Pitt researcher aims to develop 'smart biomaterials' for reprogramming mammalian cell signaling

Through a process called cell signaling, cells collaborate on necessary functions such as responding to changes in the environment, fighting off threats to the body, or regulating the basic processes that keep the body alive. Cells work much like computers carrying out functions and use cell signaling over a vast network. Also much like computers, cells can be reprogrammed to change their behavior.

Warren Ruder, assistant professor in the Department of Bioengineering at the University of Pittsburgh Swanson School of Engineering, is developing microparticles that carry engineered bacteria known as 'smart biomaterials.' As the basis of a study recently supported by the National Science Foundation, Dr. Ruder will use the biomaterials to reprogram mammalian cell signaling. The goal of the study is to use these hybrid, living-nonliving biomaterials to better understand how cell signaling works and influence cell behavior when a problem occurs.

"Fundamentally, many diseases result from incorrect cell signaling," explains Dr. Ruder, "which causes the body's natural control systems to fail to maintain normal function, or homeostasis. New tools that allow cell signaling to be rewired therefore can affect many diseases. This project is geared toward developing new tools for exploring and rewiring cell signaling."

Dr. Ruder will serve as principal investigator of the project titled "Creating Smart Biomaterials Using Engineered Bacteria that Cooperatively Reprogram Mammalian Cells." The research will focus on delivering synthetic genetic components to mammalian cells and reprogramming their calcium signaling processes, specifically. Calcium signaling occurs in many cells, and it controls both slow and fast cellular processes.

"Calcium signaling is one of the most important cell signals," Dr. Ruder says. "It is the signature of muscle contraction, relevant to many forms of cardiac or musculoskeletal disease, but also a master regulator of processes ranging from neuron firing and brain function to fertilization."

Once Dr. Ruder introduces the smart biomaterials, they will be able to collaborate and collectively determine when to transmit genetic components to mammalian cells. Dr. Ruder will then use mathematical modeling and computation simulation to explore the processes behind calcium signaling in mammalian cells and which genetic alterations will cause the most significant changes in cell signaling dynamics.

"The bacteria will be genetically engineered to invade mammalian cells. Once inside, they will genetically engineer the mammalian cells in a process distinctly different from viral genetic delivery. We will engineer two different types of bacteria that will signal each other and thus work as a team to invade after they monitor the environment," says Dr. Ruder.