The Fungal Network: Syncytia are Integral to understanding Life

The Fungal Network

Syncytia are integral to understanding life

By Jasmeet Singh

Image by USCDCP. [CC0]

Imagine this: You are walking through the forest when cells such as cancer and SARS-CoV-2 (the virus responsible you stumble upon a patch of toadstools. Even though for COVID-19), and more.1 you cannot hear them, these organisms chat with count- You may be asking, why cells? Dr. Gladfelter explains less other species via a web of branched out multinucle- that examining cells at the microscopic level is intuitive ated cells known as syncytia. By transmitting information for her. “There’s people that study elephants,” she says, to trees that appear far out of reach and communicating “and that’s their scale. And then there’s people who with bacterial colonies deep inside the soil, fungi effectively bridge the “By understanding the study galaxies. I like thinking about problems at the scale of a cell.” gaps between ecosystems. It is no biophysics of the processes Studying live fungi with fluorescent wonder they are thought of as “the Earth’s internet.”1 inside these structural units, a microscopy provides one such approach, as most fungi are giant Dr. Amy Gladfelter, a professor new world and perspective can fused cells that house many nuclei of cell biology at UNC-Chapel Hill, be unlocked.” — and thus, many genomes — uses this example to illustrate the bathed in the same cytoplasm. importance of her work with While it is not yet understood why fungal cells take fungal syncytia in an effort to on this form, their unusual structure fascinates researchers. understand cell organization. Fungi take on shapes ranging from branched to sporous, Her lab is conducting a multitude and the organelles inside their cells constantly perform of research projects at any given a myriad of actions. This may sound like chaos. However, moment, projects that span the Gladfelter lab is able to pry open cells, look at their human and environmental individual components, and understand this complex bodies. The applications of system in a simpler fashion. Thus, the inner workings of this research could provide fungal cells become ordered chaos as Dr. Gladfelter and the pathway to understanding her team investigate the cell’s governing rules and overall integral components of the organization.1 biosphere, neurodegenerative One mechanism that Dr. Gladfelter’s research has

Dr. Amy Gladfelter diseases, the science of syncytial explored involves the ways in which cells create functionally

Carolina Scientific life science distinct areas. Proteins undergo phase separation in a manner similar to a water molecule changing from a liquid to a solid and vice versa. Contained in droplets defined as “condensates” inside the cells, proteins are part of a phenomenon which differs from the usual membraneenclosed, compartmentalized organelles. Also residing in the droplets are RNA (short for ribonucleic acid, which assumes a fundamental role in gene regulation and coding) and mRNA (messenger ribonucleic acid, which carries genetic information from the nucleus to proteingenerating complexes in the cytoplasm). By inspecting the RNA-binding protein (RBP) Whi3, another study in which Dr. Gladfelter is involved proposes the following: each condensate is kept separate due to components of the RNA that dictate the particular properties of the condensates formed by Whi3.1,2 These findings could be monumental in understanding how information is organized within these condensates. Although the Gladfelter lab concentrates more on research at the cellular level, its applications could prove monumental. For example, an amalgamation of fungi, protein, and condensate data can be applied to neurodegenerative diseases. Droplet formation is part of normal cell function. When mutation and aging occur as a result of oxidative stress, however, toxic aggregates form in place of the droplets, and phase separation halts so that the condensates exist in a perpetually solid-like state. The loss of the droplets’ dynamic properties characterizes neurodegeneration. This can be seen in a recent discovery which describes that “proteins linked to [amyotrophic lateral sclerosis (ALS)] form condensates, and mutations in these proteins can make the condensates more viscous than usual.”3 Condensates are also said to be linked with other neurodegenerative diseases such as Alzheimer’s and Huntington’s. Additionally, cancer, SARS-CoV-2, HIV, and human orthopneumovirus all cause cells to become syncytial. While the Gladfelter lab and the greater science community are not yet certain of the reason cells adopt this form, it certainly holds significant relevance to their field. Alongside its very topical SARS-CoV-2 research, the Gladfelter lab is currently engaged in a project about a cell (the syncytiotrophoblast) that covers the entire placenta. The syncytiotrophoblast provides a barrier between the mother and the fetus, secretes hormones, and controls a number of metabolic functions. Though captivating in its own right, its prospective relevance to women and

Figure 1. Syncytial cell under a microscope. Syncytia are unique because they are giant, multinucleated cells. Image courtesy of Wikimedia Commons children’s health is a significant development.

Figure 2. Fibrillarin is an example of an RNA-binding protein. These proteins bind to the RNA in cells and play an important role in the transcription, translation, and regulation of gene expression. Image courtesy of Wikimedia

Commons Dr. Gladfelter’s work with fungi and other syncytial cells takes on a level of complexity that causes it to be sometimes underappreciated. Of course, the applications of these studies are acknowledged for good reason: many people are primarily interested in large-scale ideas. But by understanding the biophysics of the processes inside these structural units, a new world and perspective can be unlocked. For researchers, this means more investment of time and money into investigating syncytial cells and gaining a steady grasp on how cells are organized. This knowledge could then be utilized in conceptualizing the inner structure of condensates, shedding more light on how neurodegenerative diseases work and possibly even precipitating the race for a cure. Just as the future of humanity lies in technology, it is also deeply rooted in fungi.

References

1. Interview with Amy Gladfelter, Ph.D. 09/11/20. 2. Langdon, E.M.; Qui, Yupeng; Niaki, A.G.; McLaughlin,

G.A.; Weidmann, C.A.; Gerbich, T.M.; Smith, J.A.; Crutchley,

J.M.; Termini, C.M.; Gladfelter A.S., et al. Science. 2018, 360, 922-927. 3. Bayer makes first move into condensates. Nat Biotechnol 38, 5 (2020). https://doi.org/10.1038/s41587-019-0386-6 (accessed September 16th, 2020). 43