Despite all that humankind has created, the natural engineering of biological systems never ceases to amaze. The human brain continues to outmatch manmade machines when it comes to pattern recognition: Finding the elusive “Where’s Waldo” is a breeze for us but not so much for artificial intelligence. And plants found in nature – simple organisms capable of making complex molecules – remain the basis for many drugs used today.
While drawing inspiration from “living” technology is far from new, building novel biological systems is here and now. An emerging discipline, synthetic biology brings together concepts from engineering, physics and computer science to create artificial biological processes to improve on nature’s original design. Much of the work in this fledgling field has centered on reprogramming cells by modifying their genetic code (or DNA) to serve specific purposes. Scientists are exploring innovative “synbio” processes that offer less expensive and faster methods for developing novel products, from environmentally-friendly fuel to reengineered immune cells that fight cancer.
The excitement of synthetic biology ‒ only a decade old ‒ has steadily mounted with advances in gene editing. Northwestern University has been an early force in this nascent field, with investigators in the Feinberg School of Medicine, McCormick School of Engineering and Weinberg College of Arts leading the charge. This year, the University took its commitment to a higher level by launching a new Center for Synthetic Biology. The Center will make Northwestern one of the top three U.S. destinations for research and education in this area, creating a much needed Midwestern hotspot for synthetic biology activity.
“The multidisciplinary nature of synthetic biology calls for an infrastructure to provide an intellectually vibrant ‘community’ where we can build critical mass and compete for large national projects,” says the Center’s director, Milan Mrksich, PhD, Henry Wade Rogers Professor of Biomedical Engineering, Chemistry and Cell and Molecular Biology. “This Center will be a place for us to recruit the best faculty, foster collaboration across campuses, encourage active exchanges with leading scientists from around the world and train students at all levels ‒ from undergraduate and medical students to postdoctoral fellows.”
Synthetic biology is a new enterprise where we are learning every day how to reprogram the living world in ways that benefit society.
The new Center’s faculty will double in the next several years. In the meantime, it will serve as home for the half dozen Northwestern researchers already making great strides in the field. For example, McCormick assistant professors Keith Tyo, PhD, and Joshua Leonard, PhD, are working on engineering yeast-based biosensors as inexpensive, easily accessible diagnostics for patients in resource-poor countries. Computational biologist Neda Bagheri, PhD, devises algorithms to map out cellular systems to better understand how mutations in genes or cells cause disease. This work could lead to more targeted therapeutic interventions.
“Synthetic biology is a new enterprise where we are learning every day how to reprogram the living world in ways that benefit society,” says Center co-director Mike Jewett, PhD, associate professor of Chemical and Biological Engineering “To that end, more than half of our work is focused on the medical arena: We’d like to impact that space with meaningful contributions.”
Accelerating Drug Discovery
The development of new medications often takes many years of trial and error before a drug ever reaches clinical testing. At the new Center, a rare combination of cutting-edge synthetic biology techniques and tools ‒ cell-free biosynthesis, high throughput compound screening and computational modeling ‒ has come together to significantly ramp up the drug discovery process.
The first part of the equation: Cell-free synthetic biology activates basic cellular processes without using live intact cells. Pioneers in cell-free in vitro translation, Jewett and colleagues were among the first to literally create proteins in test tubes. Gone are the limitations of needing to use live cells. This capability to liberally design cellular processes allows for on-demand production of 100s of enzymes a day that could more quickly point to promising drug candidates. Enter the second part of the equation: Mrksich joined Northwestern in 2011, bringing with him a high-tech tool he invented known as SAMDI (self-assembled monolayers desorption ionization). Contained within small thin metal plates, this technology allows researchers to cost-efficiently run more than 6,000 experiments an hour to measure enzyme reactions to new drug compounds. Investigators can also study protein function in organs to predict and detect disease. The third part of the equation: Predictive modeling helps to identify patterns in generated data to make the entire drug discovery process more efficient and effective.
“These approaches are revolutionary,” says Mrksich, who launched start-up company SAMDI Tech, Inc., five years ago. The contract research firm offers services using the proprietary technology to pharmaceutical and biotech clients. “Our leadership in these areas is unique to Northwestern and the centerpiece of our new Center.”
Building ‘Super’ Antibodies
Another biological wonder, the body’s immune system is a natural disease-fighting machine. It wards off microorganisms, from viruses to bacteria, by producing antibodies. Antibodies bind to specific proteins on harmful antigens and either disrupt the disease process or call in reinforcements such as white blood cells to dispense with the invaders.
Invented in 1975, manmade monoclonal antibodies (mAbs) were soon enlisted as soldiers in the war ‒ waged from the inside out ‒ against human disease. Designed for particular tasks, these antibodies could be programmed to direct the immune system into attacking specific “enemies” such as tumor cells. Today potent new mAb drugs are progressively becoming routine practice for treating cancer and immune system disorders. These antibody-based therapies are a high growth area, with rapidly increasing numbers of disease targets being added and tested in clinical trials. For synthetic biologists, the opportunity to engineer even more effective antibodies is too good to pass up.
Northwestern scientists currently have a patent application pending on new technology for developing “MegaMolecules” that boost the power of a type of antibody molecule called Immunoglobulin G. The typical Y-shape of this antibody dictates that it has two arms. Investigators in the Center for Synthetic Biology have come up with a way to make branched molecules with multiple arms: essentially more weapons to attack target antigens.
“Would you rather have an antibody with just a couple arms or many arms to go after cancer cells?” poses Mrksich, who is also associate director for research technology and infrastructure at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. “Not only do these MegaMolecules have the potential to speed up the immunotherapeutic response, but they may also be able to form more specific and tighter binding with their partner antigen for more effective treatment.” Testing in animal models has yielded strong results, showing that the MegaMolecules are active and working as intended.
Souped-up antibodies are just one of many technologies imagined and brought to life by synthetic biology innovations. With the establishment of the new Center, the possibilities for developing novel therapies and transforming care are endless. Mrksich’s leadership within both the Center for Synthetic Biology and the Lurie Cancer Center, in particular, will allow for close collaboration and, ultimately, acceleration of groundbreaking cancer therapies.
“The aims of the new Center will have a tremendous impact on how we develop novel therapies for our cancer patients,” says Leonidas Platanias, MD, PhD, director of the Lurie Cancer Center. “The novel biological systems and data the synthetic biologists generate will make a big difference in building the foundation of our cancer research and treatment. The Center for Synthetic Biology is a very good match for our efforts.”