MRC National Institute for Medical Research, London
Science for Health
Reverse engineering the network: Identifying maternal components of gene regulation in early vertebrate development
Project supervisor: Mike Gilchrist (Systems Biology)
The Gilchrist lab is trying to understand the gene regulatory networks that control early vertebrate development, using Xenopus as a model system. We have preliminary data on gene activation before, during and shortly after the mid-blastula transition (MBT), enabling us to construct a catalogue of gene activation events in the early embryo. We understand how to go about finding the downstream targets of the transcription factors activated at this point, but it is not obvious how to find the trans-activating factors for those genes transcriptionally activated at MBT. This will require us to reverse engineer the network.
The project will focus on a small number of developmentally critical genes and proceed in phases: (i) determine a test set of six transcription factors of interest from our gene activation catalogue; (ii) understand the landscape of likely promoter and enhancer regions in the vicinity of these genes from the extensive histone modification ChIP-seq data available from the Veenstra group; experimental determination of active enhancers through (iii) exploration of the possibilities of using customized TAL Effectors proteins as enhancer/promoter blockers, or alternatively (iv) more traditional promoter analysis techniques; (v) use DNA affinity capture assay and mass spec. to determine transcription factors bound to the active enhancer regions, and finally (vi) validate the candidate upstream factors by knockdown and RNA-seq analysis.
Deliverables
- Functionally important enhancers for target gene set.
- List of verified activating transcription factors for target set.
- Protocol for application of method to the larger set of MBT-activated genes.
FUNDING AND NOTES
- Generously funded with stipend and mobility allowance to support placements in partner laboratories.
- A multidisciplinary, cross-cultural and competitive training programme in developmental and computational biology research.
- Secondments and a targeted training programme
Eligibility:
- Applicants should have a Masters degree or completed Honours program in the field of molecular-, developmental-, or computational biology which would formally entitle them to embark on a doctorate. Candidates with a background in computer science and relevant expertise (modelling of gene regulation, machine learning) can also apply.
- Applicants should be in the first 4 years (full-time equivalent) of their research careers, starting at the date of obtaining the degree.
- The applicants must not have resided or carried out their activity (work, studies, etc) in theUnited Kingdom for more than 12 months in the 3 years immediately prior to his/her recruitment.
- Applicants can have a non-European nationality.
- Applicants preferably are familiar with computational biology, bioinformatics and statistics as well as with molecular biology and embryonic development.
- The applicants should be proficient in written and spoken English with a minimum standard ELTS score of 6.5, or equivalent.
To apply: Please download and complete the application form from the downloads section on the right-hand side. On receipt of your application your two referees will be contacted. Your application may not be considered until your references are in place.
The deadline for applications is: June 07, 2013
Downloads
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