Using Directed Evolution to Spur Innovation and Discovery

a screenshot with the words directed evolution

The Power of Technology in Bioengineering 

Technology plays a critical role in the success of bioengineering, an ever-evolving field in which scientists spend their time researching new ways to improve biology by leveraging principles of engineering. 

In some instances, bioengineering efforts can be lifesaving. This includes improving current medical procedures and propelling pharmaceutical research. 

But bioengineering is also used extensively in genetic research, including applications that involve evolution. Improved laboratory tools, such as automation, have propelled bioengineering and discovery in the realm of directed evolution, which is the subject of this blog. 

What is Directed Evolution and How is It Used? 

Directed evolution is a laboratory method that uses protein engineering to mimic natural selection. It is a core component of bioengineering. 

This is especially true in labs that conduct DNA shuffling, research new drug combinations, and work to speed up evolution in its natural state. This is often done by using a variety of lab tools such as automation and scanning systems. 

Though replicating natural evolution is impossible, these labs aim to pick and choose, or direct, evolutionary practices in ways that might improve future approaches to scientific research and medicine, even including surgical procedures. In some cases, directed evolution can also prevent time-consuming, inconvenient, or even risky outcomes, just like normal evolution would encounter. 

In a traditional sense, evolution refers to the incremental changes in an organism’s genetics over thousands of years of reproduction. Nowadays, evolution can technically occur in lab settings, too. By using the laboratory tools at their disposal, scientists are now able to speed up or even alter the evolutionary process on molecules, all within the lab. This operation is known as directed evolution. 

an image of lab pipettes being filled

By accelerating the evolutionary process, or in some cases, strategically altering it, laboratory teams aim to create new molecules such as proteins, antibodies, or enzymes. By doing this, scientists gain some control over the designated molecules and can monitor how and when they evolve. They then use this knowledge to further their research or continue with the directed evolution process, depending on what they are trying to achieve. 

In some instances, these scientists might even create antibodies to identify and potentially countermand certain cancerous or otherwise harmful proteins. Only through a process such as evolution, or in these cases, directed evolution, can some of these high-stakes, life sciences answers be found. And specifically with directed evolution, scientists can spot and then alter specified protein patterns to improve outcomes in a variety of ways. 

As we have seen, directed evolution is a powerful technology, and it has been instrumental in a diverse array of applications from cancer treatment to biofuels. It requires various tools, approaches, and technologies to be achieved, however, and that work typically starts in the lab. 

How Does Technology Allow Labs to Direct Evolution? 

Today’s biological laboratory relies heavily upon technology to successfully execute experiments, and those involved in directed evolution are no exception. Top-tier technology allows scientists to execute their workflows repeatably and reliably, obtaining quality data when they need it. These scientists must know how to operate such technologies, as well as consider their future applications and expansion. 

One of the major technological achievements in directed evolution occurred when Kevin Esvelt, a prominent Harvard University graduate and current MIT Media Lab Assistant Professor, developed a system to accelerate directed evolution. His process, known as phage-assisted continuous evolution (PACE), involves using bacteriophages to help proteins evolve towards a desired function, determined by the lab scientists. 

Using this continuous selection process, Esvelt was able to shorten the mutation round of a bacteriophage to 20 minutes. This also allowed the process to be repeated throughout the day, ultimately saving his team ample amounts of time to perform other tasks and conduct additional research. 

Over time, this method has been refined even further. PACE has changed the way scientists operate in the lab, as well as how they conduct their research. With PACE, scientists and researchers can be more selective in what proteins and molecules they target and how they target them. Some scientists even note this type of selective processing can be used in various health procedures, including intracellular therapy, when very specific cells must be targeted strategically. 

Aside from pushing health research forward, PACE has perhaps most notably enabled a speedier directed evolution, a scientific process that many people continue to study and expand. And with time arguably being one of the most valuable assets available, plenty of researchers and scientists vie for anything that will save them time. 

And not only did Esvelt’s process and bacteriophage experimentation help pave the way for improving direct evolution through this time-saving technology, but it also led to other individuals making new discoveries in the field. 

Emma Chory and the Next Generation of Directed Evolution 

Fast forward to February 2022, when Emma Chory, an MIT post-doctoral fellow, won the Society for Laboratory Automation and Screening (SLAS) Award for Innovation. The award, given to an “exceedingly innovative” research contribution, is highly honorable in laboratory and technology fields. 

Esvelt served as a senior author on the study alongside Chory, who received the award for her presentation entitled, “Phage and Robotics-Assisted Directed Evolution,” which focused on the directed evolution of biosynthetic pathways. 

Chory was one of ten participants in the 2022 competition. Her team consisted of five other co-authors, including Esvelt, who garnered knowledge from his previous experience with directed evolution, and contributed it to this project. 

Through her research and work, Chory discovered how to allow novel peptides to be synthesized in a way that could aid in the development of new treatments and therapeutics for a range of illnesses and medical conditions. 

