This sandwich placement will be based in the lab of Folkert van Werven.
Project background and description
Cell differentiation programs depend on dynamic and global changes in gene expression to ensure proper morphologic changes. How regulation of gene expression is controlled during cell fate transitions is often not well understood. For this project we use budding yeast because it is a well traceable genetic model and yeast cells can differentiate synchronously into four haploid spores in a process also known as sporulation or gametogenesis. This differentiation program is set in motion by a master regulator transcription factor and a highly conserved RNA methyltransferase protein complex. m6A is a highly abundant mRNA modification but the function of the mark is not well understood.
The aim of the project is to gain insight into molecular function of m6A methylated mRNAs. A genetic approach will be taken to investigate how m6A affects gene expression. The goal of the project is two-fold: (1) Dissect how m6A machinery controls gene expression including the roles of mRNA decay and translation [1]; (2) Delineate where and how m6A gets deposited in the cell [2].
Since m6A mRNA methylation is highly conserved from yeast to humans, it is our hope that the results from this project will give insights into how this mark regulates gene expression across species, thereby enabling further delineation of the clinical significance of m6A.
Candidate Background
The post holder should embody and demonstrate the Crick ethos and ways of working: bold, open and collegial. The candidate must be registered at a UK Higher Education Institution, studying in the UK and must have completed a minimum of two years’ undergraduate study in a relevant discipline, and on track to receive a final degree grade of 2:1 or 1. In addition, they should be able demonstrate the following experience and key competencies:
- This project is open to candidates with various backgrounds. Most important is that the candidate has strong curiosity in basic science.
- Good knowledge in relevant scientific area(s)
- Good written and spoken communication skills
- Ability to work independently and also capable of interacting within a group
References
1. Varier, R.A., Sideri, T., Capitanchik, C., Manova, Z., Calvani, E., Rossi, A., . . . van Werven, F.J. (2022)
N6-methyladenosine (m6A) reader Pho92 is recruited co-transcriptionally and couples translation to mRNA decay to promote meiotic fitness in yeast.
eLife 11: e84034. PubMed abstract
2. Ensinck, I., Maman, A., Albihlal, W.S., Lassandro, M., Salzano, G., Sideri, T., . . . van Werven, F.J. (2023)
The yeast RNA methylation complex consists of conserved yet reconfigured components with m6A-dependent and independent roles.
eLife 12: RP87860. PubMed abstract
