(April 2023) Our manuscript on oncogenic RAS regulation of ribosome biogenesis via nucelolin is finally out in EMBO Journal!
After nearly a year of hard work and addressing all the reviewers comments, our manuscript on RAS regulation of ribosome biogenesis through an ERK-CK2-nucleolin axis is finally out in EMBO Journal! Big congratulations to our recent PhD graduate Syahmi who initiated this project, Emilie who carried it over the finish line, and all other present and past Mardakheh team members (Martin, Fede, Maria, and Alina) who contributed to the work! Also, big thanks to Jernej Ule and Rupert Faraway, our amazing collaborators!
(March 2023) Congratulations to Elliott for successfully defending his PhD!
A big well done to Elliott for successfully defending his PhD on 24th of March! He becomes the second PhD student graduating from Mardakheh lab! Also many thanks to the fantastic viva examiners Prof. Marco Gerlinger (BCI) and Dr. Paul Huang (ICR) for conducting the viva! It was a pleasure to have you here and Elliott really enjoyed the experience!
Congratulations Dr Whittaker! I hope you enjoy all the special presents (and please don't finish them quickly :D)!
(March 2023) CRUK funded MBPhD project available in Mardakheh lab!
Are you a third year MBBS student at the Barts and the London School of Medicine and Dentistry? Are you interested in cancer research? Then look no more! As part of the CRUK City of London Centre (https://www.colcc.ac.uk/), we are offering an exciting MBPhD project (September 2023 start date) on understanding and exploiting the impact of Nucleophosmin1 (NPM1) mutations on modulation of ribosome synthesis in Acute Myeloid Leukaemia (AML).
NPM1 is an RNA-binding protein that plays a key role in organisation of the nucleoli, the subcellular sites of ribosome biogenesis. NPM1 mutations are found in >30% of all adult AML cases, and result in mislocalisation of the protein to the cytoplasm. However, the exact molecular impact of NPM1 mislocalisation on AML development is still unclear. This project aims to decipher the consequences of NPM1 mislocalisation on the nucleolus of AML cells, assessing how ribosome biogenesis is specifically modulated, and how such modulation may be therapeutically exploited in treatment of AML.
For more information on the project and how to apply, check out this page:
2023 MBPhD project Mardakheh – CRUK – City Of London Cancer Centre (colcc.ac.uk)
Massive congratulations to our technician Martin, who won the BCI technician of the year award. Martin not only has been a vital pillar of our lab, but also a tremendous help to others beyond our group. In the past year, Martin has enabled several proteomics collaborations with other BCI labs, trained many newcomers in our centre, and greatly helped with setting up our Institutes' brand new RNA suite. Martin has also been smashing it with his contributions to our labs papers and grants, as well as being an key contributor to an upcoming patent application from our team.
Thanks to all these amazing achievements, Martin received this award on the 27th of January from the BCI director, Professor Nick Lemoine (Pictured), during the BCI Burns night/New Year celebration Party, which was held at the iconic St Barts Great Hall.
Well done Martin! This one is so well deserved!
BIG Congratulations to Federica for delivering an excellent talk on her PhD work at the South Coast RNA Network Meeting, and winning the best PhD student talk prize! This years meeting was held at the University of Portsmouth, where Federica presented her new data on how LARP6 can recognise diverse functional groups RNAs inside the cell, as well as important insights on how these binding events may be regulating different pro-tumourigenic functions in mesenchymal cancers. Well done Fede!
Our latest work describing how oncogenic RAS signaling modulates the RNA-bound proteome, is now out on bioRxiv: https://doi.org/10.1101/2021.12.16.472890
In this manuscript, we systematically profile changes in the RNA-bound proteome downstream of RAS oncogene, and discover a novel mechanism of ribosome biogenesis upregulation downstream of oncogenic RAS signalling, that is mediated via regulating the RNA-binding activity of Nucleolin (NCL).
A big well done to Syahmi who spearheaded this project, as well as Martin, Federica, Maria, and our MSc student Wanling, all of whom contributed to this study. Also big thanks goes to our fantastic collaborators, Rupert and Jernej for
their
critical support with regards to our NCL iCLIP analysis.
Are you interested in uncovering a novel mechanism of post-transcriptional dysregulation during cancer progression? We have a post-doctoral position available in our lab, so get in touch if you are curious!
