Interview with the leaders of the priority area 4 “Health and disease at the extremes of life”

In the lead-up to the Town Hall meeting due to take place on June 30, the senior management team and the Department of Communications and Public Affairs wanted to take this opportunity to introduce you to the scientists responsible for scientific priorities identified in the Strategic Plan, so you can find out more about their roles, the challenges entailed by their priority areas, key projects, and also upcoming events. 

 

Interview with the leaders of the scientific priority “Health and disease at extremes of life”:

Ana Cumano
Head of the Hematopoietic Development group

Darragh Duffy,
Head of the Translational Immunology unit

Philippe Sansonetti,
Emeritus Professor at the Institut Pasteur and the Collège de France

Chiara Zurzolo
Head of the Membrane Traffic and Pathogenesis unit

 

► Can you tell us about the scientific priority that has been assigned to you as part of the Pasteur 2030 Strategic Plan?

Ana Cumano: I have been entrusted with co-leading the scientific priority on “Health & disease at the extremes of life,” with a focus on the early life - particularly centered in immunology and development.

I am an immunologist at the intersection with Development and Stem Cell Biology and I am interested in understanding how the immune system is established. The hematopoietic system is established through independent but overlapping generations of hematopoietic progenitors with different properties. The thymus is an essential organ in the production and education of T lymphocytes. Signals delivered from lymphoid cells to thymic epithelial medullary cells induce the expression of peptides representative of all tissues in the body that are involved in the negative selection of autoreactive T cells. Our laboratory has been interested in understanding how the first lymphoid cells impact the thymus architecture and function and how persistent these effects are in adult life. Interfering with the initial stages of thymic maturation might impact immunity for life such that infection, stress, metabolic disorders and others, early in life, could have an impact in the adult immune system. 

Evidence in the mouse indicates that the hematopoietic cells that produce the first lymphoid progenitors correspond to an intermediate generation of multipotent cells that do not contribute to the adult hematopoietic stem cell compartment, in other words, that lymphocytes early in life are different in origin from those found in the adult. This could in turn have implications in managing pediatric disease and vaccination early in life. To highlight these differences is the observation that childhood leukemia is a unique disease. The translocations found in childhood lymphocytic leukemias are shared in twins that have the same placenta arguing that embryonic lymphoid cells unlike their adult counterparts are a preferential target for these translocations.

Most evidence for the different properties of perinatal versus adult lymphoid cells comes from the mouse models and very limited information is available in humans. It would be therefore essential to gather information on the properties of the infant human system. In this line the initiatives of Darragh are particularly relevant with connection to human immunology, with Philippe with vaccines, child-mother relations and in the interface with clinicians and Chiara in how early life injury or inflammation impact the adult nervous system and ageing.

Philippe Sansonetti: As part of the Pasteur 2030 strategic plan, I have been tasked with coordinating the scientific program dedicated to Maternal and Child Health. This program is part of priority area 4, “Health & disease at the extremes of life,” which explores how early life events influence long-term health trajectories, vulnerability to age-related diseases, and differences in susceptibility between the sexes. 
When we talk about Mother and Child Health, we are not excluding the role of the father, but rather focusing on what is now called “the first 1,000 days of life,” - from fertilization to the age of two. This period is crucial, as it corresponds to intense developmental activity in the embryo, placenta, and fetus, and later, postpartum, in the infant, where major functions continue to mature, particularly psychomotor, hematopoietic, immune, digestive, and metabolic systems.

This time window represents a period of heightened sensitivity to environmental influences, both beneficial and harmful. All of these influences, whether indirect during pregnancy or direct after birth are collectively referred to as the “exposome,”. These exposures can impact fundamental developmental processes at every stage. By “fundamental process,” we mean the complex developmental, genetic, and molecular machinery shaped by evolution, which, in the ante- and postnatal mother-child cocoon, guides the construction of a new individual; one who is  particularity vulnerable during this time..
In summary, our objective is to stimulate fundamental research on these critical stages, using a cross-disciplinary and integrative approach.

Chiara Zurzolo: I have been entrusted with co-leading the scientific priority on “Health and disease at the extremes of life,” with a focus on the late-life end of the spectrum - particularly aging and neurodegenerative diseases. These pathologies, such as Alzheimer’s and Parkinson’s, are escalating globally with increased life expectancy, yet they remain poorly understood and largely incurable.

