Exploring New Biological Frontiers with LSD1

Our journey began with a novel approach to identify coregulators of the transcriptional regulator LSD1, an important player in gene expression. By coupling a fluorescent reporter system to monitor LSD1’s activity combined with an unbiased, multiplexed screening approach, we generated an extensive list of potential candidates. While promising, this list was daunting, as many of the hits were outside our primary research expertise. Initially, we were uncertain if any would reveal relevant biology.

However, our prior experience taught us that this approach could yield significant discoveries. In 2021, we successfully published insights on an unexpected LSD1 coregulator in Nucleic Acids Research (Pinter et al., 2021). Inspired by this success, we set our sights on another candidate: NEK6, a kinase with no previously known role in LSD1 biology. This led us to take on an ambitious project, one that required developing every aspect from scratch.

Entering Uncharted Territory

To our surprise this project led us into the field of biomolecular condensation at an early time point. Our lab is relatively new to the world of phase separation research, and we quickly realized that a significant aspect of the project would involve establishing all the necessary experiments from scratch. From constructing assays to optimizing protocols, we built a foundation step-by-step, facing the learning curve head-on. As with any emerging field, expertise and methodologies are still evolving, which made our entry both exciting and overwhelming.

Building from the Ground Up

Setting up experiments in a new domain requires time and precision. Every technique, piece of equipment, and experimental approach we adopted came with a series of learning trials. Being a small lab meant that we didn’t always have immediate access to specialized equipment or an established body of protocols to guide us. Instead, we relied on creativity to develop a cohesive approach from the ground up.

One memorable day, the air conditioning unit was overwhelmed by the continuous hot weather, leading to an unexpected crisis: water began dripping all over the confocal microscope setup—a key piece of equipment for our work. Unfortunately, the water was recognized once it found its way all over the whole machine down to the computer, so we were not sure about the damage extend. In the end, we gathered everything together, removed the water and the electricity and dried the microscope. Luckily, the damage was minor, but the samples of that day were gone and the next appointment could only be scheduled 6 weeks later. Despite such hurdles, we managed to keep moving forward, reinforcing our commitment to seeing this project through.

Adapting in a Rapidly Changing Field

Biomolecular phase separation is currently one of the fastest-developing areas of cell biology. What was considered a "standard method" one year was updated or even overturned the next. As new discoveries were published, we found ourselves needing to modify our experiments to stay aligned with the current understanding. This wasn’t just a minor adjustment—it often meant revisiting, amending, or repeating work that had taken us months to perfect.

A Lengthy Journey, but a Worthwhile One

In the end, this project took longer than we had initially planned, primarily due to the rapid advances in the field and the repeated fine-tuning required. However, this longer timeline also allowed us to make meaningful adjustments, yielding a robust and comprehensive study that we’re excited to share with the community.

Working in a small lab, new to the field, and with limited resources pushed us to grow as scientists and problem-solvers. We hope our work contributes valuable insights and paves the way for others navigating the challenges of phase separation research. We’re proud of this paper, not just for the results but for the resilience, adaptability, and teamwork that brought it to life.