organisation - the Instituto Gulbenkian de Ciência

IMMUNE
REGULATION
Carlos E. Tadokoro Research Fellow
PhD in Immunology, University of São Paulo, 2001
Post-doctoral fellow, New York University, USA
Research Fellow at the IGC since 2010
link to external website
The ultimate function of the immune system is to cooperate with other body
systems in order to maintain homeostasis within multi-cellular organisms.
To perform such a task, cells and molecules of the immune system evolved to
distinguish between “self” and “non-self” molecules. We are interested in better
understanding the regulation that occurs inside the immune system, focusing
our attention on a particular cell type called regulatory T cell. We combine
classical cellular analyses with intra-vital imaging techniques to investigate the
function of immune cells in tissues under various conditions of activation/inflammation.
To this aim, we develop surgical procedures and tools to perform
these analyses using two-photon microscopy, which allow the observation of
single-cell dynamics and cell interactions as well as their spatial localization
inside the organs.
GROUP MEMBERS
Márcia M. Medeiros (Post-doc, started at November)
Henrique B. Da Silva (Visiting Ph.D. Student (collaborator))
Susana Caetano (Research Technician, started in September)
COLLABORATORS
Juan J. Lafaille (New York University, USA)
Michael L. Dustin (New York University, USA)
Cláudio R. F. Marinho (University of São Paulo, Brazil)
Maria Regina D'Império Lima (University of São Paulo, Brazil)
Ana Cláudia Zenclussen (Otto-von-Guerricke University, Germany)
FUNDING
Fundação para a Ciência e a Tecnologia (FCT), Portugal
GENERATION OF NEW TRANSGENIC ANIMALS
FOR in vivo TRACKING OF REGULATORY T CELLS
The main objective of this project is to develop new tools to acquire information
about in vivo tracking of a specific type of cell inside the immune system
called Regulatory T Cells (Tregs). We will develop tools to allow the in vivo
cell fate mapping of Tregs inside organs and also throughout the rest of the
mouse body. We will develop new intra-vital microsurgeries, use “two-photon”
microscopy, and generate new genetically engineered animals to track any cell
of interest. The major challenge is no longer the microscopes used, but in the
development of intra-vital microsurgeries that allow the exposure of internal
organs with minimal or no trauma. Therefore, this project has a strong core in
Research and Development (R&D). To visualise these cells we will generate new
genetically manipulated mouse lines expressing a photo-activated GFP (paGFP)
under specific promoters and conditional transgenic mouse lines based on
“Tet ON-OFF” systems.
We developed intra-vital imaging techniques, in use by IGC groups (intra-vital
imaging of placenta, used by the Disease genetics group) or international collaborators;
submitted two papers: Zenclussen, A. C., et al, Clin. Invest; Silva, H.
B., et al, Eur. J. Immunol.); and published two papers: Olivieri, D., et al, J. Integr.
Bioinform., 2011 Sep 8(3):180).
A
B
In vivo PICTURE OF PLACENTA BLOOD FLOW.
A - Maternal blood in red and foetal blood in green, with arrow showing the region
of chorionic plate. B - Higher magnification of placenta, showing details of chorionic
plate and labyrinth zone.
3D reconstruction of uterus, showing DC distribution (green), during oestrus phase
of oestrus cycle.
IGC ANNUAL REPORT ‘11
RESEARCH FELLOWS
81