We had the pleasure of meeting Meryem, who shared her journey with us and presented the results she obtained thanks to this visit.

Could you introduce yourself?

I am originally from Agadir, a coastal city in southern Morocco, where my curiosity about the living world began long before I knew it had a name. What fascinated me from the start, and still does, is the paradox at the heart of immunity: the same system must defend us against pathogens without ever turning against our own tissues. That question brought me to France, where I studied immunology and completed my PhD in Immunology at Université Paris Diderot.

During my PhD, carried out in Professor Renato Monteiro’s laboratory, I investigated Fc receptors and uncovered unexpected mechanisms regulating antibody-mediated immune responses. Our work challenged the traditional view of these receptors as purely activating molecules, revealing that the very same receptors can either amplify or restrain immune responses depending on the biological context. This work highlighted the remarkable adaptability of the immune system and its ability to fine-tune inflammation.

After completing my PhD, I joined the Centre de Physiopathologie de Toulouse Purpan (CPTP) in Toulouse in the laboratory of Dr. Nicolas Fazilleau. There, I turned to the regulation of humoral immunity, where our work revealed an unexpected heterogeneity within follicular regulatory T (Tfr) cells, reshaping our understanding of their role in regulating germinal center responses.

To further broaden my expertise, I spent two years as a visiting researcher in Professor Adrian Liston’s laboratory at the University of Cambridge. I was fascinated by the way Adrian had built his laboratory around a truly interdisciplinary vision, bringing together immunologists, molecular biologists, computational biologists, mathematicians, clinicians… to tackle fundamental questions of immune regulation. Working in this environment transformed the way I approach scientific research and convinced me that the most exciting biological discoveries emerge at the interface of multiple disciplines.

Today, I am an INSERM scientist at the Toulouse Institute for Infectious and Inflammatory Diseases (INFINITy), where I have established an independent research program investigating how regulatory T cells orchestrate T–B cell cooperation in health and disease. My goal is twofold: to uncover the mechanisms that govern protective immunity, and to identify biomarkers that improve immune monitoring in vaccination, autoimmune disease, and cancer. To achieve this, I combine fundamental immunology with emerging technologies and translational research.

What is your research project about?

The nucleus is much more than a container for DNA. It is closer to a library: the way the books are arranged on the shelves determines which ones can be read. And in immune cells, we have barely started to look at the shelves

Regulatory T cells are essential for maintaining immune homeostasis. Far from being mere suppressors, they actively orchestrate interactions among T cells, B cells, and dendritic cells to ensure that effective immune responses develop while preventing excessive inflammation and autoimmunity.

Although decades of research have identified the molecular and epigenetic programs controlling regulatory T cells, we still know remarkably little about how the three-dimensional organization of the nucleus contributes to establishing and maintaining their identity.

The spatial organization of chromatin determines which genes are accessible, how they are expressed, and ultimately how a cell acquires its function. Yet this level of regulation remains largely unexplored in regulatory T cells.

To investigate this, we use two complementary populations as experimental models: CD4⁺ and CD8⁺ regulatory T cells. Our previous work revealed important molecular differences between them, leading us to hypothesize that they may also possess distinct nuclear architectures.

Ultimately, we aim to determine whether nuclear architecture represents an additional layer of immune-cell organization that shapes immune-cell function.

You received financial support to access a France-BioImaging facility. Which facility did you visit, and which imaging technology did you use?

I first heard about France-BioImaging through our imaging facility, and the User Access call arrived exactly when our project needed a technology we did not have in Toulouse.

Through the France-BioImaging User Access program, I obtained access to the imaging facility at the Institut de Biologie de l’École Normale Supérieure (IBENS) in Paris.

The project is carried out in close collaboration with Dr. Samira Bennada, Head of the IBENS Imaging Facility, whose expertise in expansion microscopy and quantitative imaging has been instrumental in shaping both experimental design and imaging strategy.

Expansion microscopy relies on a counterintuitive idea: rather than relying solely on a more powerful microscope, the biological specimen itself is physically enlarged. The sample is embedded in a swellable polymer, where molecular labels are anchored before controlled expansion physically separates them while preserving their relative organization.

In our protocol, the sample is physically expanded before imaging, increasing the effective imaging resolution and allowing quantitative visualization of nuclear structures that were previously below the diffraction limit (Figure 1).

Our project combines expansion microscopy with two complementary imaging modalities: the NSPARC detector for high-resolution confocal imaging of chromatin-associated markers and nuclear compartments, and spinning-disk SoRa microscopy for rapid three-dimensional super-resolution imaging.

Together, these approaches provide a multiscale quantitative imaging pipeline adapted to investigating the nuclear architecture of rare primary regulatory T cells.

Why was this technology relevant or essential for your research project?

