Illuminating the Plasmodium apicoplast genome organisation

Details

We invite applications for a PhD research project to study organellar protein-DNA interactions in human pathogens. The project will answer mechanistic questions about organellar genome organisation with downstream translational implications in combatting antimicrobial resistance.

Plasmodium, the causative agent of malaria, harbours an essential non-photosynthetic plastid called the apicoplast. Just like mitochondria, apicoplast has its own genome and maintenance and compaction of the apicoplast DNA is essential for Plasmodium survival. Apicoplast genome is compacted by a prokaryotic histone like protein called HU. Sequence analysis reveals that the apicoplast HU has some major differences when compared to prokaryotic HU and our initial biochemistry shows that apicoplast HU uses unique mechanisms for apicoplast DNA compaction. In this collaborative, inter-disciplinary project, we will use cryo-EM (Lahiri lab https://sites.google.com/sheffield.ac.uk/lahirilab/), NMR (Willamson lab https://sites.google.com/sheffield.ac.uk/williamson/research?authuser=0) and single molecule biophysics (Newton lab https://www.sheffield.ac.uk/biosciences/people/academic-staff/matt-newton) to delineate the molecular mechanism of Plasmodium apicoplast genome organisation.

In addition to answering a long-standing fundamental question, namely, how is organellar genome organised, the knowledge gained from this work will aid in downstream projects looking to develop inhibitors of apicoplast HU to combat multi-drug resistant Plasmodium.

Science Graduate School

As a PhD student in one of the science departments at the University of Sheffield, you’ll be part of the Science Graduate School. You’ll get access to training opportunities designed to support your career development by helping you gain professional skills that are essential in all areas of science. You’ll be able to learn how to recognise good research and research behaviour, improve your communication abilities and experience the breadth of technologies that are used in academia, industry and many related careers. Visit http://www.sheffield.ac.uk/sgs to learn more.

Please apply for this project using this link: https://www.sheffield.ac.uk/postgraduate/phd/apply/applying

Funding Notes

First class or upper second 2(i) in a relevant subject. To formally apply for a PhD, you must complete the University’s application form using the following link:

https://www.sheffield.ac.uk/postgraduate/phd/apply/applying

All applicants should ensure that both references are uploaded onto their application as a decision will be unable to be made without this information.

References

https://sites.google.com/sheffield.ac.uk/lahirilab/

https://sites.google.com/sheffield.ac.uk/williamson/research?authuser=0

https://www.sheffield.ac.uk/biosciences/people/academic-staff/matt-newton

https://www.biorxiv.org/content/10.1101/2025.04.09.647933v1.full