Date : 05/02/2011

Internship proposal for : Master 2

Laboratory
Integrative biology of human dendritic cells and T cells
Inserm U932
Institut Curie
26 rue d'Ulm 75005 PARIS
Director : Vassili Soumelis
Lab's website
Main discipline : Systems Biology

Supervisor
Vassili Soumelis
email : Cet e-mail est protégé contre les robots collecteurs de mails, votre navigateur doit accepter le Javascript pour le voir
phone : +33 1 44 32 42 27

Subjects

1.: Systems biology
2.: immunology
3.: Cell biology

Tools and methodologies

1.: Cellular immunology
2.: Computational biology
3.: Mathematical modeling

Summary of lab's interests

Our lab is asking how human innate and adaptive immune cell types integrate various signals from normal and pathological microenvironments. We are particularly interested in the influence of the environment on the state and behavior of a cell, as well as the influence of the cell state on its response to a given environmental stimulus. We use the immune system as a model to ask these broad questions related to environmental plasticity, the generation of living systems diversity, and their implications in health and disease.

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.