Diversity and plasticity of Th cell types predicted from regulatory network modelling

Denis Thieffry (Faculté des Sciences de Luminy (Aix-Marseille), département de biologie computationnelle, TAGC.)

Alternative cell differentiation pathways are believed to arise from the concerted
action of signalling pathways and transcriptional regulatory networks. However, the
prediction of mammalian cell differentiation from the knowledge of the presence of
specific signals and transcriptional factors is still a daunting challenge. In this respect,
the vertebrate hematopoietic system, with its many branching differentiation
pathways and cell types, is a compelling case study. In this paper, we propose an
integrated, comprehensive model of the regulatory network and signalling pathways
controlling Th cell differentiation. Our main aim is to gain insight into the potential
heterogeneity and plasticity of late Th cell lineages. As the majority of available data
are qualitative, we rely on a logical formalism to perform extensive dynamical
analyses. To cope with the size and complexity of the resulting network, we use an
original model reduction approach coupled to a stable state identification algorithm.
To assess the effects of heterogeneous environments on Th cell differentiation, we
have performed a systematic, extensive series of simulations, considering various
prototypic environments. Consequently, we have identified stable states
corresponding to canonical Th1, Th2, Th17 and Treg subtypes, but these were found
to coexist with other transient hybrid cell types that co-express combinations of Th1,
Th2, Treg and Th17 markers in an environment-dependent fashion. In the process,
our logical analysis highlights the nature of these cell types and their relationships
with canonical Th subtypes. Finally, our logical model can be used to explore novel
differentiation pathways in silico.

Simple micro-tools to study complex cell behaviors : from yeast morphogenesis to dendritic cell migration and orientation of the mitotic spindle in mammalian cells

Mathieu Piel (Institut Curie, Unité Compartimentation et dynamique cellulaires, Equipe Biologie cellulaire systémique de la polarité et de la division)

Fine control of the micro-environment of single cells is a major improvement for in
vitro cell biology studies. But it is important that device fabrication remains the easy
part of the experiment, to be compatible with sophisticated biological assays. In the
last years, while studying cell polarity, we developed and used simple tools ­ mainly
cell adhesive micro-patterns and micro-channels in the micron range - that turned out
to be crucial for answering fundamental cell biology questions. I will first rapidly
present a few examples illustrating our recent work, showing how simple micro-
fabricated tools enable new questions to be asked in vitro, but also make cell biology
more quantitative and open the way to new quantitative cell based assays for
complex cell functions. These will include: how fission yeast cells can maintain a rod
like shape through growth and division? How can budding yeast cells maintain a
private conversation with a single mating partner when surrounded by a crowd of
suitors? What is the effect of cell adhesive geometry on cell polarity and cell division
axis?
I will then spend some time on a new research program in which our team is
involved, whose aim is to understand how leukocytes and invasive cancer cells
migrate in confined environments.

Modeling biological systems: bridging the gap between formalisms and biological contexts.

Damien Eveillard (Université de Nantes, Computational Biology group, LINA - UMR CNRS 6241)

Modeling biological systems is a difficult task. By nature, these systems are complex
and partially known. Several recent formalisms tackle this problem by focusing on
distinct biological features that occur in dynamical living systems. Whereas some
focus on qualitative biological behaviors, others analyze times between the events of
interest or quantify them. This talk proposes an overview of the modeling techniques
at disposal, with a particular emphasis on the conditions of their use, as well as their
respective limitations. In particular, we propose to highlight the "user" aspect of
modeling systems from different biological fields: from molecular biology to ecology.