Dissecting the molecular events that control cell fate decision-making in budding yeast

This 4-year PhD studentship is offered in Dr Folkert van Werven’s Cell Fate and Gene Regulation Group based at the Cancer Research UK London Research Institute (LRI). The successful applicant will join the Crick PhD Programme in September 2015.

The aim of the research group is to elucidate the molecular mechanisms by which the cell integrates multiple signals to achieve a binary cell fate decision – whether or not to differentiate. Unfolding these mechanisms is critical for the understanding of how cell specialization leads to multicellularity during development, and how impaired signaling can cause abnormal development and diseases such as cancer. The budding yeast S. cerevisiae is an ideal model system to study this problem. In response to a combination of extracellular and intracellular cues budding yeast undergoes a highly conserved cell differentiation program called gametogenesis. Since entry into gametogenesis is controlled by only two master regulators in this model organism, there is unique opportunity to study the molecular and quantitative aspects of this cell fate [1].
The promoter of the master transcription factor for entry into gametogenesis, IME1, integrates nutrient and mating-type signals to make the binary cell fate decision [1]. To understand how these signals are integrated, it is essential to identify all the molecular players and pathways involved in acting at the IME1 promoter. Recently, we showed that in haploid cells IME1 is repressed by the lncRNA IRT1 [2]. Induction of IRT1 recruits the methyltransferases Set1 and Set2 to methylate histone H3 at lysine 4 and 36. These marks are recognized by the histone deacetylase complexes Set3C and Rpd3(S) and establish a repressive chromatin state in the IME1 promoter [2]. The mechanism of cell fate control described here provides a starting point for further investigations. The student joining this research group will receive extensive training and access to a broad range of molecular/biochemical/genetic techniques. Research projects could involve the following:
(1) Investigate how widespread gene regulation by lncRNAs is across the genome;
(2) Investigate how multiple lncRNAs control cell fate;
(3) Screen for novel factors required for gene repression by lncRNAs;
(4) Investigate how nutrient signaling controls cell fate;
The above are just examples of the sort of projects that might be available in this research group. One studentship is available and the precise project will be decided upon in consultation with the supervisor.

Talented and motivated students passionate about doing research are invited to apply for this PhD position. Students who join the 2015 Crick PhD Programme, will start their PhDs at the LRI in September 2015, will register for their PhD at one of the Crick partner universities (Imperial College London, King's College London or University College London), and will transfer into the Crick with their research group in early 2016.

Applicants should hold or expect to gain a first/upper second-class honours degree or equivalent in a relevant subject and have appropriate research experience as part of, or outside of, a university degree course and/or a Masters degree in a relevant subject.
APPLICATIONS MUST BE MADE ONLINE VIA OUR WEBSITE BY 5PM GMT NOVEMBER 12TH 2014. APPLICATIONS WILL NOT BE ACCEPTED IN ANY OTHER FORMAT.
http://www.london-research-institute.org.uk/phd/