Most in vitro devices for studying how humans respond to chemicals use  isolated cells of a single type and do not permit exchange of metabolites  between tissues. Professor Michael Shuler, chair of the Department of  Biomedical Engineering, is improving upon these static models by creating  a dynamic system for toxicological and pharmaceutical testing.

Shuler has fabricated a micro-scale cell culture analog, sometimes  referred to as an “animal on a chip,” that uses live, mammalian cells  cultured in interconnected chambers to represent a physiologically based  pharmacokinetic model—a mathematical simulation of mammalian  responses to chemicals and drugs through uptake, distribution,  metabolism, and elimination. The device’s four organ-mimicking chambers  could be called its lungs, liver, fat, and “other tissue.” A micro-pump recirculates  a culture medium that acts as a blood surrogate and allows for  an exchange of metabolites.

Long-term, the goal of Shuler’s research team is to enable the  manufacture of realistic, inexpensive devices. At present, the device is built  on a one-inch-square silicon chip.

“For real applications, simple cell lines are a poor imitation of actual  organs. But we’ll keep refining our system until it can accommodate more  accurate tissue-engineered specimens,” Shuler says. “Then, we should be  able to produce real insight into the molecular mechanisms of toxicity.”

Professors Dave Putnam, Biomedical Engineering, and Matt DeLisa, Chemical and Biomolecular Engineering, are collaborating to develop better ways to deliver pharmaceuticals (drugs, proteins, or genes) using viral and non-viral gene vectors.

Delivering DNA to cells is difficult, but viruses have evolved to perform the task elegantly; so Putnam and DeLisa are attempting to mimic a virus in order to deliver a vaccine. One of Putnam’s core research areas focuses on developing an artificial virus using polymers.

This research team is also looking at a new way to deliver DNA to the body by engineering bacterial products to mimic viruses. By taking sloughed off outer-membrane vesicles of bacteria and engineering their surfaces to entice the immune system to recognize it, and then packing the vesicles with DNA, they hope to trick the body into mounting an immune response to the DNA, leading to efficient vaccination of the patient. At this stage, they use only marker DNA. Putnam, who has a joint appointment in the School of Chemical and Biomolecular Engineering, works on delivery and stability; DeLisa does the bacterial work.

DeLisa focuses on the performance of complex protein machines, exploring ways to engineer bacteria with new or improved protein processing machinery to help solve problems that cannot be solved using natural systems. His approach is to supercharge bacterial protein production by going inside the cell itself. For example, he’s replacing key parts of the bacteria’s protein-making machinery with components from higher organisms to produce finely tuned miniature drug factories.