Engineering Life

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Biology and engineering are converging in an exciting, emerging field known as “synthetic biology.” Researchers are looking to harness the power of biologic systems – transforming and reprogramming cells – to perform new functions. These functions could translate into novel approaches for fighting disease, producing drugs, and even creating fuel sources.

Northwestern University will host a free event, “Engineering Life: A Synthetic Biology Primer,” on Tuesday May 10. We spoke with Michael Jewett and Joshua Leonard, speakers at the event and assistant professors of chemical and biological engineering at Northwestern’s McCormick School of Engineering, for a preview.

Joshua Leonard (left) and Michael Jewett (right) (Photo by Andrew Campbell)Joshua Leonard (left) and Michael Jewett (right) (Photo by Andrew Campbell)How would you define “synthetic biology”?
(JL) Synthetic biology is the effort to translate biology into a system in which we can do real engineering, so that we can harness the potential of living systems to address major societal needs, ranging from environmental stewardship and clean energy to new medicines and sustainable manufacturing. We’d like to get to a point where we can conceive of a function that we would like to perform (say, degradation of an environmental toxin), and then be able to design and build a biological system that carries out that function as predicted. Synthetic biology is the field seeking to achieve this goal.

(MJ) You can think of this like the engineering efforts in many other disciplines. For example, we’re fairly good at building bridges. If we want to design a bridge, we can put together the materials, the design, understand the physics of how it needs to go up, and the properties that make it stand and function. And what we’d like to be able to do is turn biology into a substrate that we can engineer akin to the bridges and mechanical systems we have today. Can we create an engineering discipline out of the science of biology where we easily transform and reprogram organisms to make targeted therapeutics that attack disease, to make food that feeds the world, and to make fuel for our cars?

(JL) A related and interesting question is: What’s new about synthetic biology – how does it relate to other approaches we’ve taken, and how is it different?  In my mind, a major distinction is that synthetic biology seeks to develop technology that allows us to build entirely new things. So it’s not simply a matter of retooling what exists, but being able to come up with completely new things that never existed before using a biological toolkit. An important part of what many people would consider synthetic biology is the idea that you can build these biological functions up from basic and interchangeable biological parts. Building these parts, characterizing them, and figuring out from an engineering standpoint how to assemble them so that they’ll work together in a way that’s predictable is a big part of what distinguishes synthetic biology from, for example, previous genetic engineering or metabolic engineering efforts. These technologies form the foundation of many things that we do in synthetic biology, but the way in which we use them is distinct in that way.

(MJ) Part of the challenge with learning how to predict and control biology is the fact that biology is unlike any other engineering discipline, because living systems have features that are distinct from the way that I might built a bridge. These systems evolve, they have noise, and they’re robust to local imperfections. For example, if you cut a wire in your computer, your computer probably isn’t going to work. But if you prick your finger, [that part of] your body heals [while] the rest of your body continues to function. So these features about biology make putting some user-defined objective into a cellular operating system really tricky.

Tell me more about how you might “transform and reprogram” an organism.
(MJ) Synthetic biology is arising out of our better understanding of the science of biology. That’s been built up even further by a confluence of technologies. The main ones that are driving synthetic biology right now have to do with the ability to read and write DNA, and at low cost. We not only understand what the genetic elements are of the cell that might do the things that we want to do, but we also have the ability to write pieces of DNA and create new languages inside of cells that carry out functions.

How are you using synthetic biology in your labs?
(JL) A major thrust in my group is developing human cell-based “devices”, which we can program to carry out custom functions for a variety of medical applications. We’re particularly interested in constructing cell-based therapies for treating chronic diseases by creating customized immune functions that complement and work with our body’s own natural defenses. We’ve turned to synthetic biology because it allows us to ask, “Wouldn’t it be nice if we had a cell that did this?” In other words, we can take our understanding of our own biology and use synthetic biology to implement therapeutic strategies that are far beyond the reach of pharmaceuticals and other current approaches.

