Recent findings through a collaboration of Lawrence Berkeley National Lab (LBNL), researchers from the U.S. Department of Energy Joint Genome Institute (JGI), and the Technical University of Munich have uncovered new methods for creating advanced bio-products through the study of fungi. The team at Berkeley Lab is led by former Energy & Biosciences Institute researcher, Louise Glass, who has a connection to the study of fungi that dates back to the early days of the EBI. We sat down with Louise to discuss her research and how it impacts science and industry.
During the early years of the EBI, Louise’s interests were already turned to a model filamentous fungus as opposed to industrial relevant fungus types. She wanted to understand how the Neurospora fungus breaks down plant cell walls into sugars. Louise remembers, “Many of the tools were not available for studying industrial fungi. But those fungi were closely enough related to Neurospora that we felt we could extend those concepts and even those tools and genes involved in those processes to other fungi. And that turned out to be spectacularly successful!” Neurospora works in nature to break down the cell walls of dead plant material. Louise relates that if you’ve ever been in an area such as Lake Tahoe after a wild fire and noticed orange coloration in the burnt trees, you’re witnessing Neurospora in bloom. This specific fungus has been vital in understanding basic concepts of biology and genetics. Louise lists a few of the common uses within the field of biology, “Circadian rhythms, one gene one enzyme, epigenetic mechanisms, and most recently on how codon usage affects translations. So it’s been used in textbook cases of biology.” She explains that even though these uses were detected as far back as the 70s, the field of study and application swayed towards use of Trichoderma which became the “workhorse” of the biotechnology field. Louise describes her initial research with the EBI, “So as part of the EBI, we had three goals. The first was to understand the regulatory network of carbon, nitrogen, and phosphorus utilization in Neurospora… allowing them to use plant biomass and produce enzymes. It’s always a very elegant tradeoff between what’s used and what’s made. If you understand that then you can manipulate the system to make whatever you want.” The team additionally worked towards defining a proof of principle for using this process to produce enzymes and proteins as well as identify viable industrial uses for using it in the production of Bioproducts.
In their research, Louise’s team soon discovered a new transcription factor that regulates most of the cellulase – the enzymes that catalyze cellulose decomposition – genes encoded in the Neuospora genome. This creates the potential to produce these enzymes independent of plant cell wall material that would naturally induce production. Louise explains the importance of this finding, “That’s very useful for industry because you don’t have to worry about adding an inducer. It was a proof of principle of how using a model organism can very rapidly delineate important nodes of this regulatory network that can then be manipulated… for biofuels and bio-products.” Louise and her team subsequently patented the resulting technology through the EBI.
The team’s recent paper is a culmination of Louise’s prior research coordinated with a look into the global carbon regulatory network that has been able to determine new roles for a transcription factor that was not previously appreciated for its usefulness. Louise explains, “Through that global analysis we identified a role for PRE-1, a very well characterized transcriptional repressor. We now understand how we can manipulate it to cause repression of these enzymes. It’s sort of the Yin and Yang. You have things that activate and you have things that repress. And if you understand how that repression works then you can eliminate that to produce even more protein.” Louise’s group currently has another paper under review that examines the nitrogen regulatory network in the same fashion. She elaborates, “You can’t live on carbon alone. You have to have these other major nutrient sources. We’ve often wondered what the interplay is between nitrogen and carbon utilization so the second paper focuses on that interplay between carbon and nitrogen regulation and how the organism manipulates both of those regulatory networks so that it can make the optimal enzymes without, for example, running out of nitrogen.” Louise praises the EBI’s first director, Chris Somerville, for playing a key role in obtaining funding and support for her initial projects that led to her findings.
According to Louise, this research stands to primarily impact the biotechnology industry. She explains that, “These industrial organisms, filamentous fungi, pump out a ton of protein. It’s then used to make a bunch of different things.” Some of her research associates provide a simple example in the work they do within their company, Perfect Day, using filamentous fungi to produce proteins to make non-dairy ice cream. Louise continues, “So it’s important in the food industry. It’s important in textiles. There are companies that again make proteins in this filamentous fungi that then are used for making thread similar to spider silk. There are other companies that have used these organisms to express antibodies. So they’ve been really used across the board primarily for protein production.” She explains that in fact much of the research on filamentous fungi was initially applied to the textile industry. Many of the enzymes found in common laundry detergent are often derived from factories that utilize these fungi to produce them. That technology went on to be adapted to the biotechnology field and the biofuel field after that. With such a widening array of uses, this technology has become vital to certain companies. Louise elaborates, “I think there’s many many different applications and a little bit of extra protein in these companies can either make or break them. So anything that you can tweak to get higher protein production… that’s going to help your bottom line.”
Since 2017, Louise has obtained funding outside of the EBI through NIH, BASF, as well as funding through the Fred Dickinson Chair of Wood Science and Technology in a sort of shift to medical applications of her team’s research. She maintains optimism for the potential to work through the EBI for her research in the future.
Find out more about Louise’s current research here!