Probing Protein-DNA transactions involved in DNA recombination and antibiotic resistance dissemination

A postdoc position is available right now in the groups of David Alsteens and Bernard Hallet at the Louvain Institute of Biomolecular Science and Technology (LIBST-UCLouvain, Belgium) to work on nucleoprotein complexes dynamics and protein-DNA transactions using state-of-the-art biochemistry and atomic force microscopy (AFM).

Protein-DNA transactions are involved in many biologically important processes such as DNA replication, repair and recombination, or the control of gene expression. In all cases, these processes require the assembly of elaborate nucleoprotein complexes whose architecture and dynamics usually escape traditional methods of investigation.

In particular, transposons (Tns) are ubiquitous genetic elements that can move from one place to another within the genome of their host. In human, they contribute for nearly half of genomic DNA, therefore acting as the architects of our chromosomes and the organization of regulatory networks. In bacteria, transposons are responsible for the emergence and dissemination of antibiotic resistances among pathogens, which continuously challenges the development antimicrobial therapies. In spite of this biological and societal impact, the molecular mechanisms that are used by these elements to move and propagate have remained largely elusive.

Our recent work on the bacterial transposon Tn4430has opened new avenues toward the understanding of these mechanisms. For the first time, we have been able to set up sensitive biochemical assays recapitulating key transposition steps of this elements. This work identified different protein-DNA complexes corresponding to different intermediates of the reaction (Nicolas et al., 2017, PNAS, 114: E669-78, doi: 10.1073/pnas.1611701114). The aim of this project is to further characterize the assembly and conformational dynamics of these complexes using state-of-the-art biochemistry and most advanced AFM technology (including AFM-based force spectroscopy). This project is also complementary to an ongoing work aiming at solving the atomic structure of the complexes by single-particle cryo-electron microscopy (SP Cryo-EM).

This study should prove to be pioneering in the protein-DNA transaction field.

Position is available to both foreign nationals and Belgian citizens under ‘international mobility’ status, meaning that they may not have resided in Belgium for more than 12 months over the past 3 years preceding the appointment. Initial duration is 12-15 months starting on the date of appointment, ideally before 01/07/2019

Candidates must have a PhD with a strong background in biochemistry and molecular biology. Expertise in the field of DNA recombination, protein-DNA interaction and nucleoprotein complex biochemistry is a valuable asset. Additional experience in AFM and AFM-based force spectroscopy is not mandatory. Priority will be given to candidates with a proven track record (with one or more publication as a first author) who will express their motivation in developing their autonomy and their interest for new challenges.

Interested applicants should send a cover letter (briefly describing research experience, interests, and career goal), a curriculum vitae (with list of publications), and the names of three references (With address, phone number and E mail) to Bernard HALLET (Bernard.hallet@uclouvain.be) & David ALSTEENS (david.alsteens@uclouvain.be)