals as more natural and healthy. However, the true variations between these two production systems regarding various aspects remain unclear. This dissertation provides information from closely genetically related animals, in order to decrease confounding factors, to explain several confused divergences between grain-fed and grass-fed beef. First, we examined the growth curve, important economic traits and quality carcass characteristics over four consecutive years in grain-fed and grass-fed animals, generating valuable information for management decisions and economic evaluation for grass-fed cattle operations. Second, we performed the first integrated transcriptomic and metabolomic analysis in grass-fed beef, detecting alterations in glucose metabolism, divergences in free fatty acids and carnitine conjugated lipid levels, and altered β-oxidation. Results suggest that grass finished beef could possibly benefit consumer health from having lower total fat content and better lipid profile than grain-fed beef. Regarding animal welfare, grass-fed animals may experience less stress than grain-fed individuals as well. Finally, we contrasted the genome-wide DNA methylation of grass-fed beef against grain-fed beef using the methyl-CpG binding domain sequencing (MBD-Seq) method, identifying 60 differentially methylated regions (DMRs). Most of DMRs were located inside or upstream of genes and displayed increased levels of methylation in grass-fed individuals, implying a global DNA methylation increment in this group. Interestingly, chromosome 14, which has been associated with large effects on ADG, marbling, back fat, ribeye area and hot carcass weight in beef cattle, allocated the largest number of DMRs (12/60). The pathway analysis identified skeletal and muscular system as the preeminent physiological system and function, and recognized carbohydrates metabolism, lipid metabolism and tissue morphology among the highest ranked networks. Therefore, although we recognize some limitations and assume that additional examination is still required, this project provides the first integrative genomic, epigenetic and metabolomics characterization of beef produced under grass-fed regimen.