As cell biologist, my specific objective is to understand how aging affects cellular communication, organelle function, and immune responses in the brain and other systems. In this context, we are particularly interested in how misfolded proteins, mitochondrial dysfunction, and inflammatory signals interact across cell types- factors that are at the root of many late-onset diseases. However, addition to neurodegenerative disorders like Alzheimer’s and Parkinson’s, aging is a major risk factor for a broad spectrum of chronic diseases, including cardiovascular disease, certain cancers, type 2 diabetes, and age-associated immune decline (immunosenescence). These conditions that often intersect and share common molecular hallmarks such as inflammation, mitochondrial stress, and impaired cellular repair mechanisms, often co-occur and interact in complex ways, making it critical to understand aging not just at the level of individual organs, but as a systemic biological process.

This is not simply about characterizing pathologies, but about deciphering the fundamental cellular and molecular mechanisms that make the aging brain - and aging body - more vulnerable to disease.

Darragh Duffy: I have been entrusted with co-leading the scientific priority on “Health and disease at the extremes of life,” with a specific focus on the different effects of biological sex and gender throughout life. 

As an immunologist my research focuses on understanding why immune responses are different between two individuals, and what are the clinical consequences of those differences. For the first objective, this is mostly addressed through the Milieu Interieur consortium, a LabEx funded project which I co-coordinate with Lluis Quintana-Murci and involves over 20 Institut Pasteur teams along with teams from 8 other institutes. From the consortium’s work we have really appreciated how age strongly impacts immune responses during adulthood, with those differences likely even more important at the extremes of life. We, along with many others in the field, have also realized the importance of biological sex on immune variability, and given the strong sex disparities seen in many diseases this offers a major opportunity for clinically impactful research. For example, women have much greater susceptibility to autoimmune diseases, while men experience higher mortality from severe infections and are more likely to develop certain types of cancer. Both biological sex; which is associated with sex chromosomes and hormones, and gender; a more fluid category that is socially constructed, can impact disease risk and occurrence in different ways and need to be considered in parallel.  In the past Western medicine has mostly overlooked clinical differences due to sex and gender, but there is increasing awareness of the need to address these limitations. 

Therefore, given the overall objective of scientific priority 4 to focus on health and disease during early development (lead by Ana), the mother-child dyad (lead by Philippe), and the end stages of life (lead by Chiara) there is both a need and opportunity to consider the impact of sex and gender throughout these different stages of life.

► How does the Institut Pasteur stand out?

The Institut Pasteur offers a unique advantage for addressing the biology of aging and juvenile immune system: a critical mass of researchers across disciplines, all within walking distance. This proximity enables constant scientific dialogue - between immunologists, vaccinologists, neuroscientists, developmental and stem cell biologists, cell biologists, microbiologists as well as epidemiologists and clinical researchers. The strength of Institut Pasteur is the diversity.

The Institut Pasteur offers also huge potential for addressing questions of how biological sex impacts health and disease. For the moment there are not so many teams with this focus but there is potential on the campus. 

Moreover, we have access to cutting-edge technologies - including live imaging, high-resolution fluorescence and electron microscopy, high-resolution flow cytometry, numerous mutant mouse lines, zebra fish models, advanced cell models such as induced pluripotent stem cells (iPSC)-derived cells, and various organoid systems (from gut to brain) that replicate the complexity of human organs in vitro. 

In addition, the standardized immunomonitoring, novel pre-clinical animal models, vaccination cohorts and collaborative patient cohorts provides ample opportunity for new discoveries in these areas. 

Concerning the program mother and child, this cannot go along without working with other institutions/partners.

We have a lot of progress to do connecting with some other institutions, developing some more specific approaches, especially the medical one. We are trying to offer the best we must collaborate and build some very original and productive interfaces. Nevertheless, we have already identified several specific areas of research:

-    Study of the role of the maternal microbiome on embryonic development, then of the infant microbiome during the postnatal period on immunity, neurological development, and metabolism;
-    Analysis of the effects of dysbiosis (maternal or infantile) on motor, immune, and cognitive functions;
-    Evaluation of the impact of nutrition and inflammation control during pregnancy and postpartum;
-    Research on lactation as a central vector of biological and immune transmission.

► How is your work organized?

As leaders of this scientific priority, we are currently building on our complementary expertise -spanning immunology, cell biology, developmental biology, neuroscience, and infection biology - to foster interdisciplinary collaborations around core questions: How does early life disease impact adult immunity (immune response versus autoimmunity)? How may this differ between females and males?

We join interests within the priority area 4 in exploring how early-life events, including developmental and environmental factors, shape long-term health trajectories and influence susceptibility to age-related diseases like obesity, diabetes, Alzheimer’s disease, etc.

