Postdoctoral Training Fellow

Postdoctoral Training Fellows are expected to lead their own projects and collaborate within the lab and externally. The ability to work in a team is essential.

Key information

Job reference
R278
Salary
Competitive with benefits, subject to skills and experience.
Application close date
25 July 2021, 00:00 BST
Hours per week
36 (full time)
Number of positions
2
Posted 24 June 2021

Contact term: Two full-time, fixed-term (4 years) positions on Crick terms and conditions of employment.

Summary

The projects in the group involve structural studies of virus-host interactions and viral replication. Large part of the work in the laboratory is directed towards understanding the process of retroviral DNA integration, the mode of action of HIV integrase inhibitors and the mechanisms the virus uses to develop resistance to these drugs.

Examples of open research questions that align with the group's interests include how HIV integration machinery is affected by epigenetic status of chromatin, and what roles host cell factors play in this process. One of the goals will be to determine the structure of the lentiviral integration machinery, the intasome, in complex with chromatinized target DNA and host factors. Another challenging project will be to unravel the mechanism of intasome disassembly following integration. The particular goals and projects will be decided upon discussions with the successful applicants.

The main techniques used in the laboratory are cryo-electron microscopy and X-ray crystallography, supported by state-of-the-art facilities in the Institute. The Cryo-EM facility provides access to all necessary equipment, including two Titan Krios 300-kV microscopes each equipped with a Volta phase plate and Falcon III detector (one has an additional Gatan energy filter and K2 detector) and these are complemented by a Talos Arctica 200-kV instrument and a 120-kV Spirit TEM screening microscope. Cryo-EM data processing is carried out using in-house CPU/GPU cluster. The Crystallography facility harbours a wide range of high-end instrumentation, including two Rock Imager 1000s for high-throughput crystallization screening and optimization at two temperatures, two Formulator-16s, and an X-ray suite equipped with a Bruker D8 Venture X-ray diffraction system with an Excillum liquid MetalJet X-ray generator coupled to the latest photon counting detector producing a highly intense 75-mm beam that allows testing small crystal systems in-house and a fully automated crystal plate adapter capable of examining crystals in-situ.

Recent publications from the laboratory:

Rosa, A., et al. (2021). SARS-CoV-2 can recruit a heme metabolite to evade antibody immunity. Sci. Adv. 7, eabg7607; doi: 10.1126/sciadv.abg7607

Pye, V.E., et al. (2020). A bipartite structural organization defines the SERINC family of HIV-1 restriction factors. Nat. Struct. Mol. Biol. 27, 78-83; doi: 10.1038/s41594-019-0357-0

Cook, N.J., et al. (2020). Structural basis of second-generation HIV integrase inhibitor action and viral resistance. Science 367, 806-810; doi: 10.1126/science.aay4919

Lesbats, P., et al. (2017). Structural basis for spumavirus Gag tethering to chromatin. Proc. Natl. Acad. Sci. USA 114, 5509-5514. doi: 10.1073/pnas.1621159114

Ballandras-Colas, A., et al. (2017). A supramolecular assembly mediates lentiviral DNA integration. Science 355, 93-95. doi: 10.1126/science.aah7002

Maskell, D.P., et al. (2015). Structural basis for retroviral integration into nucleosomes. Nature 523, 366-369. doi: 10.1038/nature14495

The Institute

The Francis Crick Institute is a new research institute with an international reputation for cutting edge research into basic biology and is committed to training the next generation of research scientists.

The Francis Crick Institute is a biomedical discovery institute dedicated to understanding

the fundamental biology underlying health and disease. Its work is helping to understand

why disease develops and to translate discoveries into new ways to prevent, diagnose and

treat illnesses such as cancer, heart disease, stroke, infections, and neurodegenerative

diseases.

An independent organisation, its founding partners are the Medical Research Council (MRC),

Cancer Research UK, Wellcome, UCL (University College London), Imperial College London

and King’s College London.

The Crick was formed in 2015, and in 2016 it moved into a brand new state-of-the-art

building in central London which brings together 1500 scientists and support staff working

collaboratively across disciplines, making it the biggest biomedical research facility under a

single roof in Europe.

The Francis Crick Institute will be world-class with a strong national role. Its distinctive

vision for excellence includes commitments to collaboration; to developing emerging talent

and exporting it the rest of the UK; to public engagement; and to helping turn discoveries

into treatments as quickly as possible to improve lives and strengthen the economy.

Key responsibilities

Postdoctoral Training Fellows are expected to lead their own projects, contribute to other projects on a collaborative basis (both in the lab and with external collaborators) and help guide PhD and MSc students in their research.

The responsibilities include but are not limited to:

  • Investigating research questions and developing specific research project(s) under guidance from the group leader.
  • Providing specialist advice and guidance, sharing knowledge and expertise for the benefit of others.
  • Providing significant contribution to the production of research papers for publication, presenting findings to group members and other internal audiences.
  • Presenting work externally at international meetings.
  • Authoring papers under guidance from group leader.
  • Following Postdoctoral Training programme.
  • Developing academic independence.
  • Improving established protocols and/or develops new protocols.
  • May be required to guide others.

Key experience and competencies

The post holder should embody and demonstrate our core Crick values: bold, imaginative, open, dynamic and collegial, in addition to the following:

Essential

  • PhD (or in the final stages of PhD thesis submission) in biomedical sciences, biophysics, or medicinal chemistry.
  • Good knowledge of and experience in protein chemistry, recombinant protein production and purification.
  • Technical expertise in cryo-EM and/or X-ray crystallography, including data processing, model building and validation.
  • Track record of writing papers as evidenced by publications (or submitted manuscripts) in refereed journals.
  • Evidence of data presentation at scientific meetings.
  • Understanding of and experience in experimental design.
  • Ability to work independently while productively interacting within a group.
  • Independent thinking and drive to succeed.

Desirable

  • Experience with cell and viral culture.
  • Experience in in vitro nucleosome/chromatin assembly.
  • Experience in recombinant protein production in eukaryotic host systems.