Epigenetic Origami: Folding the bromodomain proteins of Leishmania

FUNDING: 10 weeks (full time, 37 hrs per week, £10.57 per hour, £900 consumables)
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Dr Nathaniel Jones, Biology, York

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The production of recombinant proteins is a critical step that underlies many biotechnology and drug discovery programmes. However, using non-homologous systems, such as E. coli, can lead to difficulties in obtaining properly folded and functional protein samples. We have developed a new solubility-enhancement tag that stabilises and improves expression of challenging protein targets. This project will use the new tag system to produce recombinant Leishmania bromodomain proteins. These epigenetic reader proteins are essential for this human parasite, which causes ~1 million cases of leishmaniasis per year, and are under investigation as drug targets for new anti-leishmanials. The student will produce recombinant protein in E. coli, using the new solubility-enhancement tag, and compare them to samples made using standard approaches. The student will be trained in and apply biophysical methods such as SEC-MALLS, thermal stability shift, microscale thermophoresis, NMR spectroscopy and fluorescence-polarisation assays. This project is targeted at students interested in gaining experience in biochemical, structural biology or biophysical techniques in a drug discovery context.  Students will be expected to present their findings orally at a research day in York in September 2023.