This is a full-time, fixed term 4 year position on Crick terms and conditions of employment.
We seek a talented and motivated scientist who will work within Dr Ian Taylor’s “Macromolecular Structure laboratory” (https://www.crick.ac.uk/research/labs/ian-taylor). Dr. Taylor’s group is focussed on the structural biology of retroviruses and host-retrovirus interactions and aims to understand how retroviruses replicate, assemble and interact with host factors and defence proteins in human disease. The group applies a multidisciplinary approach encompassing structural-biology, biophysics and protein chemistry employing techniques ranging from X-ray crystallography, NMR and cryo-electron microscopy to SAXS, analytical ultracentrifugation, optical spectroscopy and protein chemistry.
For this project, the post-holder will apply state-of-the-art X-ray crystallographic and cryo-EM methods to examine allostery, catalysis and the interaction of drugs with the HIV-1 restriction factor SAMHD1. SAMHD1 blocks HIV-1 infection of myeloid cells by imposition of a nucleotide blockade through a GTP-dependent deoxynucleoside triphosphatase activity that reduces the dNTP pool to a level that cannot support viral reverse transcription. In our recent studies (Morris et al 2020, Nat commun 11, 3165; Morris et al 2021, Biochemistry 60, 1682) we have begun to unpick the molecular details of the catalytic mechanism of SAMHD1 dNTP hydrolysis.
For this Crick core-funded project, the post-holder will be expected to carry out independent research focused on the structural and mechanistic characterisation of SAMHD1. Specific objectives will include, but not be limited to:
- The post-holder is expected to work on a multidisciplinary project aimed at examining structural transitions in SAMHD1 throughout the catalytic cycle.
- The post holder will be responsible for developing biochemical and biophysical techniques to examine the interaction of SAMHD1 with substrate, allosteric activators and drug molecules.
- The post-holder will work in close collaboration with Dr Kate Bishop’s laboratory at the Crick (https://www.crick.ac.uk/research/labs/kate-bishop) who are examining the cellular and virological aspects of SAMHD1 restriction.
The post holder should embody and demonstrate our core Crick values: Bold, Imaginative, Open, Dynamic and Collegial, in addition to the following
- PhD in the area of either biophysics or structural biology.
- Comprehensive skills in molecular biology, protein expression and purification.
- Familiar with cryo-EM or X-ray data collection and structure refinement methodologies for structural biology.
- Experience of writing papers as evidenced by publications or submitted manuscripts in internationally recognized scientific journals.
- Ability to work independently and also capable of interacting within a group
- Good understanding of enzymology and assay development.
- Experience in biophysical analysis of protein and/or protein-nucleic acid complexes.
- Basic understanding of retrovirus replication.