Date : 03/02/2011

Laboratory
Integrative biology of human dendritic cells and T cells
Inserm U932 - Institut Curie
26 rue d'Ulm 75005 Paris
Director : Vassili Soumelis

PhD Supervisor
Vassili Soumelis
email : This e-mail address is being protected from spam bots, you need JavaScript enabled to view it
phone : +33 1 44 32 42 27

Subjects
1.: Systems biology
2.: Immunology
3.: Cell biology

Tools-Methodologies:
1.: Cellular immunology
2.: Computational biology
3.: Mathematical modeling

Summary of lab's interests

Our lab is interested on the factors determining the behavior of innate and adaptive immune cells, mostly dendritic cells and T cells. We exclusively work in the human system. We aim at recreating physiological and pathological environments in order to understand their influence on cellular state and behavior at the large-scale level. We try to consider as much as possible the complexity of tissue microenvironments and the integration of multiple stimuli/signals by immune cells, rather than focusing on individual stimuli. We developed a strong interface between immunology and bioinformatics/computational biology.The questions we ask have impact in the fields of immunology and systems biology, as well as on our understanding of the physiopathology of human diseases.

Summary of project

Living systems are open systems that change state and behavior in relation to their environment. Conversely, their state impacts on the way they respond to given environmental stimuli. For example, an individual may be stressed in a noisy environment. However, the degree of stress will also depend on the state of the individual. If he is himself relaxed and well, he will be less sensitive to a stressful environment. Hence, the state of a living system is highly intricated with its environment. This concept applies to any living system independent of its order: organisms, organs, tissues, and cells. However, the parameters determining the complex interactions between the state and the environment of a system are not well understood. In our laboratory, we use the immune system as a model to study the reciprocal interaction between cell state and its environment. Immune cells exist in a large diversity of states and subsets, which evolve in variable environments related to the nature of the danger/aggression of an organism. This makes it a very interesting and appropriate model. Our work is mostly performed on human primary cells, in order to closely mimic the in vivo situation and the physiopathological situations. Immune cells are cultured in different environments. Cell state is evaluated at the large scale by its transcriptional profiling, combined to medium throughput phosphoproteomics. Computational biology and modeling methods are used in order to describe and explain the complex interactions between environment and cell state in a quantitative and multiparametric manner. Specific questions are: 1) which are the effects of single stimuli on cell state; 2) which are the effects of multiple stimuli on cell state? How are multiple stimuli integrated by a given cell?; 3) How are these effects integrated over time (dynamic modeling)?; 4) How cell state impacts the response of a cell to a given stimulus? Because of the general nature of the questions we ask, we expect impact not only for our understanding of the immune system, but also on our view of living systems and their interaction with their environment. We hope to uncover novel mechanisms and rules governing the plasticity and diversity of living systems.

Interdisciplinarity of the project

The interdisciplinarity of the project can be viewed at two levels: 1) Conceptual level: concepts of systems biology, cell biology, and immunology are important for a global view and understanding of the project. However, it is not required that the candidate masters all these fields. The work environment of our Institute and interdisciplinarity of the team is an important aspect enabling this project. 2) Methodological level: methods related to immunology, cell and molecular biology, as well as computational biology and mathematical modeling are required. Again, the interdisciplinarity of the team is a critical aspect. We expect from the candidate to master at least one of these fields, and to work in collaboration with team members in order to find the most appropriate solutions to each question. The candidate should also be open-minded and willing to improve his own interdisciplinary skills, in order to be more independent and to understand the language of other disciplines. Because of this strong interdisciplinarity, we believe the project is best suited for FdV, in order to identify particularly open minded students that focus on solving a broad and important conceptual question outside the frame of a given discipline. For example, sociology, psychology, human and animal behavior could also enrich the conceptual thinking around our central question of interaction between the state and the environment of a living system.