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Master Project Proposal
Title:
Control of mucosal innate immunity by circadian cues
Synopsis:
Circadian rhythms, long-known for their crucial roles in mammalian physiology and
behaviour, are emerging as important regulators of the immune system. Immune
parameters present daily oscillations and disruption of circadian rhythms has been
associated with inflammatory pathologies. However, how the circadian clock impacts
on immune cell fate and function remains utterly unexplored.
Innate lymphoid cells (ILC) are a recently described family of effectors with key roles
in tissue homeostasis, maintenance of epithelial barrier function and mucosal
defence. ILC lineage commitment and function have been perceived as being
programmed. However, we recent demonstrated that ILCs are also controlled by
environmental signals.
We hypothesize that ILCs are under the control of the circadian clock in anticipation
to environmental changes. Supporting this hypothesis several transcription factors
crucial for ILC lineage specification can coordinate inputs from the circadian clock.
Thus, we propose to combine genetic, cellular and molecular approaches to decipher
the role of the circadian clock on ILC ontogeny and function.
Understanding how environmental cues integrated by the circadian clock regulate
ILCs will be important to unravel ILC function and will pave the way for new
therapeutic targets in cancer and inflammatory diseases that are major Public Health
concerns.
Supervisor:
Henrique Veiga-Fernandes ([email protected])
Bibliography from the group:
Veldhoen, M and Veiga-Fernandes, H (2015). Feeding immunity: skepticism,
delicacies and delights. Nature Immunol. 16:215-219.
Xu, W., Domingues, R.G., Fonseca-Pereira, D., Ferreira, M., Ribeiro, H., Lopez-Lastra,
S., Motomura, Y., Moreira-Santos, L., Bihl, F., Braud, V., Kee, B., Brady, H., Coles,
M.C., Vosshenrich, C., Kubo, M., Di Santo, J.P. and Veiga-Fernandes, H. (2015). NFIL3
Instituto de Medicina Molecular-Email: [email protected] - www.imm.fm.ul.pt – NIF-506134466
Av.Prof.Egas Moniz-Edifício Egas Moniz- 1649-028 LISBOA – Tel. 217999411 – Fax 217999412
orchestrates the emergence of common helper innate lymphoid cell precursors. Cell
Reports 10:2043-54.
Fonseca-Pereira, D., Arroz-Madeira, S., Rodrigues-Campos, M., Barbosa, I.,
Domingues, R.G., Bento, T., Almeida, A.R.M., Ribeiro, H., Potocnik, A., Enomoto, H.
and Veiga-Fernandes, H. (2014). The neurotrophic factor receptor RET drives
haematopoietic stem cell survival and function. Nature 514:98-101.
van de Pavert, S. A., M. Ferreira, R. G. Domingues, H. Ribeiro, R. Molenaar, L.
Moreira-Santos, F. F. Almeida, S. Ibiza, I. Barbosa, G. Goverse, C. Labao-Almeida, C.
Godinho-Silva, T. Konijn, D. Schooneman, T. O'Toole, M. R. Mizee, Y. Habani, E. Haak,
F. R. Santori, D. R. Littman, S. Schulte-Merker, E. Dzierzak, J. P. Simas, R. E. Mebius,
and Veiga-Fernandes, H. (2014). Maternal retinoids control type 3 innate lymphoid
cells and set the offspring immunity. Nature 508:123-127.
Remunerated or volunteer training:
To be defined according to the candidate’s experience.
Instituto de Medicina Molecular-Email: [email protected] - www.imm.fm.ul.pt – NIF-506134466
Av.Prof.Egas Moniz-Edifício Egas Moniz- 1649-028 LISBOA – Tel. 217999411 – Fax 217999412