Liang-Cui, Niki and Hugh, together with many honour and MSc students, spent the last three years building a powerful pipeline for identifying RNA-binding residues in putative RNA-binding proteins.
In collaboration with Prof. Atlanta Cook, Prof, David Dockrell and Dr. Douglas Houston, we recently were awarded a 5 year Medical Research Council Programme grant to continue our research on Helix-Turn-Helix proteins and their association with RNA in Staphylococcus aureus.
We are currently looking for two talented post-docs wishing to join our team in 2024!
Our Wellcome Trust iCM PhD student Sofia Esteban Serna attended the 2022 Brittish Yeast meeting.
She presented her work on what we believe is a new mechanism for co-transcriptionally regulating noise in gene expression during stress responses.
From the Microbiology Society Website:
"British Yeast Group 2022: From Genomes to Cells took place on 7–9 September 2022 and was held at the University College London, UK.
Our S. aureus (MRSA) RNA interactome papers (2x!) have been published in Nature Communications!!!
Using CLASH we unearthed large RNA-RNA interaction networks in this pathogenic and antibiotic resistant bacterium.
Together with Jai Tree's group we identified interactions between non-coding RNAs and mRNAs that regulate (1) tolerance of vancomycin, our last-line antibiotic for battling MRSA, and (2) the production of cytolytic toxins that enable MRSA to survive and even thrive in the hostile host environment.
Using two very different but highly complementary high-throughput approaches we unearthed the RNA-binding proteome in two clinically-relevant Staphylococcus aureus strains.
We show that our data is highly enriched for metabolic enzymes, in particular those with Rossmann folds.
Moreover, we find that many HTH domain transcription factors also bind RNA, suggesting that they also play a global role in post-transcriptional regulation.
We demonstrate that the CcpA transcription factor also uses HTH domain sequences to bind dsRNA with comparable affinities.
Our paper describing novel algorithms for the detection of RNA structural changes in high-throughput sequencing data has been accepted by Genome Biology!
This project was in close collaboration with Guido Sanguinetti's group and the analyses were performed by two students that at the time were undergraduate students doing internships!
A fantastic result!
The FEBS Journal asked us to write a review early last year and Niki (my PhD student) spent several months doing literature research during the lockdown.
The abstract of the review is below.
Sofia Esteban Serna joins our lab!
Sofia is a new Wellcome Trust iCM PhD student in our lab and her project involves understanding the role of RNA-binding proteins in tight regulation of gene expression.
When some genes are expressed at too high levels it can be toxic to the cell. We found a mechanisn that involves RNA-binding proteins that suppresses this overshooting and keeps tight control of expression of some stress-responsive genes.
Sofia's goal will be to dissect this mechanism and understand how it contributes to stress adaptation.
My former PhD student Ira Iosub spent about four years working on a project to identify Hfq-mediated sRNA-target interactions.
Her reasearch has unearthed a plethora of novel sRNA-mRNA interactions as well as many sRNA-sRNA interactions that potentiall connect many different metabolic pathways.
Consistent with recent work from Hannah Margalit's lab, we found that sRNA-mRNA interactions that are reproducibly detected are more likely to impact steady state levels of their mRNA targets.
This work was done in collaboration with the labs of Jai Tree and Gabriella Viero!
Our JoVe paper describing a detailed protocol for kinetic CRAC (chiCRAC) has been accepted by JoVe!
The work describing the mammalian iCLIP experiments were done by Ross Cordiner who is a post-doc in Torben Heick Jensen's lab.