Martinez-Arias Lab
Department of Genetics, University of Cambridge
Fernando Faunes
Postdoc
f.faunes@gen.cam.ac.ukDepartment of Genetics,
Downing Street, Cambridge
CB2 3EH,England
Telephone: +44 1223 766595
Fax: +44 1223 333992
The mechanisms underlying the maintenance of pluripotency in Embryonic Stem (ES) cells are incompletely understood (Silva & Smith, 2008). My main interest is to understand the molecular basis of the pluripotency and cell differentiation.
The activity of a small network of transcription factors centred on Nanog, Sox2 and Oct4 are essential for the maintenance of the pluripotency. Dynamic heterogeneities in gene expression are a characteristic of ES cell cultures and might regulate their properties.
In particular, the levels of Nanog -a readout of the pluripotent state- have been shown to fluctuate between a high and a low expression states (Kalmar et al, 2009). The distribution and its dynamics are correctly simulated by an excitable system driven by transcriptional noise (Kalmar et al, 2009; Arias & Hayward, 2006).
Our hypothesis is that the molecular basis for these heterogeneities is transcriptional noise associated with Nanog expression. Our aim is to test this by measuring Nanog expression directly, with single cell resolution in real time in large populations (Chubb et al, 2006; Eldar & Elowitz,2010).
Specifically, my work will include:
- To develop a method for detecting transcription from the nanog promoter in single ES cells in real time;
- To analyze the transcription levels of nanog in single ES cells in real time;
- To determine the effects of signalling pathways on the dynamics of nanog expression.
This work should provide insights into the mechanisms involved in the maintenance of the pluripotency and their regulation by transcriptional noise.
References
- Silva J, Smith A. Capturing pluripotency. Cell 2008, 132(4):532-536.
- Kalmar T, Lim C, Hayward P, Munoz-Descalzo S, Nichols J, Garcia-Ojalvo J, Martinez Arias A. Regulated fluctuations in nanog expression mediate cell fate decisions in embryonic stem cells. PLoS biology 2009, 7(7):e1000149.
- Chubb JR, Trcek T, Shenoy SM, Singer RH. Transcriptional pulsing of a developmental gene. Curr Biol 2006, 16(10):1018-1025.
- Arias AM, Hayward P. Filtering transcriptional noise during development: concepts and mechanisms. Nature reviews 2006, 7(1):34-44.
- Eldar A, Elowitz MB. Functional roles for noise in genetic circuits. Nature 2010, 467(7312):167-173.