Systems and Synthetic Biology
We investigate the principles governing the design of living organisms. Recent technological advances are revealing not only the blueprint for life but also providing the means for rewriting it. We are fast approaching the point where biological systems can be exploited as entirely new programmable material – one that can also reproduce, heal, and evolve. The potential applications of engineered biological systems are limitless and intersect with many key challenges facing humanity, including food, health, energy, and the environment. The challenge is that we still do not know the “grammar” of life. Our goal is to decipher it.
We are pursuing a number of projects at the interface of systems and synthetic biology. Our approach is to reverse-engineer natural systems that exhibit interesting properties and then apply this knowledge to design synthetic systems for various applications. In addition, we apply design to teach us about biology, where we build synthetic analogues of natural systems to identify their essential components. Concurrent with the efforts, we develop computational and experimental tools to aid the design and interrogation of biological systems. Our main efforts are listed below.
All organisms must respond to their environment. The world is not static and, unless an organism can adapt to change, it risks death and ultimate extinction. Prominent examples include the ability to adapt to nutrient depletion or toxin influx. At the heart of any adaptation mechanism, irrespective of the organism or habitat is the ability to sense environmental changes and act upon them. We investigate the complex mechanisms that enable bacteria to sense and respond to their environment. Examples of systems studied in our lab include nutrient sensing, foraging, antibiotic resistance, stress to aromatic compounds, and host colonization (in the context of infectious diseases). Our goal in studying these systems is not solely to advance biology but ultimately to reprogram this behavior for the treatment of disease and production of novel chemicals.
Tools for the rational design of living organisms
We develop computational tools to enable the rational engineering of living organisms. Despite tremendous progress in synthetic biology, the design still involves significant trial-and-error and lacks the principles found in other engineering disciplines. Past efforts have focused on the rational design of genetic components. Current efforts are focused on identifying novel routes for chemical production and global strategies for organism engineering. In addition, we are creating computational tools that enable the rapid prototyping and design of living organisms. These tools exploit recent advances in robotics, including the autonomous system that a group of us developed recently at Illinois.
Engineering non-model organisms
We are still limited in our ability to genetically engineer many organisms. Most work to date has focused on a few model organisms where genetic tools are readily available. However, these model organisms lack many desirable properties such as the ability to survive at high temperatures or grow on complex carbon sources. In addition, their metabolism is often not sufficiently flexible to produce many chemicals and materials of interest. We are developing new genetic tools for engineering non-model organisms. In addition, we are domesticating these organisms for the industrial-scale production of chemicals and fuels.
Biomass to chemical and fuels
Many projects in our lab are ultimately focused on producing chemicals and fuels from plant biomass. Both terrestrial and aquatic biomass provides a renewable and carbon-neutral source for chemical and fuels. Our current efforts are focused on engineering non-model organisms for the production of chemicals and fuels, and exploring the physiology of marine microorganisms for the use of aquatic biomass as alternate feedback to terrestrial biomass. In addition, we are investigating how the global physiology of an organism changes when it is engineered to produce an unnatural chemical or fuel.
Our work employs a combination of experimental, computational, and theoretical techniques. We are problem-focused, and our general strategy is to employ and develop techniques that best enable us to solve our problems. Examples to date range from genetics, biochemistry, mass spectrometry, microscopy, and NMR on the experimental side to bioinformatics, finite element analysis, molecular dynamics, and stochastic and multi-scale simulation on the modeling/theory side.