LABBOT | Thom Leiding, CEO and founder of biotechnology company Labbot, gave an overview of the biological phenomenon, liquid-liquid phase separation (LLPS) at a GUMC event on August 29. LLPS, hypothesized to be a contributing factor to varied diseases, may prove critical in efforts to improve human health.
Thom Leiding, CEO and founder of Labbot, a biotechnology company, conducted a workshop on liquid-liquid phase separation (LLPS), a phenomenon thought to be the driving force for a myriad of diseases, at a Georgetown University Medical Center (GUMC) event titled “Continuous Tracking of Phase Separation and Aggregation” on Aug. 29.
LLPS refers to when a homogenous mixture spontaneously forms distinct layers, much like when oil separates from water. Scientists believe that LLPS could be occurring at a microscopic level within cells, making the cell much more dynamic than previously thought.
Cells contain organelles, which are self-contained units that help the cell carry out its functions. However, some proteins in the cell form small droplets, or condensates, that may also help the cell perform certain functions outside of the organelle. These temporary structures are thought to be the result of LLPS in action.
“We have all kinds of intermittent structures coming and going and doing their thing, and it’s like a zillion of them, and they are only there while they do their process,” Leiding said at the event.
The proteins that may drive condensate formation contain structural gray areas that researchers cannot easily identify using standard techniques, deemed intrinsically disordered regions. LLPS, a relatively new concept in cell biology, may hold the key to understanding the nuances of how proteins interact, according to event attendee Dr. Jeffrey Toretsky, chief of the division of pediatric hematology and oncology and director of the molecular oncology program at GUMC.
“As we try to understand how cells send signals within themselves, how they communicate with each other, we need to know how proteins interact with each other,” Toretsky told The Hoya. “And understanding liquid-liquid phase separation is now clearly identified as a critical method, a critical physiological phenomenon for how proteins interact.”
Toretsky has been studying LLPS in relation to its role in a type of childhood cancer called Ewing sarcoma for over two decades. Toretsky’s research team found that the main cancer-causing protein also has disordered regions, leading them to suspect that LLPS was playing a role in cancer progression.
“Understanding how the disordered protein interacts led us to liquid-liquid phase separation,” Toretsky said. “And that term and that concept really evolved over a 10 year period of time, again, as people were trying to understand how proteins interact. And in our case, we wanted to basically create a drug which would block those kinds of interactions.”
Apart from cancer, Leiding noted that LLPS may also contribute to the development of neurodegenerative diseases like Parkinson’s, Alzheimer’s and amyotrophic lateral sclerosis (ALS). Although the role of LLPS is still being investigated, it is known that abnormal protein interactions cause many diseases.
“It turns out that a lot of diseases are caused by proteins either interacting too much or not interacting enough, and sometimes the proteins even go on to change from a very flexible state to a very rigid state,” Toretsky said.
The question of how LLPS is involved in aging-related diseases like Alzheimer’s is the focus of Priyanka Joshi’s new research lab at GUMC. Joshi, an assistant professor in the department of biochemistry and molecular and cellular biology at GUMC and the event’s coordinator, explained that LLPS could be facilitating harmful protein interactions.
“LLPS may contribute to this process by creating sub-cellular environments where proteins are more likely to adopt aberrant conformations,” Joshi wrote to The Hoya.
This makes understanding the role of LLPS in cell functions especially relevant to those trying to develop therapeutic drugs for neurodegenerative diseases, according to Joshi.
“The precise understanding of these mechanisms is not just beneficial, but absolutely crucial for developing targeted, effective therapeutics that can truly make a difference in patients’ lives, potentially halting or even reversing the progression of these devastating diseases,” Joshi wrote.
Despite the promise that LLPS research holds, Toretsky said it is important to be aware that there is still much that is unknown about this phenomenon.
“I think that the whole field of liquid-liquid phase separation as a way of understanding biology is at its absolute infancy,” Toretsky said. “And it’s one of those areas that I think is going to be defining in terms of how we understand physiology, biology, and how we seek ways, namely, either drugs or other things, to alter it as a way to improve human health.”