David T. Eddington, Ph.D., Associate Professor and Director of Graduate Studies of Bioengineering, has expertise in microfluidic systems. His lab specializes in developing new microfluidic tools to answer biological questions that are not possible with standard lab tools or methods. He has worked in models ranging from yeast to awake and behaving mice and specialized in developing simple solutions that seamlessly integrate into standard biological labs. Some examples include a method to pattern multiple oxygen conditions on brain slices, a microfluidic substrate for perfusion chambers and a method to calibrate cyclic votammetry electrodes. In addition, he has developed other methods which could be adapted to the work including microfluidic devices to assess islet function under intermittent hypoxia, devices that dock to multi-well plates and Boyden chambers, generate oxygen and soluble factor gradients, recreate a sickle cell crisis on a chip, and allow cells to be grown in oxygen sensitive microwells. Other projects in his lab include assessing pancreatic islets prior to transplantation, microfluidic diagnostics for circulating tumor cells, developmental biology and stem cell differentiation, and wound healing. While the end applications are indeed highly variable, all these projects apply similar techniques and methods making his lab a highly multidisciplinary and exciting atmosphere.
Streptococcus pneumoniae is a major global bacterial human pathogen, causing ~1 million deaths annually worldwide, due to pneumonia, sepsis, and meningitis. Two strategies are used to combat such infections. Antibiotics can often cure such infections, and vaccines are used to reduce the circulating populations of the most dangerous serotypes. However, both strategies are failing at an increasing rate. Antibiotic resistant strains are continually arising and spreading globally; vaccination effectiveness is also under challenge, as serotypes not targeted by current vaccine formulations are continually arising and rapidly replace the targeted ones. The cause of these failures is transfer of multiple foreign genes into the bacteria, but the mechanisms creating the new infectious and resistant strain types are unclear. Transfer events are of two types, named as micro- and macro-recombination events. The micro events, involving dozens of hundreds of base pairs, are consistent with the known properties of gene transfer by transformation in pneumococcus. However, the more numerous, and more significant, events involve transfer of multiple blocks of tens of thousands of nucleotides, sometimes all from a single donor strain. These macro-recombination events are difficult to reconcile completely with any known mechanism of gene transfer – whether conjugation, transduction, or transformation. This exploratory project would use microfluidics to create numerous small chambers (droplets) within which attacker-target interactions can be studied and characterized for the first time at both the cellular and molecular levels, by both identifying the participant cells and tracing all gene exchange events at full genome resolution.