PhD topic in Structural Biology of Gene Regulation Research Group

Updated: 4 months ago
Job Type: PartTime
Deadline: 18 Feb 2024

6 Jan 2024
Job Information
Organisation/Company

CEITEC, Masaryk University
Research Field

Biological sciences » Biology
Biological sciences » Other
Chemistry » Biochemistry
Researcher Profile

First Stage Researcher (R1)
Country

Czech Republic
Application Deadline

18 Feb 2024 - 23:00 (UTC)
Type of Contract

Temporary
Job Status

Part-time
Offer Starting Date

1 Sep 2024
Is the job funded through the EU Research Framework Programme?

Not funded by an EU programme
Is the Job related to staff position within a Research Infrastructure?

No

Offer Description
Research group homepage:

https://stefl-lab.ceitec.cz/


Topic title: Deciphering the Argonaute Loading Mechanisms in RNA-Silencing Pathways

Supervisor: prof. Mgr. Richard Štefl, Ph.D.

Annotation:

This PhD theme focuses on unraveling the intricate process of Argonaute protein loading by small RNAs, a critical step in gene regulation within RNA-silencing pathways, which are pivotal in both healthy and diseased states of animals and plants. Despite over two decades of research into the microRNA pathway and RNA interference, the precise mechanisms of miRNA strand selection and transfer to Argonaute proteins remain elusive. We propose the existence of two distinct mammalian Argonaute loading pathways, orchestrated by Dicer and heat shock protein chaperones, which both involve charged intrinsically disordered regions that have been overlooked in previous structural studies. The PhD project aims to dissect these mechanisms using electron cryomicroscopy (cryoEM). The objective is to elucidate the structures of critical complexes involving heat shock protein chaperone/co-chaperone-Argonaute-RNA and Dicer-Argonaute-RNA assemblies. By integrating cryoEM with functional analyses, the project aspires to establish the mechanistic principles of Argonaute loading. The findings of this PhD project will be instrumental in advancing RNA-based therapeutic applications and understanding one of the most crucial regulatory cellular processes.

Keywords: gene silencing, small RNA, Argonaute, cryoEM, structures

Recommended literature:

  • Dicer structure and function: conserved and evolving features. Zapletal D, Kubicek, K, Svoboda P, Stefl R EMBO Reports (2023) 24:e57215 doi:10.15252/embr.202357215
  • microRNAs in action: biogenesis, function and regulation. Shang R, Lee S, Senavirathne G, Lai EC. Nat Rev Genet. 2023 doi:10.1038/s41576-023-00611-y.
  • Requirements on candidates:

    Biochemistry/molecular biology

    APPLY: https://ls-phd.ceitec.cz/how-to-aplly/

     


    Requirements
    Additional Information
    Work Location(s)
    Number of offers available
    1
    Company/Institute
    CEITEC, Masaryk University
    Country
    Czech Republic
    Geofield


    Where to apply
    Website

    https://ls-phd.ceitec.cz/how-to-aplly/

    STATUS: EXPIRED

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