Temporal and spatial aspects of the genetic regulatory network underlying mesoderm and neural tube formation

The aim of this project is to use ChIP-seq approaches to study the genetic regulatory network (GRN) that is initiated by T box gene family members and which results in the formation of mesoderm and the repression of neural tissue in the vertebrate embryo. To understand how T box proteins function in different regions of the embryo, the INTACT method of Henikof and the BiTS-Chip approach pioneered by Furlong will be adapted for both zebrafish and Xenopus embryos, in addition to developing an approach in which chromatin is tagged in particular cells of the embryo via expression of GFP-tagged histones (FHiP-ChIP). This work will help understand how T-box proteins regulate mesoderm formation and neural differentiation in space and time.
To test the GRN that is defined through these experiments it will be necessary to inhibit gene function. Although antisense morpholino oligonucleotides have proved valuable for this purpose, it is difficult to assess their efficacy and they are hard to control. Smith has therefore optimized the TALENs approach for Xenopus, and this will allow him to create mutant animals to allow much better definition of gene function. He is also exploring the use of TALOR approaches to inhibit the functions of particular enhancer regions in the developing embryo.

Deliverables
1. Development of INTACT, BiTS-ChIP, FHiP-ChIP in Xenopus and zebrafish embryos, and ES cells.
2. Appropriate transgenic lines.
3. Regionalized embryo ChIP data.
4. Mutant Xenopus strains using TALENs technology.

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.

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