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Integrative structural biology of 3’UTRs / RNA as a drug target


Project Description

The non-coding part of the genome vastly increased from worm to humans while the number of protein-coding genes remained constant. This expansion includes 3’UTRs of mRNAs with an average length of 1.2 kb in humans and functions in mRNA transport, translational control and mRNA decay. Despite the importance of 3’UTRs for spatial and temporal control of gene expression, the molecular basis of 3’UTR functions is largely unknown. We will determine complexes of 3’UTR signals with Staufen1 protein and the ribosome which regulate mRNA stability and control translation. Using integrative structural biology approaches, including NMR spectroscopy and cryo-EM, we will unravel the molecular basis of Staufen-mediated 3’UTR functions in posttranscriptional regulation of gene expression and thus provide new insights into how deregulation can lead to diseases such as cancer and neurodegeneration. We are looking for highly motivated PhD candidates with background in biochemistry and biophysics who share our fascination for RNA-protein interactions regulating gene expression.

Keywords: Three Prime Untranslated Region, 3’UTR, mRNPs, RNA-protein networks, Staufen, RNA-based pulldown, gene expression, 3’UTR mutations, cryo EM, NMR spectroscopy, targeting non-coding mRNA, neurodegenerative diseases, cancer, mRNA motifs

HOW TO APPLY: Register for this call using the registration form at http://ls-phd.ceitec.cz/http-ls-phd-ceitec-cz/ and submit required documents to receive support with the preparation of the application and all formalities. Your application package will be forwarded to the supervisor for preliminary revision.
Applicants who wish to pursue a degree at the CEITEC PhD program must hold the equivalent of a Master’s degree (MSc) in a similar field (four- or five-year undergraduate degree). The application can be submitted before obtaining the Master’s degree; however, the applicant should obtain a degree within five months after the application deadline.

Funding Notes

Admission for studies, student registration for the full-time study program, and proper fulfillment of student duties constitute the student’s right to a regular income of 22 000 CZK (850 EUR). Information is available at View Website

Living costs and other practicalities available at View Website

References

1. Sugimoto et al, Nature 2015, 519:491-4.
2. Yadav & Lukavsky, Prog. Nucl. Magn. Reson. Spectrosc. 2016, 97:57-81.
3. Gleghorn & Maquat, Trends Biochem. Sci. 2014, 39:328-40.
4. Nagel et al, EMBO Reports, 2016, 17, 1516.
5. Di Giorgio et al, Med. Chem. Commun., 2019, 10, 1424.

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