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Transcriptional responses to cellular stress

  • Full or part time
  • Application Deadline
    Applications accepted all year round
  • Competition Funded PhD Project (Students Worldwide)
    Competition Funded PhD Project (Students Worldwide)

Project Description

Position for a PhD student is available in the group of Dr Pawel Grzechnik at the University of Birmingham. The aim of the project is to understand how eukaryotic cells remodel RNA biology in order to survive stress generated by pathological conditions and external stressors.

Project outline
Exposure to acute stress like extreme temperatures, accumulation of reactive oxygen species or high salt concentration reduces cell viability or fitness and therefore immediate adaption is crucial for cell survival. Such rapid change of cell physiology requires coordinate and precise alternation of gene expression. One of the most dramatic transformations happens at the transcriptional level. Transcription of large number of genes is shut down while stress responders are activated and robustly transcribed. Synthesized stress-induced mRNA are not subjected to quality control [1] and are exported to cytoplasm via specific, promoter-dependent mechanisms [2]. Such unusual mRNA biology of stress induced genes enables cells to immediately tailor protein production and allows them to survive extreme conditions.
In eukaryotic cells mRNA 3’ end processing, which involves endonucleolytic cleavage followed by the addition of the poly(A) tail, is one of the most important steps in gene expression regulation [3]. For example, the 3’ end maturation complex responds to cellular stimuli and decides about the nuclear and cytoplasmic fate of mRNA through the generation of distinct 3’ end termini. Furthermore, a poly(A) tail protects mRNA from degradation and promotes translation. The function of the cleavage and polyadenylation machinery extends far beyond simple maturation of mRNA ends.
Recent studies reveal that cellular stress such as osmotic shock, viral infections or carcinogenesis can all affect mRNA 3’ end formation [4-6]. Thus, the goal of this project is to employ a wide range of high-throughput and classic RNA analysis to investigate how the mRNA 3’ processing regulates expression of stress-induced genes and contributes to the cellular stress response in a model organism Saccharomyces cerevisiae and human cells.

The project will employ a wide variety of classic and modern biochemical and cell biology techniques including molecular cloning, genome editing (CRISP-Cas9), RNA-seq, transcriptional analyses (e.g. ChIP-seq), cell sorting and growth and survival assays.

Host environment:
University of Birmingham is a world-leading University ranked in the top 100 out of over 8,000 universities in the world. The Grzechnik lab is interested in different aspects of nuclear RNA biology with a special focus on transcriptional processes in eukaryotic cells and provide an exceptional environment for personal and scientific development.

Person specification
We are looking for a highly motivated, driven and enthusiastic person interested in RNA biology. Applicants should have a strong background in molecular biology and hold or expect to obtain at First Class Degree (1:1) or equivalent in genetics/molecular biology/medicine or relevant field.

Funding:
The School of Biosciences offers a number of UK Research Council (e.g. BBSRC, NERC) PhD studentships each year. Fully funded research council studentships are normally only available to UK nationals (or EU nationals resident in the UK) but part-funded studentships may be available to EU applicants resident outside of the UK. The deadline for applications for research council studentships is typically at the end of January each year.
Each year we also have a number of fully funded Darwin Trust Scholarships. These are provided by the Darwin Trust of Edinburgh and are for non-UK students wishing to undertake a PhD in the general area of Molecular Microbiology. The deadline for this scheme is also typically at the end of January each year.

Informal enquiries about the post should be directed to Dr Pawel Grzechnik (.)

Grzechnik lab website :https://www.grzechniklab.com

Funding Notes

All applicants should indicate in their applications how they intend to fund their studies. We have a thriving community of international PhD students and encourage applications at any time from students able to find their own funding or who wish to apply for their own funding (e.g. Commonwealth Scholarship, Islamic Development Bank).
The deadline for applications for fully funded research council studentships is typically at the beginning of January each year.

References

1. Zander, G., et al., mRNA quality control is bypassed for immediate export of stress-responsive transcripts. Nature, 2016.
2. Zid, B.M. and E.K. O'Shea, Promoter sequences direct cytoplasmic localization and translation of mRNAs during starvation in yeast. Nature, 2014. 514(7520): p. 117-21.
3. Proudfoot, N.J., Transcriptional termination in mammals: Stopping the RNA polymerase II juggernaut. Science, 2016. 352(6291): p. aad9926.
4. Vilborg, A., et al., Widespread Inducible Transcription Downstream of Human Genes. Mol Cell, 2015. 59(3): p. 449-61.
5. Rutkowski, A.J., et al., Widespread disruption of host transcription termination in HSV-1 infection. Nat Commun, 2015. 6: p. 7126.
6. Grosso, A.R., et al., Pervasive transcription read-through promotes aberrant expression of oncogenes and RNA chimeras in renal carcinoma. Elife, 2015. 4.

How good is research at University of Birmingham in Biological Sciences?

FTE Category A staff submitted: 42.80

Research output data provided by the Research Excellence Framework (REF)

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