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RNA as a drug target


CEITEC

About the Project

RNA is an attractive drug target with enormous potential for future treatment of systemic and cancer-related pathologies. Yet, most of the currently applied and developed small molecule therapeutics for cancer and systemic diseases target proteins. Interestingly, from 20000 human protein-coding genes (1.5% of the human genome) only 2000-3000 genes are considered to be disease-related. In this context, small molecule drug therapies target less than 700 genes which represents less than 0.05% of the genome. While the portion of protein-coding information in the genome is minor, the ENCODE consortium has proposed that more than 75% of our genome is transcribed into RNAs. This also includes large non-coding regions of mRNAs, namely 3’UTRs which contain many regulatory elements important for spatio-temporal regulation of gene expression, such as translational control, RNA transport and localization and mRNA decay. We propose to target non-coding mRNA elements with small molecules to alter gene expression. We will focus on cancer-related genes, where protein targets often lack druggable elements and therefore targeting them on the mRNA level is an attractive alternative. Our research aims to identify functional mRNA motifs that can bind small molecules and to reveal common small molecule scaffolds which interact with similar 3D RNA structures and thus form a basis for rational lead optimization.

We are looking for highly motivated PhD candidates with background in biochemistry and biophysics who share our fascination for RNAs regulating gene expression.

Keywords: targeting non-coding mRNA, gene expression, neurodegenerative diseases, cancer, mRNA motifs, cryo EM, NMR spectroscopy

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. Nagel et al, EMBO Reports, 2016, 17, 1516.
2. Di Giorgio et al, Med. Chem. Commun., 2019, 10, 1424.



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