In the “Dynamics of protein synthesis & RNA decay” lab we are interested in how cells tune protein production by adjusting the stability of messenger RNAs (mRNAs). Each cell in our body expresses around 12,000 different mRNAs at any given time. To control this complex transcriptome—and thus protein synthesis—cells adjust half-lives for individual mRNAs from minutes to several days. Traditionally, the selective degradation of mRNAs has been attributed to the recognition of nucleotide sequence elements by proteins or small RNAs that subsequently recruit decay factors. In our lab, we investigate a distinct, newly emerging paradigm of gene regulation termed “peptide-mediated mRNA decay” (PMD). In PMD, not the mRNA sequence but rather the nascent protein is recognized to trigger degradation of the encoding mRNA during its translation by the ribosome. 

This process is exemplified by tubulin mRNAs, which are selectively degraded when cells sense excess free tubulins, the building blocks of the microtubule cytoskeleton. Perturbed tubulin mRNA turnover results in severe phenotypes, such as cell division defects, impaired neurodevelopment, ciliopathies, and infertility. Beyond tubulins, emerging evidence points to critical PMD mechanisms targeting transcripts encoding aggregation-prone proteins when crucial chaperones are absent. Thus, PMD represents an unexplored paradigm of gene regulation that dynamically adjusts protein production to ensure cellular fitness. However, a mechanistic understanding of peptide-mediated mRNA decay is only beginning to emerge, and the scope of PMD substrates is completely unknown. 

Using a highly interdisciplinary approach spanning biochemistry, structural biology, cell biology, genetics, and advanced sequencing methods, we aim to answer the following questions: What are the factors and molecular mechanisms driving peptide-mediated mRNA decay? How are these mechanisms controlled, and what are the consequences of impaired mRNA turnover for cells and organisms? What is the transcriptome-wide scope of regulation by peptide-mediated mRNA decay?

Answering these questions will be highly relevant to human biology and disease, as highlighted by the examples of tubulin and aggregation-prone proteins regulated by PMD. Furthermore, insights into mRNA decay mechanisms will enable development of optimized mRNA-based therapeutics like mRNA vaccines. 

Additional information can be found on the lab website: 

https://www.crg.eu/en/programmes-groups/hopfler-lab

Whom would we like to hire?  

Professional experience  

Must Have

• Lab experience with mammalian cell culture and common techniques in biochemistry, cell & molecular biology

• The candidate should hold a PhD degree, preferably in cell/molecular biology or biochemistry, OR a bachelor's/master's degree/vocational training and 3+ years work experience in these fields 

• Radioactivity facility operator license, OR willingness to obtain such a license within the first year 

Desirable but not required/ Nice to have

• Experience with project support and common laboratory task management

• Experience in biochemistry, RNA biology and/or microtubule biology 

• Ability to pursue research projects independently

• Experience with protein purification, next-generation sequencing or genetics approaches 

• Experience with handling and managing radioactive reagents

Languages

• Fluency in English 

• Spanish language may be needed to adhere to and implement local health and safety regulations 

Computer skills 

• Advanced MS Office experience 

• Skilled with data analyses software, e.g. Prism 

• Experience with electronic lab notebooks and other lab managing software is an advantage

Competences  

• Rigor, organization and autonomy 

• Strong analytical, interpersonal, and communication skills 

• Curiosity and critical thinking

The Offer – Working Conditions 

• Contract duration:  An initial contract will be offered for 1 year. It is anticipated that the contract will be extended linked to the activity of the lab (estimated October 2030).

• Estimated annual gross salary: Salary is commensurate with qualifications and consistent with our pay scales 

• Target start date: July 2024.   

We provide a highly stimulating environment with state-of-the-art infrastructures, and unique professional career development opportunities. To check out our training and development portfolio, please visit our website in the training section. 

We offer and promote a diverse and inclusive environment and welcome applicants regardless of age, disability, gender, nationality, ethnicity, religion, sexual orientation or gender identity.

The CRG is committed to reconcile a work and family life of its employees and are offering extended vacation period and the possibility to benefit from flexible working hours.

Application Procedure

 
All applications must include:

1. A motivation letter addressed to Dr. Markus Höpfler. 

2. A complete CV including contact details. 

3. Contact details of two to three referees. 

All applications must be addressed to Dr. Markus Höpfler and be submitted online on the CRG Career site - http://www.crg.eu/en/content/careers/job-opportunities  

Selection Process

• Pre-selection: The pre-selection process will be based on qualifications and expertise reflected on the candidates CVS. It will be merit-based. 

• Interview: Preselected candidates will be interviewed by the Hiring Manager of the position and a selection panel if required. 

• Offer Letter: Once the successful candidate is identified the People department will send a Job Offer, specifying the start day, salary, working conditions, among other important details.  

Deadline: Please submit your application before 26/06/2025.