Ahmad Khalil: Building Devices, Building Cells
Assistant professor, Boston University
Recommended by James Collins, Boston University
Ahmad Khalil started out studying how to build things like rocket engines and other mechanical systems as a mechanical engineering major in college. But, he added, he also took a liking to biology and the idea of applying engineering ideas to the study of living systems.
His PhD mentor, Angela Belcher at MIT, impressed upon him the reverse as well, that biological systems could also be used to engineer materials, and from her, he said, is where he got his "inspiration for bio-inspired engineering."
In his new lab at Boston University, Khalil is studying how cells respond to various environmental conditions and stressors.
"We develop engineering approaches and technologies to broadly study how cells behave, how they grow, how they develop, how they communicate," Khalil said, "and, in turn, to also re-direct those behaviors for useful applications for human health and energy and societal problems."
Additionally, Khalil and his team are building microfluidic devices to study cell behavior. For instance, he said that they can grow cells within these devices and watch in real time as they respond to different conditions like various growth media, stressors, or antibiotics.
His group is also using synthetic biology to build networks. He and his group are designing new transcription factors and networks so that they can, in the long run, engineer cells and turn genes on or off.
Khalil's group is just getting off the ground and he said that one of the challenges as a new principal investigator is juggling the various projects the lab is tackling. As a graduate student or postdoc, he noted, he was generally focused on one or two projects while now he is overseeing between five and 10 projects as well as a number of collaborations.
"Having the delicate balance of relieving yourself from all the technical nitty-gritty, but having just the right level of engagement has been absolutely the most challenging thing for me," he said.
Paper of note
Much of the work in Khalil's lab draws upon two papers that he published as a postdoc in James Collins' lab at BU.
In one, appearing in Nature Chemical Biology in 2012, Khalil and his colleagues described how they designed a microfluidic system to study microbial drug persistence — bugs that are not resistant to the drugs but that manage to survive anyway.
They put individual bacterial cells in the device and added antibiotics to watch the formation of such persisters. From this, they uncovered that bacteria can signal to one another that there is a stress and inoculate themselves by activating a stress response.
In the other, which was published in Cell that same year, Khalil and his colleagues reported on a way to use artificial zinc finger proteins as site-specific transcription factors. They then developed a library of those transcription factors and, in yeast, used them to make synthetic transcriptional circuits.
"It uses this really interesting bottom-up approach to try to understand things like transcription regulation and it provides a new tool kit for synthetic biology," Khalil said.
Synthetic biology as a field has a few challenges to tackle in the near future, Khalil noted. It's a young field that has made a few promises. In the coming years, Khalil said, it needs to make good on some of that promise, even if it is in a modest application to show that synthetic biology can be used to tackle problems in health, energy, or the environment. Then, he added, it will become a more accepted way to study living systems.