MRC National Institute for Medical Research, London
Science for Health
Towards a model of transcriptional regulation in early vertebrate embryos
Project supervisor: Mike Gilchrist (Systems Biology)
This project aims to build a computational model of gene regulation in the early vertebrate embryo, with a particular focus on temporal regulation and the downstream targets of transcription factors (TFs) which are activated at the start of the maternal-zygotic transition. The very early Xenopus embryo is a relatively simple system with small numbers of cells and molecular players, and therefore an ideal system to model the transcriptional dynamics in the cascade of events that leads to the onset of gastrulation. This work will build on data already generated in the lab (high resolution time-based expression profiles).
The work will use a thermodynamic modelling approach to identify likely binding events in the regulatory regions of genes activated downstream of MBT-activated TFs. Protein concentrations and dissociation constants will be measured using band shifts assays and a quantitative assessment will be made of the accumulation of TFs over time between activation of the primary transcription factors and activation of their targets. We will determine or refine position weight matrices of motifs bound by the TFs and determine the role of both high affinity and low affinity sites in the modulation of transcription rates.
Deliverables
- Initial set of key genes and assemblage of existing data and initial framework for model.
- Acquisition of input data (protein concentrations, dissociation constants, PSSMs, and kinetic data).
- Computational model framework for identifying likely direct targets 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 the United 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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