How do cells differentiate? How do nervous systems evolve? And how can humans control these processes for our own benefit?
When it comes to the big questions in synbio, Harvard’s Weiss Institute for Biologically Inspired Engineering is a world leader.
Whether scouring the world’s oceans for exotic bacteria or replicating the origins of life, their researchers are famous for groundbreaking cross-disciplinary research.
Yet the organisation also has a deeply practical orientation, with research focused on solving the biggest problems in health and environment.
This applications-first approach is why so many projects at the institute have implications for biomanufacturing. Here, we cover ongoing research there laying the foundations of the future bioindustires.
CyanoPro: Sustainable biomanufacturing
The Wyss Institute’s Validation Projects exemplify the organisation’s commitment to technological utility. Selected each year, these are internal projects deemed by the institute to hold impact potential.
One of Wyss’ 14 Validation Projects for 2024-2025 was aimed squarely at the precision fermentation industry: CyanoPro.
Precision fermentation is the use of microbes to mass-produce chemicals or food. Often, it is more sustainable than conventional farming or chemical synthesis. Through the use of living creatures to ‘grow’ stuff, it minimises synthetic ingredients and processes.
Still, precision fermentation could be more sustainable than it is. Right now, for example, the process often relies on resource-intensive feedstocks like sugar to feed their industrial microbes.
CyanoPro is trying to cut sugar feedstock from precision fermentation altogether by using microbes that can feed entirely on gases – cyanobacteria.
The project got going in 2024, when Wyss researchers joined forces with a coalition of other scientists in an ocean expedition off the coast of Sicily. Their mission was to prospect for new cyanobacteria with potential industrial uses.
In volcanic seeps around the coast, they found a new species with all the features of a highly productive fermenter. Being 5 to 10 times larger than average microbial cells, the team nicknamed its novel microbe ‘Chonkus’.
Not only was its growth rate higher than that of other known cyanobacteria, Chonkus packs much more carbon into its body than existing strains. This makes it heavier and denser than other microbes – an unexpected plus from a commercial perspective.
Features like body density can make all the difference to cost: being heavy enough to fall to the bioreactor floor means Chonkus could be cheaper to collect and dry than lighter microbes that remain evenly dispersed through the medium.
On top of these natural advantages, researchers are going further by artificially modifying the microbe to ramp up efficiency.
Lead researcher for CyanoPro Elizabeth Hann is explicit in how her team’s science could reshape everyday lives: “Imagine driving past large pools where cyanobacteria grow, producing proteins that will eventually appear in the power bars you buy at convenience stores. Or, envision a simple device that allows you to produce all the food you need, with just renewable electricity.”
REFINE: better bioplastics
Wyss’ practical focus also comes through in its REFINE project. Led by Marika Ziesack, Emily Stoler, it is developing a scalable approach to make the bioplastic PHA.
Microbes are at the heart of this project too. PHA is a bioplastic made by microbes inside their bodies.
PHA is particularly useful in packaging. It can also be tweaked to display different physical properties for different applications, matching the versatility that makes petroleum feedstocks ideal for industrial use.
While PHA can do almost everything that ordinary plastics can, it has a crucial difference to fossil-based materials: it is able to biodegrade both in aerobic and anaerobic conditions.
Yet PHA production is expensive relative to the petroleum versions. They are even expensive relative to other bio-based materials, like those made from cellulose or starch.
At the REFINE project, the focus is on fine-tuning the PHA production process to achieve maximum cost efficiency. It is doing this by targeting multiple cost bottlenecks, chief among them oxygen transfer.
Oxygen transfer refers to the rate at which oxygen can move from the medium inside the bioreactor into the body of the microbes. This metric heavily influences how productive the microbes are.
Researchers found oxygen transfer is one of the major pitfalls in current PHA production after conducting a techno-economic analysis of biomanufacturing cost-drivers.
Nixe: Non-toxic raingear
The Wyss Institute’s Nixe project is aimed at tackling forever chemical (PFAS), toxic substances that have been widely used since the middle of the 20th century.
