Download Master Project Proposal Title: Enhancing reprogramming and

Master Project Proposal
Title: Enhancing reprogramming and stemness through long non-coding RNAs.
Synopsis: Revolutionary progress has been achieved recently following the discovery that
adult somatic cells can be reprogrammed (named induced pluripotent stem cells – iPSC) by
expressing a combination of 4 transcription factors (Oct4, Sox2, Klf4 and cMyc; 4-TFs). This
discovery holds immense promise for clinical applications, as it implies that pluripotent cells
can, in principle, be produced from the patient’s own cells. Recently, Dr. Manuel Serrano
(CNIO, Spain) and others showed that cells from elderly individuals reprogram less efficiently
than equivalent cells from young individuals. This could be explained by the accumulation of
specific marks with the aging process. Examples are the accumulation of short telomeres,
higher levels of tumor suppressors or epigenetic alterations that accumulate during aging.
The main objective of this proposal is to unravel, correct and comprehend age related
molecular barriers envisaging an efficient reprogramming of somatic cells. In particular, our
research proposal focuses on the impact of RNA-mediated gene regulation on stemness and
somatic cell reprogramming. RNA is an ideal molecule to regulate biological networks, since
it encodes sequence information and possess a great structural plasticity. From the plethora
of ncRNAs, the function of the long non-coding RNAs (lncRNAs) remain elusive. lncRNAs are
by definition >200bp in length that lack significant protein coding capacity. lncRNAs have a
key regulatory role across diverse biological pathways modulating cell fate decisions.
Preliminary results indicate that modulation of lncRNAs could guide the early steps of
reprogramming or cellular commitment, being initial players which could prime the cells to
cell-fate decisions. The current proposal encloses several novel and state-of-the-art
strategies to attain the aspiration of define the role of lncRNAs in cell decision programs.
This proposal envisage the characterization of novel lncRNAs signatures of mESC undergoing
differentiation since this should provide candidates that will be screened for their capacity to
modulate reprogramming and regulate pluripotency. We believe this approach constitutes a
novel strategy to study the impact of lncRNAs in the reprogramming of aged cells and we
anticipate that the output of this proposal will generate important contributions to the aging
research. Ultimately, our results will contribute for improving the regeneration of tissues
from older individuals, thus creating novel opportunities for the prevention and treatment
of age-associated diseases.
Supervisor: Bruno Bernardes de Jesus, MCFonseca Unit, [email protected]
Co-Supervisor (if applicable): Maria Carmo-Fonseca, [email protected]
Bibliography (facultative):
#1 - doi:10.1073/pnas.1004584107
#2 - doi:10.1038/nature10398
#3 - doi:10.1073/pnas.1212769110
#4 - doi:10.1038/nature12586
#5 - doi:10.1016/j.cell.2007.11.019
#6 – doi:10.1101/gad.455708
Remunerated or volunteer training: Volunteer
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