Our Research

Cell-Free Biomanufacturing

Cell-free biomanufacturing provides an unprecedented freedom to modify and control biological systems

Biomanufacturing allows for agility and diversity that cannot be achieved in traditional petrochemical production. However, a key challenge is that nearly all current investments in biomanufacturing are based on production using cells. While traditional biotechnology approaches have delivered impressive outcomes (e.g., human insulin), the use of cells to produce products remains costly, risky, and slow. This is because cells themselves impose inherent limitations on the effective production and release of biobased products. Such constraints arise from the fact that cell survival objectives are often diametrically opposed to the objectives of bioengineers. This leads to a variety of common challenges afflicting the current state-of-the-art: low product yields, product toxicity, limited chemical palette of potential products, and physical barriers (i.e., the cell wall) that limit sample acquisition, monitoring, and direct control. On top of this, the current centralized manufacturing approach limits biomanufacturing potential because of the expense and time required to build large facilities and the common requirement to use refrigerated supply chains.

To address current capability gaps, new tools and approaches are needed to derive general paradigms that can be implemented to:

1. Scale biomanufacturing platforms to satisfy increased demand;
2. Advance point-of-need, decentralized manufacturing for decreased logistic demand and secure supply chain; and
3. Synthesize advanced functional materials (e.g., personal protective gear) and rapid, inexpensive, and portable sensors for intelligence, surveillance and reconnaissance and human performance applications.

Cell-free systems are emerging as a powerful new tool to meet this need. Cell-free biomanufacturing is a significant departure from traditional, cell-based processes that rely on microscopic cellular ‘reactors,’ providing an unprecedented freedom to modify and control biological systems. Compared to cells, cell-free systems:

• require less development time to go from concept to production
• scale linearly from microliters to thousands of liters
• provide an increased rate of molecule production
• do not require the removal of products from cells
• are tolerant to high levels of toxic products
• unlock novel opportunities for on-demand manufacturing at the point-of-need

Northwestern University has established a basic science research institute, the Cell-Free Biomanufacturing Institute, in partnership with the U.S. Army. Its goal is to accelerate the development of synthetic biology technologies for the creation of on-demand and point-of-need products useful to both society and the Army.

Synthetic Biological Materials

Synthetic biological materials expands the scope of traditional materials science

At the forefront of innovation, we are developing novel synthetic biological materials, driven by the exploration of biomaterial properties using intricate biological components. Our investigations extend to various avenues, including the study of bacterial micro-compartments, artificial cells, and liposomes, which allow us to unlock unprecedented insights into the fabrication of tailored biomaterials. Employing cutting-edge techniques in materials characterization and leveraging the power of computational modeling, we delve into the atomic and molecular scales to elucidate the behavior and interactions of these biomaterials. This multidisciplinary approach not only expands the frontiers of synthetic biology but also has the potential to transform industries ranging from medicine and biotechnology to materials science and beyond, paving the way for the creation of advanced, functional materials with a broad spectrum of applications.

We aim to establish the science, technology, ecosystem, and workforce necessary to rationally engineer biological materials with precise control over structure and functional properties. To achieve this goal, we are establishing a general framework that integrates predictive modeling, artificial intelligence, rapid synthesis via cell-free systems, high-throughput characterization, and scale-up of materials production for evaluation and prototyping. Our strategy will enable model-based connections between biomaterial composition and properties in a rational manner. A key emphasis of our approach is the integration of biotic and abiotic interfaces, which will enable synthetic biology materials to be fused with and expand the scope of traditional materials science.

Synthetic Immunology

Synthetic immunology represents a paradigm shift in the way we approach immune-related complexities

By integrating principles from immunology, genetics, and engineering, this interdisciplinary field empowers us to design immune systems with enhanced precision and effectiveness. From engineering immune cells to target specific pathogens or tumors, to developing synthetic vaccines that offer rapid response to emerging diseases, synthetic immunology has the potential to reshape the landscape of healthcare. Furthermore, this field opens doors to innovative therapies that modulate immune responses, potentially offering relief to those with autoimmune disorders or graft-versus-host complications. As we unravel the intricate interplay between immune cells, signaling pathways, and molecular interactions, synthetic immunology not only advances scientific understanding but also paves the way for revolutionary medical interventions that could transform the lives of countless individuals.

Sustainable Biochemical Production

Sustainable Biochemical Production

Biosensors and Diagnostics

Biosensors and Diagnostics

Rapid, on-demand, and portable monitoring of chemicals in water supplies, or human performance biomarkers in biological samples, is a vital capability. Synthetic biology offers technological breakthroughs with potential to transform sensing systems. One key breakthrough has been the creation of freeze-dried, field-deployable cell-free platforms that produce detectable signals when rehydrated with a sample that contains a specific chemical or biomarker target. At the core of these platforms are genetically encoded factors that bind to chemical markers and trigger changes in reporter gene expression to generate a visible output. We are building out this technology for the implementation of new schemes for molecular detection.

This research will lead to new fundamental knowledge and transformative applications. We are learning new design rules for biosensing by screening thousands of factors from a broad phylogeny of microbes. By constructing synthetic systems whose function links traditional concepts of protein-ligand interactions with the principles of enzyme chemistry, we may uncover new understanding of the optimal biosensing properties for detecting various classes of analytes. In addition, the experimental pipelines that we are establishing to link the genetic sequence of a given biosensor variant to its corresponding sensory properties (e.g., limits of detection, dynamic range) will be of great utility for the design and optimization of new biosensors for practical goals of environmental monitoring and human performance.

Human Therapeutics

Human Therapeutics

Model-Informed Design

Model-Informed Design

High-throughput Discovery

High-throughput Discovery

Educational Tools

Educational Tools

Recent advances in synthetic biology have resulted in biological technologies with the potential to reshape the way we understand and treat human disease. Educating students about the biology and ethics underpinning these technologies is critical to empower them to make informed future policy decisions regarding their use and to inspire the next generation of synthetic biologists. However, hands-on, educational activities that convey emerging synthetic biology topics can be difficult to implement due to the expensive equipment and expertise required to grow living cells.

To address these issues, we have adapted synthetic biology lab activities into two portable, low-cost, and user-friendly educational kits: BioBits Bright and BioBits Explorer. These kits are made possible through the use of freeze-dried cell-free technology. We are creating new modules to teach biology and synthetic biology concepts.