A good example comes from our work in which we’re trying to treat cancer. Cancers are often long-term, evolving, chronic diseases, and one feature of many cancers is that the immune system becomes dysfunctional at the site of the tumor. This dysfunctional immune response creates a barrier to treatment and even promotes the growth of the tumor. Our current understanding is that throughout one’s life, a person probably gets occasional precancerous growths, but the immune system is able to control these. When this becomes disease, it’s often because the cancer has evolved the capacity to manipulate and suppress the immune response. The reason that this is problematic for treatment is that if you just try to boost the immune response, as we sometimes do now in the clinic, it doesn’t give the patient any real benefits, because the cancer has already figured out a way to deal with the immune system, to some extent.

What a synthetic biology approach lets us do is create cells that can be programmed to create novel immune functions, against which the tumor has not evolved resistance. For example, we’re programming cells to go throughout the body and patrol for signs of a tumor. Such an engineered cell essentially performs a logical evaluation of its environment and figures out exactly when it’s near a tumor and when it’s not. Then, only when it’s near a tumor, in a very specific and efficient fashion, it does something therapeutically useful. For example, the engineered cell could deliver a toxin, or it could initiate very potent immune activation right at that site, restoring effective immune function that clears the tumor. That would give us a way of attacking tumors wherever they happen to be inside of the body, and it should work for a wide variety of cancers. 

In this way, we consider the cell a device, which receives inputs, performs calculations on these inputs, and uses that information to decide whether to initiate some kind of action. The really exciting part is that if we can figure out how to do this for treating cancer, we can apply it to many other diseases, and even potentially flip the strategy and create immune functions that protect transplanted tissues or treat autoimmune disease. This is really the first step towards engineering our own biology for a variety of medical applications.

(MJ) We’re really interested in using biology to make stuff. In particular, we’re interested in using biology to make next-generation antibiotics that help us address rising anti-bacterial resistance, or cancer therapeutics, or even materials that self-heal. For instance, when you build a bridge, you [wouldn’t] have to reconstruct it later, because it [would] heal itself as it goes, like biological systems do. These are some of the kind of pie-in–the-sky frontiers that we’re looking into.

The reason we’ve centered in on biological systems is because biology is one of the best technologies we have for making molecules, making chemicals, and making therapeutics. However, engineering organisms as cell factories to make fuels and drugs is really tough.

One of the big challenges is that the cell has its own operating system, its own objective functions. Let’s say a cell’s objectives are to survive, to adapt, and to multiply. But I upload an engineer’s objective in the context of this cellular operating system. So you have this organism that is now undergoing a tug-of-war between the engineer’s objective and what it’s evolved to do over millions and millions of years. Rather than try to balance this tug-of-war, we actually try to focus biological systems on our own single objective by working with the hood up. My lab uses cell-free systems, or systems that allow us to exploit biology without using intact cells to make stuff. You can think of this like life without walls.  By stripping away the unnecessary complexity and DNA heritage that exists in cells, we can potentially activate and control biological systems in a much more efficient way. 

We’re doing this by focusing on protein synthesis and the ribosome.  The ribosome is the cell’s protein synthesis factory, and it is used in biotechnology to make the proteins for drugs and vaccines.  We’d like to learn how to construct and then retool the ribosome to make novel classes of drugs and materials that have been impractical—if not impossible—to produce by other means.

In biological systems, DNA is like a cookbook – this cookbook is transcribed into a recipe by a scribe, and then this recipe is translated into a functional protein. In this cooking analogy, the chef is the person who converts the recipe into a meal. In our case, the ribosome is the chef that converts the recipe into the functional output. What we’d like to do is teach the chef of the cell to make different types of meals.

Want to learn more about this exciting, emerging field? Join Jewett and Leonard at Engineering Life: A Synthetic Biology Primer, part of Northwestern University’s Biology by Design conference, on Tuesday May 10 from 6:30pm - 8:30pm. Admission is free and open to the public. For more information and to register, visit http://biologybydesign.northwestern.edu/.

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