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PhD position - Determining protein structures and understanding biology using deep mutagenesis

PhD position - Determining protein structures and understanding biology using deep mutagenesis

The Institute

The Centre for Genomic Regulation (CRG) is an international biomedical research institute of excellence, based in Barcelona, Spain, with more than 400 scientists from 44 countries. The CRG shares principles of an interdisciplinary, motivated and creative scientific team that is supported by high-end and innovative technologies and a flexible and efficient administration.

CRG has been conferred with a badge of ‘HR Excellence in Research’ by the European Commission, in recognition to its progress in implementing the European Charter for Researchers and the Code of Conduct for Recruitment of Researchers, that among others consists of transparent, merit-based recruitment procedures and attractive work-life balance working conditions.

For further information: www.crg.eu

The role

1 PhD position open to work in the Genetic Systems Lab at CRG, Barcelona.

About the team/ lab/ department

The Genetic Systems lab which is part of the CRG Systems Biology program,has recently demonstrated that it is possible to determine the 3D structures of proteins by quantifying the effects of a very large number of mutations in parallel using selection and sequencing. This genetic approach to structure determination relies on the quantification of unexpected interactions (genetic interactions or epistasis) between mutations and provides a new experimental strategy for structure determination, with the exciting potential to reveal the in vivo structures of molecules (Schmiedel + Lehner, Nature Genetics, in press, https://www.biorxiv.org/content/10.1101/303875v2). We are currently developing generic assays to use this approach to solve protein structures and are applying it to diverse areas of biology. For example, we are using the approach to understand the mechanisms by which proteins involved in neurodegeneration kill cells as well as the in vivo conformations of these ‘unstructured’ proteins (https://www.biorxiv.org/content/10.1101/592121v1).

More generally, we are using deep mutagenesis to address fundamental questions in genetics and to understand how mutations affect diverse molecular processes, including individual proteins and RNAs (https://www.nature.com/articles/s41586-018-0170-7), physical interactions (https://elifesciences.org/articles/32472), regulatory interactions (https://www.biorxiv.org/content/10.1101/578419v2), alternative splicing (https://www.cell.com/cell/fulltext/S0092-8674(18)31624-6), and gene networks (https://www.biorxiv.org/content/10.1101/589606v1). We are particularly interested in how mutations interact, the causes of global and specific genetic interactions, how genetic interactions reveal molecular mechanisms, the problem of accurate genetic prediction, and the evolutionary implications of all of this. The other two main interests of the lab are mutation and selection in cancer genomes (Cell 2017, Nature 2015) and the importance of noise and inter-generational epigenetics in phenotypic variation (eLife 2019, Nature 2017, Science 2017).

The lab (currently ~12 members) is highly collaborative with a flat structure and works with many different systems and approaches, including model organisms and human genetic data, choosing the system and approach for the question at hand. This creates a highly inter-disciplinary environment with many members of the lab using both experimental and computational approaches. All lab members lead their own projects. To date, 12 alumni from the lab have started their own labs, including in some of the most prestigious institutes in Europe and elsewhere.

Whom would we like to hire?

We are looking for a new PhD student to join the lab to take on one of these exciting projects involving deep mutagenesis.

The ideal candidate will be passionate about biology, motivated, organized and hard working with a ‘can do’ attitude.

  • You hold a a University Degree and a Masters Degree in a field of life sciences, engineering and/or physics within the European Higher Education System (minimum 300 ECTS)
  • You have substantial research experience in both molecular and computational biology
  • You are fluent in English

The successful applicant will enroll in the very active CRG International PhD program, which includes science and practical courses, a wide range of complementary skills training, access to many courses, mentoring via a thesis committee, and active participation in the organization of seminars, symposia and retreats.

The Offer

  • Contract duration: 4 year Phd Position
  • Estimated annual gross salary: Salary is commensurate with qualifications and consistent with our pay scales.

We provide a highly stimulating environment with state-of-the-art infrastructures, and unique professional career development opportunities.

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

Application Procedure

Applications are accepted exclusively online. Please, do it through the following link :


Candidates may contact imma.falero@crg.eu for informal enquiries regarding the application and academic enquiries, as well as address scientific enquiries to ben.lehner@crg.eu.

Deadline: June 16th, 2019