Over the summer, we said goodbye to the first postdoc of Mardakheh's lab, the amazing Maria Dermit. Maria moved to the biotech sector to do some really cool science with stem cells at bit.bio. Even though we are very happy for you Maria, We will be really missing you (yes even your extremely messy bench!). We wish you all the best. Wherever you go to in your future endeavours, one thing for sure is that you will be achieving amazing things!
Adiós dama de T-Rex!
Interested in performing quantitative proteomics analysis of cell-protrusions like we did in our recent publication (Dermit et al., 2020)? If so, we have a detailed protocol for you, now published in STAR Protocols: https://doi.org/10.1016/j.xpro.2021.100462
Credit goes to Maria for preparing this extremely well-written and detailed protocol, which even has videos of the experiments shot on a body cam! Also check out her Github entry for all the data analysis pipelines you
need: https://demar01.github.io/protrusionproteome/index.html
We have a fully funded CRUK PhD position available for the start of September 2021. Get in touch if you are interested in doing a PhD on RBPs and their role in pancreatic cancer. More details on the position, and how to apply can be found here:
https://www.bartscancer.london/about/vacancies/cancer-research-uk-phd-studentships/
Our manuscript in Developmental Cell (Dermit et al., 2020) was chosen as the paper of the month by the Barts Cancer Institute's executive board. A very big well done to Maria and the team for their achievment!
(November 2020) Our paper on LARP6 regulation of ribosome biogenesis by RNA localisation is out!
Almost 10 months after the initial submission, our paper on regulation of ribosome biogenesis by subcellular mRNA localisation is finally out in Developmental Cell! We are very proud of Maria for her great effort in completing the revisions despite huge challenges caused by the pandemic (e.g. 4 months of lockdown!). Many thanks to all the team members and collaborators who contributed to the work. We are also grateful to our funders MRC and Barts Charity for their generous support.
You can read the open-access paper here:
https://www.cell.com/developmental-cell/fulltext/S1534-5807(20)30796-6#%20
There is a wealth of multiomics data in the paper, including subcellular mRNA and protein distributions between protrusions and cell-bodies of 6 different human cell-lines. If you fancy exploring this data more, checking for instance how your mRNA or protein of interest is distributed between protrusions and cell-bodies in these cell-lines, you can also use this dashboard within our resource page:
(September 2020) Best poster prize for Syahmi!
Congratulations to Syahmi for winning the best poster prize at the Barts Cancer Institute's annual PhD day 2020. In his poster, Syahmi presented his findings on the importance of ribosome biogenesis for pancreatic Ductal Adenoarcinoma (PDAC) development, showing that addiction to mutant KRAS in PDAC depends on the KRAS ability to enhance ribosome biogenesis.
(July 2020) Back to the lab.
Roughly 3 ½ months passed since any of us lifted a pipette. But now the time has come to bring those old skills to the test. Even so only a few of us can be at the bench at once, we are doing our best to make up for the time lost. Continuing with where we left off, as well as working on new ideas which we have accumulated over the lock down.
(June 2020) Maria delivers a fantastic talk at BCI Thursday seminar series
Maria told us (remotely) about her recent work on LARP6 and regulation of ribosome biogenesis in migrating cells at BCI Thursday seminar series. Watch her full talk here (QMUL access only):
https://bcinet.qmcr.qmul.ac.uk/thursday-seminar-series-webinar-archive/
(December 2019) An update of our preprint is now available on bioRxiv
Check out the revised version of our preprint, now out on bioRxiv: https://www.biorxiv.org/content/10.1101/829739v2
(November 2019) Our lab's first ever preprint is now out on bioRxiv
Work spearheaded by our amazing postdoc, Maria Dermit, describes a novel mechanism by which mesenchymal-like migrating cells upregulate ribosomal protein synthesis and ribosome biogenesis, through RNA localization. Check out the manuscript here: https://www.biorxiv.org/content/10.1101/829739v1
(July 2019) Faraz presents at FASEB/EMBO RNA Localization and Local Translation Conference
Faraz and Maria attended this years' FASEB/EMBO RNA Localization and Local Translation conference in Snowmass, Colorado, where Faraz spoke about our soon to be published story on how spatial organisation of ribosomal protein mRNAs plays a crucial role in regulating ribosome biogenesis in migratory mesenchymal-like cells, and how this pathway is hijacked by highly aggressive cancer cells to enhance malignant growth and invasion.