Current molecular and genomic approaches have transformed our understanding of regulatory T-cell biology by identifying the genes, transcription factors, and epigenetic programs that define these cells. However, they provide little information about how these molecular components are spatially organized within the nucleus.

Yet, the three-dimensional organization of chromatin is increasingly recognized as a fundamental regulator of gene expression. To understand how regulatory T cells acquire and maintain their identity, we need to investigate not only which molecular players are present, but also how they are arranged in space.

Expansion microscopy is uniquely suited to address this challenge because it enables nanoscale imaging while preserving the native spatial organization of the cell. By physically expanding the specimen, it allows us to visualize and quantitatively analyze subnuclear structures that would otherwise remain below the diffraction limit.

Combined with high-resolution quantitative imaging, this approach allows us to map the spatial organization of chromatin, nuclear compartments, and lineage-defining transcription factors directly in primary regulatory T cells.

Rather than replacing transcriptomic or epigenomic approaches, expansion microscopy complements them by adding a spatial dimension that sequencing alone cannot provide. Ultimately, this integrated strategy will allow us to determine whether distinct nuclear architectures contribute to regulatory T-cell specialization, stability, and function.

Could you walk us through your experience accessing France-BioImaging?

The collaboration started long before the first images were acquired. Together with Samira, we discussed the biological hypothesis, selected the most appropriate nuclear markers, optimized sample preparation, and designed the imaging workflow best suited to answer our biological question.

I still remember seeing the first successfully expanded regulatory T-cell nucleus appear on the screen. It was not yet a biological discovery, but it was the first tangible demonstration that a question we had previously been unable to address had become experimentally accessible. For the first time, we could begin to explore the internal nuclear landscape of these rare primary immune cells at a scale that had previously been beyond our reach.

For me, this illustrates one of the greatest strengths of France-BioImaging. It is not simply a network providing access to sophisticated microscopes: it is a network of scientists who help transform an ambitious biological question into a robust imaging strategy.

As an immunologist, working closely with imaging experts has been extremely enriching. This interdisciplinary dialogue has broadened the way I think about my research and opened new perspectives at the interface between immunology, quantitative imaging, and spatial biology.

How did this access contribute to advancing your project? Which results did you obtain?

The project is still ongoing, but the impact of France-BioImaging is already tangible.

Beyond providing access to technologies unavailable at our institute, the collaboration has enabled us to establish a robust multiscale imaging pipeline specifically adapted to primary regulatory T cells. Together with the IBENS team, we optimized sample preparation, expansion protocols, image acquisition, and quantitative image analysis.

We are now generating the first datasets that will allow us to quantitatively compare the nuclear organization of different regulatory T-cell populations.

Most importantly, this access has transformed what was initially a conceptual hypothesis into a biologically testable question, and has established a technological framework that will support many future projects in our laboratory.

What are the next steps or future perspectives for your research project?

Our immediate objective is to determine whether distinct nuclear architectures are associated with different regulatory T-cell states. Beyond describing nuclear organization, we aim to identify structural features that distinguish specialized Treg populations.

A particularly exciting question is whether nuclear architecture merely reflects cellular state or actively contributes to maintaining the regulatory lineage. We hypothesize that specific features of three-dimensional genome organization provide a structural framework supporting the transcriptional and epigenetic networks underlying Treg stability.

To address this, we will generate multidimensional spatial maps of the Treg nucleus by combining chromatin organization with the spatial distribution of lineage-defining transcription factors and histone modifications. Integrating this nuclear spatial imaging approach with transcriptomic, DNA methylation, and functional analyses will reveal how nuclear organization contributes to Treg stability and function.

More broadly, we envision nuclear architecture as a new dimension of immune-cell characterization, complementing molecular biomarkers and providing innovative ways to assess Treg stability.

Ultimately, this work demonstrates how advanced imaging can bridge structural cell biology and immunology by bringing spatial biology to the nuclear level, opening new perspectives for precision immunology.

What advice would you give to researchers who are considering applying for the France-BioImaging User Access Support?

I would strongly encourage researchers to apply. France-BioImaging offers much more than outstanding imaging technologies: it gives you access to an exceptional community of imaging scientists, and it fosters genuine scientific collaborations.

My advice: start with a clear biological question, not with a specific technology. The facility scientists are true scientific partners who can help refine the experimental design, identify the most appropriate imaging approaches, and develop robust quantitative workflows.

For me, the greatest strength of France-BioImaging is precisely this combination of technological excellence, scientific expertise, and collaborative spirit. It enables researchers to tackle ambitious biological questions that would be difficult to address within a single laboratory.

If I had the opportunity to apply again, I would do it without hesitation.

Like Meryem, you can benefit from France-BioImaging User Access Support to access cutting-edge imaging technologies available across the infrastructure!