Topic: ribosome profiling

This 36-month salaried PhD in Mar Albà’s group investigates which recently evolved microproteins have biological functions. The researcher will integrate ribosome profiling, phylostratigraphy and population genetic data from gnomAD and UK Biobank to predict evolutionary constraint. Candidate functions will be tested through CRISPR-Cas9 screens in cancer cell lines, assessing growth, drug resistance and DNA repair. Validated models and datasets will contribute to the ORFeome platform. The project includes collaboration with Simon Elsässer’s group, doctoral enrolment at Universitat Pompeu Fabra

Silencing of FMR1 and loss of its gene product, FMRP, results in fragile X syndrome (FXS). FMRP binds brain mRNAs and inhibits polypeptide elongation. Using ribosome profiling of the hippocampus, we find that ribosome footprint levels in Fmr1-deficient tissue mostly reflect changes in RNA abundance. Profiling over a time course of ribosome runoff in wild-type tissue reveals a wide range of ribosome translocation rates; on many mRNAs, the ribosomes are stalled. Sucrose gradient ultracentrifugation of hippocampal slices after ribosome runoff reveals that FMRP co-sediments with stalled ribosomes,