Pitt engineer’s research on magnetically activated engineered cells attracts NIH funding
During graduate school at Carnegie Mellon University (CMU) in Pittsburgh, Warren Ruder wondered if it might be possible to genetically engineer cells to respond to magnetic fields. When implanted in the body, cell-based therapies could then be fine-tuned by exposing a patient to a magnetic field. Though the necessary technology to pursue this project did not exist at the time, Ruder has found himself back in Pittsburgh a decade later with diverse training, advanced technology, and a significant NIH award to now further his original idea at the University of Pittsburgh's Swanson School of Engineering.
Ruder, now an assistant professor at the Swanson School's Department of Bioengineering, was one of 58 researchers to be awarded $1.5 million with the competitive and prestigious NIH Director's New Innovator Award. Established in 2007 under the High-Risk, High-Reward Research program, this award supports "exceptionally creative scientists proposing high-risk, high-impact research," according to the NIH.
Ruder's research group works at the interface of biology and engineering to create new biomimetic systems that provide insight into biological phenomena while also serving as platform technologies for future medical applications. He plans to combine his backgrounds in synthetic biology and biomimetics for this project titled "Creating Magnetically Inducible Synthetic Gene Networks for Cell and Tissue Therapies."
Ruder's background in biomechanics and biomimetics started as an inaugural trainee in the Joint Pitt-CMU Biomechanics in Regenerative Medicine Training Program in 2005, where he learned to manipulate the cell environment, particularly with magnetics.
"During my graduate studies in Pittsburgh, I learned how to use magnetic tensile cytometry – a form of magnetic tweezers – to place very small forces on the membrane of mammalian cells," said Ruder. "I was also introduced to biomimetics and learned to create microscale and nanoscale systems – such as lab-on-a-chip or microfluidic devices – that mimic cellular environments."
Ruder took this training and continued his scientific career as a postdoctoral research associate in Boston where he joined the lab of Jim Collins, PhD, a founder of synthetic biology. In Collins' lab, he learned to manipulate genetic circuitry to reprogram and put new functions into cells.
Ruder later received his first faculty position at Virginia Tech where he combined his research experience from Pittsburgh and Boston to pioneer the use of synthetic biology with robotics. His team engineered living bacteria to command and control a robot and mimic the connection between a gut microbiome and an animal host. They also engineered a nutrient-producing bacteria designed for an organ-on-a-chip system that mimics a gut.
After four years honing his research, Ruder decided to make a change and return to Pittsburgh.
"The University of Pittsburgh and its surrounding environment have allowed me to move from a focus on engineering bacteria, which has been straightforward for synthetic biologists for over a decade, to engineering mammalian cells," said Ruder. "Now, my lab is moving beyond engineering bacteria species that live in our guts and focusing on the actual human cells that make up our bodies."
This NIH-funded project combines the skills he learned in his previous training and appointments with the goal of reprogramming mammalian cell behavior, incorporating magnetics and magnetic field manipulation. "In this project, we will design and build mechanical protein scaffolds that will be inside of the cell, and upon application of a magnetic field, these scaffolds will morph and control the cell's behavior," explained Ruder.
An advantage to Ruder's strategy is that magnetic fields may be able to reach places that similar technology cannot. "A complimentary approach is optogenetics where researchers use light to manipulate cellular behavior," said Ruder. "One of the advantages of using a magnetic field, particularly if you can manage the challenge of concentrating it, is that it can penetrate the body where light may not be able.
"We hope to create structures that could regulate multiple downstream pathways, creating a new class of magnetically activated transcription factors as opposed to membrane-bound channels," said Ruder.
Ruder's short-term goal is to build the system and instrumentation for the project. His long-term, ultimate goal is to regulate a pathway and work with collaborators at Pitt to explore the effects of these tools on diseased organs, such as the heart or lungs. Ruder said, "We hope to make scientific discoveries and create technologies that can be applied to biomedical interventions and successfully regulate disease pathways."