Postdoctoral position in Cancer Metabolism

Our colleague Bruno Galy offers a postdoc position in the field of ‘Cancer Metabolism’ to work at the ‘Virus-associated carcinogenesis’ division in the DKFZ, Heidelberg, Germany.


One major interest of the Galy lab is iron metabolism. Iron is a trace element important for a plethora of cellular functions and like other metabolic pathways, iron homeostatic mechanisms are frequently altered in cancer. Using a combination of biochemical and molecular biology assays together with state-­‐of-­‐the-­‐art mouse models and organoid cultures, the candidate will study the function of central regulatory systems of iron homeostasis in various aspects of tumorigenesis, with a strong focus on hepatic and intestinal cancer. The successful applicant will more specifically investigate the impact of local iron mismanagement in cancerous cells versus cells of the tumor microenvironment on the inflammatory processes that lead to carcinoma formation.


To inquire about the position, the job profile, and the conditions, contact Dr. Bruno Galy.

A brave new world of RNA-binding proteins

Our last review was recently published in Nature Reviews – Molecular and Cell Biology. We discuss about the recurrent identification of unorthodox RBPs by proteome-wide methods to identify proteins bound to RNA, and discuss about the potential biological meaning of this exciting discovery.


What can we expect from the discovery of so many new RBPs? Some might side with Miranda from Shakespeare’s The Tempest and marvel at these novel and goodly RBPs that populate the RNA interactome. Others might think of Huxley’s brave new world and fear dystopia, considering the newly discovered RBPs as nonconformist misfits lacking biological function. Which roles do these new RBPs play?


A brave new world of RNA-binding proteins.

Hentze MW, Castello A, Schwarzl T, Preiss T.
2018 Jan 17. doi: 10.1038/nrm.2017.130.

 

PhD position in Barcelona

Our friend, Mayka Sanchez is applying for a PhD position within the framework of an MSCA-COFUND, funded by the EU and co’funded by La Caixa. The program is called INPhINIT and the deadline for application in 2nd February 2018.

  • 3-year contract in a stimulating environment
  • Complementary training
  • Secondments at national and international organisations (Universities, Research Center and Private sector)
  • Mentor appointed by ”la Caixa” Foundation from its network of alumni, the ”la Caixa” Fellows’ Association
  • Involvement in communication and dissemination activitie

Requisites
Candidates applying for a fellowship of the programme will be evaluated accordingly to their CV, letters of reference and interview.

  • Candidates must have obtained a Master degree in the last 4 years
  • A good command of English  (B2 level required)
  • It is also mandatory not to have resided in Spain more than 12 months in the last 3 years before 29 May 2018.

Application here

The activity of TRIM25 is controlled by RNA

The E3 ubiquitin ligase TRIM25 is an antiviral factor recently discovered to bind RNA by the RNA interactome studies (Castello et al., 2012 and Kwon et al., 2013). In a recent work led by our collaborator Gracjan Michlewsky (Wellcome Centre for Cell Biology, University of Edinburgh), we dissected how this protein binds to RNA and what are the consequences of this interaction in TRIM25 function. We discovered that TRIM25 binds RNA via its PRY/SPRY domain and that the interaction with RNA enhances TRIM25 E3 ligase activity, which is necessary for its antiviral role. Using CLIP analyses we showed that TRIM25 binds G-rich sequences present in hundreds of cellular RNAs. Moreover, We discovered that TRIM25 controls the levels of a key component in the interferon response pathway, ZAP (also known as PARP13 and ZC3HAV1).


In conclusion, the E3 ligase activity of TRIM25 is controlled by RNA, breaking once more the view that proteins act on RNA and not the opposite.


Original publication:
RNA-binding activity of TRIM25 is mediated by its PRY/SPRY domain and is required for ubiquitination
Nila Roy Choudhury, Gregory Heikel, Maryia Trubitsyna, Peter Kubik, Jakub S. Nowak, Shaun Webb, Sander Granneman, Christos Spanos, Juri Rappsilber, Alfredo Castello and Gracjan Michlewski
BMC biology

Decapping host and viral RNAs

In a recent work with Yolanda Revilla’s lab (CBMSO, Madrid) published in the Journal of Virology, we investigated the role in RNA metabolism of a protein from a complex DNA virus, called African swine fever virus (ASFV). This protein exhibits high homology with cellular decapping enzymes and thus can potentially remove the cap structure from the RNA body triggering degradation.  We show that this protein interacts with viral and cellular mRNAs in infected cells. This interaction results in decreased levels of both types of transcripts, agreeing with a putative role as virus-encoded decapping activity. We propose that the degradation of RNA triggered by this protein is key to control gene expression in ASFV infected cells.