Like Esvelt, Chory also prioritized improved speed in her processing, a theme that continues to stay important, especially in lab environments. She did so by co-creating and then using the Pyhamilton platform, a flexible type of lab automation platform, with her team. This platform allowed Chory and her team to advance the traditional lab application style to a more advanced approach. 

Through her research, Chory took previous directed evolution developments a step further by creating new experiments that would pose innovative questions about where to take the work next. Using the Pyhamilton platform, she and her colleagues did this by developing a technique known as phage and robotics-assisted near-continuous evolution (PRANCE). 

PRANCE enabled the team to “recapitulate” naturally occurring environmental changes and then simulate those changes to designated environments, a key step to the directed evolution process. The team was able to conduct this process in a lab setting, an accomplishment that ultimately garnered them the recognition of the SLAS via the Innovation Award. 

In an interview, Chory noted that her team’s research was about more than just saving time. She said that she hoped her award “inspired other basic scientists to tackle new (and old) questions from entirely different angles.” This includes questioning preconceived notions about evolution, and the belief that evolutionary fate is predetermined and that evolutionary outcomes are contingent on certain historical events, both of which relate heavily to health outcomes. 

Chory’s research findings also encouraged scientists to think more critically about evolution’s extremely specific impacts and what to do when it’s causing serious harm. And in turn, this would ideally motivate them to conduct new kinds of experiments that would potentially lead to critical answers to some of their most pressing scientific questions. 

In a separate interview, she talked about this in more depth by noting the ability of “tuning” these evolutions in real-time based on how well the evolutions occur. This success-determinant approach makes Chory’s discovery especially interesting. “We can tell when an experiment is succeeding, and we can change the environment,” Chory noted.  

Chory’s findings and encouragement to question current understandings of evolution brought to light the idea that asking more questions and probing more deeply are key to new discoveries in any field, but especially in the field of directed evolution. And in many cases, this approach can be applied to the use of laboratory technologies and tools, including those that are robotics-assisted. 

Robotics-Assisted Directed Evolution 

As laboratories grow more advanced, newer technologies and tools are becoming more widely available, helping further mature directed evolution as an application. One of these technological advancements is the development of a robotics-assisted directed evolution system. And one of the main advantages of this type of system is its efficient, time-saving capabilities. 

This robotics-assisted approach enables users to perform about 100 times as many directed evolution experiments as they could previously do. This is a major determining factor in how many lab scientists approach their research processes. This not only saves scientists and lab analysts time, effort, and money, but it also improves how they develop future lab techniques, and their very approach to evolutionary study. 

Additionally, saving time at this high of a level can increase and motivate the chances of scientists developing even more innovative and quick processes and approaches.  

Introducing automated workflows allowed scientists to perform directed evolution experiments on a far greater scale within their labs. Specifically, this automation lets lab analysts to work more efficiently, while gathering more information than ever before, all in less time, and it allows for additional scientists to join in helping with additional research and experimentation. 

This process and approach only help make Chory’s call to tackle both new and old questions alike more of a reality, as further automating biological processes with robotics accelerates her science. The extra time saved can now be used in data analysis or in the completion of other higher order tasks. 

Additionally, using robotics, scientists can automatically manipulate entire populations of bacteriophages or viruses, and then automatically generate reports on how any given experiment is performing. Thus, data from hundreds if not thousands of different evolutionary events may be obtained simultaneously. 

In turn, this creates space for the next generation of laboratory scientists to develop their own timesaving, lifechanging approaches to topics such as directed evolution. 

Robotics Assisted Direct Evolution and HighRes Biosolutions 

Robotic-assisted workflows are now common across the life sciences ecosystem. At HighRes Biosolutions, we offer a wide range of laboratory automation products and services that enable scientists to focus on and accelerate their scientific discoveries. 

One prominent example is our automated liquid handling instrumentation, which allows scientists to save space, time, and resources, ultimately garnering them unprecedented walk-away time. 

Our primary automated liquid handling workstation, Prime®, is loaded with performance capability within a design-forward, compact, and mobile footprint. With unique software that combines UI and intuitive method design, Prime is also extremely easy to use. 

It also comes with a built-in robot and ample storage space in the underdeck, which efficiently holds labware. Prime works in concert with other lab devices, making it an extremely versatile and functional tool. What’s more, the robotic arm and gripper capabilities of Prime ensure maximal functionality with minimal random-access limitations to its workspace. 

And, it is completely adaptable to different scientific approaches, tools, and docking systems, which makes for a highly versatile accompaniment to any lab. 

The robotics-assisted products offered by HighRes Biosolutions very well might see a future in the directed evolution space. This is true, particularly in labs that conduct several, often concurrent, experiments and that solely rely on such automation processes to do so. 

As a highly productive and innovative company, we prioritize improving human health through a variety of processes and approaches, including laboratory automation. We are proud to sponsor the SLAS Innovation Award that recognizes scientific leaders such as Emma Chory, and we are eager to see how she continues to sculpt directed evolution. 

We ourselves will continue to evolve laboratory automation and robotics to enable Emma, and others like her, to propel scientific discoveries such as that of directed evolution to greater heights. 

To learn more about HighRes Biosolutions and its offerings, visit our website. 

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