Research in the BIOTRANS program can be loosely considered as falling into three different areas corresonding to different size scales. One objective of our program is to pursue research problems and solutions that span these three areas.
transport at the cellular scale
Cellular-scale biological functions such as division, signaling, and motility depend on transport within and across membrane-bound compartments. Most biochemical models assume that these cellular processes take place in dilute solutions, but the cellular environment is far from a diffuse fluid environment. Molecular crowding can profoundly affect in vivo reaction kinetics and delivery of chemical- and nanoparticle-based therapeutic agents (connecting with the organismal scale) to the proper subcellular location. By integrating practical biochemical and biological laboratory experience with engineering models of complex transport, BIOTRANS researchers are able to predict, model, and experimentally test how thermodynamic, electrodynamic, and mass transport phenomena give rise to higher order information transfer within and between complex metabolic systems. Such an interdisciplinary reductionist approach by BIOTRANS researchers is critical to achieving the level of understanding that is currently missing in efforts to engineer cells for applications ranging from human health to the development of alternative energy sources and chemical feedstocks. The BIOTRANS team is also involved in developing microfluidic technologies that build understanding of cellular responses to stimuli at the molecular level, within and between cells, and with surrounding materials and the environment. We are able to capitalize on the infrastructure in place at Virginia Tech for studying cellular-based micro-systems, including advanced imaging and characterization facilities.
transport at the organismal scale
BIOTRANS researchers are studying organismal-scale transport mechanisms ranging from the exchange mechanisms of individual organs and the cardiovascular and respiratory systems, to transport through endothelial layers and within interstitial tissue, and down to the cellular and subcellular level (connecting with cellular-scale transport). Organismal transport of engineered particles is of particular interest. It has been shown that nanoparticles are released into the atmosphere during certain manufacturing processes (connecting with environmental scale transport), and it is expected that nanomaterials will find their way from consumer products into surface waters. Humans and other animals can then be exposed to nanoparticles either in drinking water, food contaminants, or inhaled air. Researchers have shown that the uptake of certain nanoparticles can be hazardous, with organisms often unable to remove the particles from the system. On the other hand, recent advances in drug delivery methods have successfully optimized the characteristics of drug carrying vesicles. However, the success of these new methods hinges on efficient transport of particles to the diseased site. Important questions about the transport of engineered particles within an organism, either incidental or by design, remain unanswered, and the mechanisms of such transport have not yet been fully elucidated. In addition, heat-transport-based treatments are now emerging as attractive alternatives to conventional particle or drug delivery. Locally induced hyperthermia in the region of tumors or plaques offers targeted therapies that are free of toxic side effects. Magnetic nanoparticles forced to rotate using a cycling magnetic field can create a highly localized hyperthermia that does not harm surrounding healthy organs and has yielded promising results. BIOTRANS trainees will be provided with the tools and experience necessary to make advances in these important multi-scale, multi-physics problems.
transport at the environmental scale
The spread of disease, pollution, incidentally released pharmaceuticals, and engineered particles by water and air depends on a wide range of scales and systems, from local infection of the host and details of physiological transport (connecting with organismal transport) to long-range environmental transport. For example, the US Environmental Protection Agency (US EPA) reports that over 9000 bodies of water in the United States are not suitable for swimming and other uses because of high bacteria levels. Bacteria are typically transported by eroded sediment; thus accurate sediment monitoring and modeling is key to understanding bacteria fate and transport in aquatic ecosystems. To understand and control the effects of environmental transport, BIOTRANS trainees must first understand the underlying physical and biological mechanisms. Although features of the Earth’s surface and near-surface complicate the details of this transport, the long-distance movements and effects of small particles are indeed predictable. Making accurate transport forecasts requires BIOTRANS researchers to couple dynamical systems tools for modeling transport dynamics with the mechanical and biological response of organisms to their environment.