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How to continue working as a PhD student during a global pandemic?

12 July 2021

Working as a PhD student during the global Covid-19 pandemic can be quite a challenge. Social distancing, wearing of facemasks and maximal occupancy rules for laboratories make achieving the aims of PhD research projects quite a task.

However, this was not the case for PhD students Jiaqi Lou, Shumeng Ma, Xinyue Shi, Qian Wang, Danni Dong and Shymaa Damfo at UCL School of Pharmacy. To advance their PhD projects they decided to switch their focus to potential drug targets from SARS-CoV-2, the coronavirus causing Covid-19, with the aim of discovering molecules that could inhibit viral replication. They decided to use a range of state-of-the-art techniques including fragment-based screening using x-ray crystallography and structure-based drug design.

Crucially, they found an open beamline at the EMBL/ESRF in Grenoble, France, where x-ray diffraction data for protein crystals could be measured. This facility continued to work during the pandemic and cleared some of its schedule to help with Covid-19 research projects. It remained open because it is highly automated, allowing high throughput measurements including automated crystal mounting and centring in the x-ray beam, automated data collection and processing, protein structure determination, initial refinement and in certain cases the automated identification of fragments bound to the SARS-CoV-2 protein targets.

The students were able to submit crystals to be measured remotely day and night in large batches of 200, without the need to be present. So far, the group has successfully identified several fragment hits, which now serve as starting points for the development of more potent analogues and hopefully will contribute to worldwide discovery efforts.

Watch the EMBL video explaining this exciting procedure and find out more through the links below.

YouTube Widget Placeholderhttps://www.youtube.com/watch?v=TAeelib8Vvg

 

    Publications:

    • Rogstam A., Nyblom M., Christensen S., Sele C., Talibov V.O., Lindvall T., Rasmussen A.A., André I., Fisher Z., Knecht W., Kozielski F. (2020). Crystal Structure of Non-Structural Protein 10 from Severe Acute Respiratory Syndrome Coronavirus-2. Int. J. Mol. Sci. 21, 7375.
    • Kozielski F., Sele C., Talibov V.O, Lou J., Dong D., Wang W., Shi X., Nyblom M., Rogstam A., Krojer T., Fisher Z., Knecht W. (2021). Identification of fragments binding to SARS-CoV-2 nsp10 reveals ligand-binding sites in conserved interfaces between nsp10 and nsp14/nsp16. Manuscript submitted.

    Contact:

    Prof Frank Kozielski, f.kozielski@ucl.ac.uk

    Further information: