Share
Deciphering the Argonaute Loading Mechanisms in RNA-Silencing Pathways
Doctoral study program
Life Sciences (Faculty of Science, Masaryk University)
Supervisor
Annotation
Every cell must decide which genes to turn on and which to silence. One of the most powerful systems controlling this process is guided by small RNAs—tiny molecular instructions that direct Argonaute proteins to specific target genes. Together, they form the core of RNA silencing, a fundamental pathway that shapes development, protects cells from harmful genetic elements, and maintains cellular health.
Despite its importance—and despite discoveries that led to two Nobel Prizes—we still do not understand a central question: how does an Argonaute protein acquire its RNA guide and become programmed to recognize specific targets?
This PhD project will tackle this long-standing mystery using state-of-the-art electron cryomicroscopy (cryo-EM), a revolutionary technology that allows us to visualize biological machines at atomic resolution. The student will investigate how Argonaute proteins are activated and loaded with their guide RNAs by two distinct cellular pathways involving the proteins Dicer and HSP90.
By determining high-resolution structures of key molecular assemblies and combining them with biochemical and functional experiments, the student will reveal how RNA guides are selected and loaded into Argonaute proteins. These studies will capture molecular machines in action and uncover fundamental principles governing gene regulation in animals.
The project sits at the interface of structural biology, RNA biology, and biophysics, offering training in cutting-edge cryo-EM methods, protein biochemistry, and molecular mechanism discovery. Beyond advancing our understanding of gene regulation, the work may provide insights into human developmental disorders linked to Argonaute dysfunction and inform future RNA- and peptide-based therapeutic strategies.
Join us to solve one of the most fundamental unanswered questions in RNA biology.
Recommended literature
- Dicer structure and function: conserved and evolving features. Zapletal D, Kubicek, K, Svoboda P, Stefl R EMBO Reports (2023). 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
Research area
RNA/nucleic acids research in health
Keywords
RNA biology; structural biology; Argonaute loading; Cryo-electron microscopy (cryo-EM); RNA silencing mechanisms; Intrinsically disordered regions (IDRs)
Funding of the PhD candidate
GACR, OP JAK
Requirements for candidate
Biochemistry/molecular biology/strucktural biology
Information about the supervisor
Prof. Richard Stefl is a leading structural biologist whose lab combines cryo-EM, NMR, and integrative structural biology to uncover how RNA–protein complexes control gene expression and cellular regulation. As an ERC grant holder and head of the CEITEC Centre for Structural Biology, he offers PhD students access to cutting-edge technologies, interdisciplinary mentoring, and an inspiring environment at the forefront of RNA biology and molecular mechanisms of gene silencing.
Overall Summary Output
- Total publications: 49
- Total citations: 2,400+
- H-index: 28
- Journal highlights: Cell, Molecular Cell, Genes & Dev, EMBO J, PNAS, NSMB, Nature Comms
- Supervision since PI (total): 8 postdocs, 1 technician, 13 PhD students, 11 undergraduate students.