We recently had the opportunity to speak with two remarkable professionals from Institut Curie, France's leading cancer research center. Dr. Leanne de Koning, Project Manager of the Single Cell Initiative, and Margot Le Bot, a PhD student in the Physics of Cells and Cancer Unit, shared their insights on how cutting-edge Live-seq technology is transforming their approach to understanding cancer at the cellular level.

Institut Curie combines an internationally renowned research center with a state-of-the-art hospital specialized in cancer treatment. The institute's commitment to innovation makes it the perfect environment for implementing novel technologies like FluidFM and Live-seq, which are opening new avenues for cancer research, particularly in understanding the complex dynamics of cell transitions in aggressive cancers.

The Single Cell Initiative: Bridging Expertise Gaps

The Single Cell Initiative at Institut Curie was created to address the complex challenges of single-cell and spatial omics technologies. "Single-cell and spatial omics are really complex technologies that require complementary expertise. You need cytometry, cell biology experts, molecular biology, sequencing, bioinformatics," explains Dr. de Koning. The initiative brings together four core facilities at Institut Curie that collaborate on these technologies, offering users a streamlined pipeline with a single point of contact.

"It facilitates access to these technologies for users and allows better coordination among different core facilities to make projects successful," says Dr. de Koning. The initiative leverages Institut Curie's diverse expertise, bringing together specialists in imaging, pathology, microfluidics, and other fields as needed.

Live-seq: A Complementary Discovery Tool

Institut Curie is among the first institutions implementing Live-seq technology, which allows researchers to follow the same living cell over time while studying its transcriptome at different time points. "Technologies like Live-seq allow us to offer capabilities that are not available in many institutes and that very well complement the other single-cell approaches we propose," says Dr. de Koning. "Many teams at Institut Curie work with live cell imaging to understand biological processes such as development, differentiation, migration, or physical confinement. Live-seq is of particular interest for those teams since it allows them to combine their live cell imaging with single-cell RNA sequencing over time from the same cell."

While Live-seq naturally operates at a more focused scale than high-throughput single-cell technologies, this is intrinsic to its unique capability to track individual cells’ transcriptome longitudinally. "I see it more as a discovery platform to define the genes and pathways of interest," explains Dr. de Koning. "It enables us to gather data that would be impossible to obtain otherwise, providing insights that can then guide more high-throughput approaches."

Tracking Cancer Cell Transitions in Real-Time: A Closer Look at Groundbreaking Research

Diving into the details of a cutting-edge project at Institut Curie reveals how Live-seq technology is being applied to solve complex biological puzzles. Margot Le Bot's PhD research focuses on epithelial-to-mesenchymal transition (EMT) in triple-negative breast cancer, a challenging cancer subtype with limited treatment options and high risk of metastasis formation. Breast cancer remains a significant health challenge, causing approximately 12,000 deaths per year in France alone (OECD’s 2023 report), with triple-negative being one of the most difficult subtypes to treat.

"Recent work in the field uncovered that there is a high heterogeneity among cells during the process of EMT, and this was done through single-cell technologies," explains Le Bot. When asked why her team chose Live-seq over traditional methods, Le Bot explains that previous work using classical single-cell technologies had already revealed EMT as a highly heterogeneous process with parallel pathway activations. "Therefore, following one cell through time and focusing on the transcriptomic changes happening in one cell through time is absolutely necessary to understand this process. It makes sense for it to be the next step to contribute to that field."

For Le Bot, FluidFM technology has become central to her daily work. "FluidFM is the main technology and methodology used for my PhD. On the day-to-day, that means that most experiments I perform are cell biopsy experiments or full life experiments."

Future Directions

Le Bot plans to expand her research to different solid tumors and study perturbations related to chemotherapies. "We know that the standard of care for most solid tumor cancers are chemotherapies, so it would be quite interesting to focus on the transcriptomic changes during chemotherapy," she says. She also hopes to tackle the mesenchymal-to-epithelial transition, which is less studied than EMT but as important for the formation of metastasis.

Both see significant opportunities for advancement in single-cell research over the next five years. Le Bot emphasizes the importance of better utilizing existing datasets: "A lot of data was produced in the last ten years, and I think we might be able to learn a lot from current datasets and then use single-cell technologies more efficiently."

Dr. de Koning looks forward to more multi-omics approaches that can provide integrated data on DNA, RNA, and protein levels. The FluidFM biopsy approach holds promise beyond RNA analysis, potentially extending to proteomics and metabolomics from the same living cell, creating opportunities to correlate transcriptomic and metabolic activity changes with protein expression in real-time. As awareness of Live-seq's unique capabilities grows within the scientific community, its adoption is expected to accelerate, particularly for research questions that benefit from tracking molecular changes in the same cell over time.

The Institut Curie Advantage

What makes Institut Curie uniquely positioned for implementing innovative platforms like Live-seq? The institute's environment fosters collaboration across disciplines and technologies. As Le Bot explains, "Being in the institute environment where there's a lot of cutting-edge research and a lot of people using state-of-the-art tools makes it very exciting to work together towards really state-of-the-art research."

Dr. de Koning adds that the Single Cell Initiative already has experience integrating a range of analytical approaches, from high-throughput standard approaches to more innovative, collaborative solutions. This existing framework makes it easier to incorporate new technologies like Live-seq.

Advice for Adopting Single-Cell Technologies

For researchers considering implementing single-cell technologies, Le Bot offers practical advice: "The most important and probably first step is talk to single-cell technologies experts and collaborate with them." She acknowledges the challenges of implementation while highlighting the value of community support: "Being in contact with other scientists and the [FluidFM] community of people working towards the same goal really helps manage challenges together and allows for rich exchanges."

As single-cell technologies evolve, Institut Curie's collaborative approach positions it at the forefront of cancer research. The successful implementation of FluidFM at Institut Curie has been supported by Cytosurge's responsive team. As Le Bot notes, "Working with Cytosurge has been very comfortable—their support service is there when problems arise, with answers to questions usually within a day." This partnership between research institutions and technology providers continues to drive innovation in cancer research.