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.

Plant Migrations Impact on Potential Vegetation and Carbon Redistribution in Northern North America from Climate Change

Forests have a prominent role in carbon storage and sequestration. Anthropogenic forcing has the potential to accelerate climate change and alter the distribution of forests. How forests redistribute spatially and temporally in response to climate change can alter their carbon sequestration potential. The driving question for this research was: How does plant migration from climate change impact vegetation distribution and carbon sequestration potential over continental scales? Large-scale simulation of the equilibrium response of vegetation and carbon from future climate change has shown relatively modest net gains in sequestration potential, but studies of the transient response has been limited to the sub-continent or landscape scale. The transient response depends on fine scale processes such as competition, disturbance, landscape characteristics, dispersal, and other factors, which makes it computational prohibitive at large domain sizes. To address this, this research used an advanced mechanistic model (Ecosystem Demography Model, ED) that is individually based, but pseudo-spatial, that reduces computational intensity while maintaining the fine scale processes that drive the transient response. First, the model was validated against remote sensing data for current plant functional type distribution in northern North America with a current climatology, and then a future climatology was used to predict the potential equilibrium redistribution of vegetation and carbon from future climate change. Next, to enable transient calculations, a method was developed to simulate the spatially explicit process of dispersal in pseudo-spatial modeling frameworks. Finally, the new dispersal sub-model was implemented in the mechanistic ecosystem model, and a model experimental design was designed and completed to estimate the transient response of vegetation and carbon to climate change. The potential equilibrium forest response to future climate change was found to be large, with large gross changes in distribution of plant functional types and comparatively smaller changes in net carbon sequestration potential for the region. However, the transient response was found to be on the order of centuries, and to depend strongly on disturbance rates and dispersal distances. Future work should explore the impact of species-specific disturbance and dispersal rates, landscape fragmentation, and other processes that influence migration rates and have been simulated at the sub-continent scale, but now at continental scales, and explore a range of alternative future climate scenarios as they continue to be developed.