Also, through the Pasteur Network there is a unique opportunity to address these questions in diverse populations around the world, work that has already begun at the University of Hong Kong-Pasteur Research Pole and the Institut Pasteur de Dakar through the Healthy Human Global Project inspired by Milieu Intérieur LabEx.

We have also collaborations with university hospital federations, the Institut Robert-Debré du Cerveau de l'Enfant (University Hospital Institute), the mother-child unit at the Port Royal maternity hospital, Imagine Institute, Karolinska Institute for pediatric immunology and Trinity College Dublin for immune aging for instance.
Since the launch of the scientific priority “Health and disease at extreme ages of life,” we begun to organize meetings with various scientists on campus to better understand their projects, expertise, needs, and potential synergies, particularly at the medical-scientific interface. One particularly constructive meeting was held in May with the Institut Pasteur in Italy (Fondazione Cenci-Bolognetti), organized through the International Affairs Department of the Institut Pasteur, focused on the theme of aging and inflammaging.

At the same time, we organize regular meetings with the coordinators of other cross-disciplinary programs (in particular priority areas 3 and 4) to strengthen synergies.

We recently launched an internal survey to identify people interested in scientific priority 4 in order to create subgroups.  A few participants have already completed the survey on mother-child dyad. Additional surveys will soon be released for the other topics. Following this, we will work closely with the Philanthropy team to develop a clear, public-facing narrative that highlights both the social and scientific urgency of addressing age-related diseases. This narrative will support the creation of flagship interdisciplinary programs focused on the immunology of infancy, late-life immunity in humans, neurodegeneration, and inflammaging.

Moreover, we will organize new seminars that will be held under different angles, with the participation of doctors who conduct high-quality research in hospitals, as well as conclaves on programming disease, bringing together about 20 people for two days. We will also organize collective meetings once a year with all the interested people who will present their work and, consequently, their collaboration.  

We will also host joint symposia, promote early-career collaboration through Seed Grants, and generate white papers to identify future directions. Particularly important is working closely with the communications to diffuse the initiatives through the campus.

We already have four events scheduled: 
-    a one-day congress on October 23rd on sex differences in immunity with a European working group focused on this topic, 
-    a Translational Science Day on integrative biology of the mammary gland and lactation organized on November 20 with the Medical Department
-    a Translational Science Day on the theme of “Organoids: From Stem Cells to Disease Modeling” in January 2026 with the Medical Department
-    a workshop on disease programming for early 2026, in coordination with Gérard Eberl (priority area 3).

Finally, we will also launch a monthly newsletter to keep the network dynamic.

► Will you be involved in cross-cutting projects? If so, which ones?

Late life diseases don’t happen in isolation - they are the outcome of lifelong exposures, infections, genetic predisposition, and environmental factors. That makes our work naturally aligned with priorities like Gérard Eberl’s focus on disease origins in priority area 3.
For example, we are investigating how early-life infections, or chronic inflammation might predispose individuals to neurodevelopmental diseases early in life or neurodegenerative and/or autoimmune disorders late in life. We are also exploring how the biology of the beginning and end of life might be more interconnected than previously understood.
Our coordinating role is not to direct researchers, but to facilitate the emergence of ideas and collaborations. It is about creating an environment conducive to innovation, ensuring that everyone has the intellectual freedom essential to high-quality research.

►What is your goal for 2030 as head of scientific priority? What results do you intend to achieve?

By 2030, our goal is to understand the impact of the maternal and infant microbiome on embryonic development and postnatal immunity. We will investigate the role of lactation and perinatal nutrition in biological and immune transmission.

Our aim is also to position the Institut Pasteur as a leading player in understanding the molecular and cellular mechanisms of aging, particularly with regard to brain and immune system health and resilience. Current research clearly indicates that an individual’s biological age is determined by the age of the brain and the immune system.

This includes:
-    Establishing flagship interdisciplinary programs on immunology of the infant, late life immunity in humans, neurodegeneration and inflammaging.
-    Attracting and supporting scientists who bridge immunology, metabolism, neuroscience, developmental biology and cell biology
-    Strengthening international partnerships to study aging in diverse populations
-    Developing educational programs to train the next generation of researchers in cross-disciplinary aging science and infant immunity
-    Building a clear, public-facing narrative that emphasizes the social and scientific urgency of addressing the relationship between infant and age-related diseases
-    Ensure the systematic recording and analysis of sex in all biological studies and gender in all human studies conducted by Institut Pasteur researchers and collaborators
-    Identify funding and create an environment conducive to investment, including philanthropy

 

 

Photo : Guillaume Ombreux