Forever chemicals last centuries in the environment, making them some of the most toxic residues of the modern world. Legislation is just now catching up decades of harm.
50% of global total PFAS use comes from making waterproof textiles. This overlooked source of pollution is often regarded as the final frontier for sustainable clothing manufacturing.
Today, many components of clothing can be made from eco-friendly bio-based alternatives. Yet outdoor wear manufacturers have struggled to find cheap and effective sustainable substitutes for forever chemicals when it comes to waterproofing.
After decades of PFAS-based rain gear, consumers have high performance expectations. Any new materials must match or exceed PFAS’ functionality to win market acceptance.
This is why Nixe has aimed at combining comfort, aesthetics, and functionality in their new PFAS-free coating.
Their silica-based chemical, for use on and within textile substrates, was developed with the Department of Textile Engineering, Chemistry, and Science at North Carolina State University.
Consumer perception shaped the design process for the coating from the start. It offers rain protection without impeding breathability and flexibility. Fabric drape and touch-feel were also factors taken into account.
The researchers melded functionality with comfort by studying the surfaces of the lotus leaf. At a microscopic level, the lotus leaf has features that trap air and repel water by turning it into droplets at the surface.
Apart from removing PFAS from manufacturing, researchers are trying to develop ways of removing them from the environment.
PFASense, another one of Wyss’ 2024-2025 Validation Projects, is using proteins to detect invisible forever chemicals outdoors. Right now, detecting PFAS means sending samples for costly lab-based procedures. Their portable bio-based detection system could lower the costs of finding the contaminant and getting remediation in motion much quicker.
Xenobots and autonomous cells: The stuff of life
Industrial biomanufacturing often relies on making fundamental scientific breakthroughs, like those coming out of Wyss’ xenobots programme – perhaps the strangest, most exciting synbio research project today.
Originally developed in 2020 from frog cells, these fully biological, self-organising robots have been at the centre of efforts to understand the most fundamental questions of life – how did movement, responsiveness, and purposiveness arise in animals?
The latest Xenobot experimentation has focused on the nervous system. Before now, the Xenobots moved and performed simple tasks. After adding precursor nerve cells into developing bots, researchers watched as the creatures grew out a complete primitive nervous system, all on their own.
The neurobots – what the researchers are calling the Xenobots imbued with nervous systems – moved more and in more complex patterns. Researchers are even observing signs in their genome that they could develop eyesight.
These animals are not just interesting from the perspective of evolutionary psychology. Lead researcher Michael Levin has described how the work has implications for neuroscience, the bioengineering of organs and tissues, and novel biological entities with programmable functions.
A similar research project recently brought Wyss researchers under George Church into collaboration with Chinese scientists.
The team investigated how we can genetically programme many cells to work together and do complex tasks autonomously – in other words, how to build complex, self-directed biological “machines”.
The research showed it’s possible to assign different chemical ‘tasks’ to cells as they multiply. An original “founder” cell is programmed to autonomously control what its descendant cells will do. This founder cell ‘knows’ how to generate a whole multicellular system, including how many cells of what kind it must produce.
Using this method, we can get large populations of cells interacting across multiple generations to achieve clear goals – just as they do in bodies and organs. Humans wouldn’t need to intervene at every step, however, since the founder cell is doing much of the work steering its descendants and their activities.
Like the Xenobot research, this type of work could open the door to new ‘living’ biomaterials that respond to environmental change and repair themselves like biological organisms.
With projects like this, the Wyss Institute is the cutting edge of synbio research today, proving that a focus on utility and commercialisation can spur scientific creativity rather than stifle it.
Central to its work is the notion that new biological insights can improve human lives and create sustainable abundance.
This intuition makes sense. By understanding nature deeply, we can get it to work for humanity more effectively. After all, many of the technical and economic issues that wrack the biobased industries be traced to a few fundamental questions: how does life work? Under what conditions does it thrive? And how do other organisms make sustainable use of their environments? These questions are the common concerns of both biology and biomanufacturing, life science and the bioeconomy.
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