(BBSRC NWD) Developing a vCLEM pipeline for high-resolution analysis of neurons of the Drosophila brain
- Funding
- Funded
- Study mode
- Full-time
- Apply by
- Start date
- Subject area
- Biological and Biomedical Sciences
As we age, our neurons become less efficient at transmitting messages. This decline can lead to overall quality of life and increased risk of neurodegenerative diseases. To understand these changes, exciting new imaging techniques are emerging that allow us to visualise neurons within the brain with incredible detail.
Volume electron microscopy (vEM) provides brain visualisation at the nanoscale in three dimensions (1). However, studying complex tissue volumes like the brain with this technique poses may challenges. A cutting-edge vEM technique overcoming these obstacles, is array tomography-scanning electron microscopy (AT-SEM). This method enables the capture of non-destructive images of ultra-thin slices of brain tissue, at different resolutions, on different microscopes. This hierarchical imaging is perfect for capturing rare events in complex tissue, like the brain (2).
This research project will focus on a model of brain ageing using the visual cortex of the fruit fly Drosophila, which shares many similarities with the ageing human brain (3). The project will investigate specific structures called axonal varicosities or swellings, that occur on aged axons. These swellings could signal early stages of neuronal decline and are seen in various neurodegenerative diseases. Unfortunately, we currently know little about their role and significance.
The aim of this project is to build on already established vEM techniques and develop immunofluorescence AT (IF-AT) (4) and AT-SEM for high-resolution analysis of axonal swellings within the Drosophila aged brain. Objectives, methods and plan of work are indicated below:
This inter-disciplinary project will provide broad training to the student: genetic manipulations; cell-culture of primary neurons, as starting samples for vEM, then moving towards in vivo studies (vulnerable skills); detail understanding of cell biology; multiple light microscopy and EM related techniques.
1. Samejima K, Gibcus JH, Abraham S, Cisneros-Soberanis F, Samejima I, Beckett AJ, Pucekova N, Abad MA, Spanos C, Medina-Pritchard B, Paulson JR, Xie L, Jeyaprakash AA, Prior IA, Mirnv LA, Dekker J, Goloborodko A and Earnshaw WC.
Rules of engagement for condensins and cohesins guide mitotic chromosome formation. Science 388, 6743 (2025) https://doi.org/10.1126/science.adq1709
2. Cisneros Soberanis F, Simpson E, Beckett AJ, Pucekova N, Prior IA, Booth DG and Earnshaw WG. Near millimolar concentration of nucleosomes in mitotic chromosomes from late prometaphase into anaphase. J Cell Biol 4 November 2024; 223 (11): e202403165. doi: https://doi.org/10.1083/jcb.202403165
3. Carter R, Milani M, Beckett AJ, Liu S, Prior IA, Cohen GM, Varadarajan S. Novel roles of RTN4 and CLIMP-63 in regulating mitochondrial structure, bioenergetics and apoptosis. Cell Death Dis 13, 436 (2022). https://doi.org/10.1038/s41419-022-04869-8
4. Okenve-Ramos P, Gosling R, Chojnowska Monga M, Gupta K, Shields S, Alhadyian H, Collie C, Gregory E, Sanchez-Soriano N. Neuronal ageing is driven by microtubule decay. (2024) PLOS Biol, Mar 13;22(3):e3002504. doi: 10.1371/journal.pbio.3002504. PMID: 38478582; PMCID: PMC10962844.
5. Hahn, I., Voelzmann, A., Parkin, J., Fuelle, J., Slater, P.G., Lowery, L., Sanchez-Soriano, N., Prokop, A. Tau, XMAP215/Msps and Eb1 jointly regulate microtubule polymerisation and bundle formation in axons. PLOS Genet. 2021. 17, e1009647ff. — https://doi.org/10.1371/journal.pgen.1009647
Applicants must have obtained or be about to obtain a minimum Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in an appropriate area of science, engineering or technology.
International applicants
We are only able to offer a limited number of full studentships to applicants outside the UK. Therefore, full studentships will only be awarded to exceptional quality international candidates due to the competitive nature of this scheme.
International applicants must ensure they meet the academic eligibility criteria (including English language) before applying. Visit our English Language requirements page to find out more.
Equality, Diversity and Inclusion
Equality, diversity and inclusion is fundamental to the success of The University of Liverpool, and is at the heart of all of our activities. The full equality, diversity and inclusion statement can be found on our website
The supervisory team at the University of Liverpool has complementary expertise. Prof. Ian Prior is the academic lead of the Biomedical Electron Microscopy Facility. Dr. Natalia Sanchez-Soriano is an expert in neurobiology and Drosophila models of brain ageing in vivo.
Contact the supervisory team for further information.
Browse our BBSRC NWD in Bioscience projects and discover one you’re passionate about that matches your interests, ambitions and goals.
Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application.
How to Apply
All applications should be submitted through the University of Manchester application portal.
Apply directly via this link, and select BBSRC DTP PhD as the programme of study. You may apply for up to two projects from the programme via this scheme. To do so, submit a single online application listing both project titles and the names of both main supervisors in the relevant sections.
Please ensure that your application includes all required supporting documents:
Incomplete or late applications will not be considered.
Applications should not be made through the University of Liverpool’s application portal.
You must submit your application form along with the required supporting documents by the deadline date. You can select up to two projects on one single application, noting the title of each project from the advert and the supervisor name. This can include two projects from one institution or a project from each institution.
Once you have completed your application, you’ll receive a confirmation email.
Deadline: Sunday 7th December, midnight (UK time)
Late or incomplete applications will not be considered.
If you need help with this stage of the process, or have any queries regarding your eligibility (such as if you achieved unexpectedly low degree results due to extenuating circumstances), please contact the Liverpool BBSRC team for advice at bbsrcdtp@liverpool.ac.uk
Finally, register and apply online. You'll receive an email acknowledgment once you've submitted your application. We'll be in touch with further details about what happens next.
Once you have applied through the University of Manchester portal, and if you are successfully offered a studentship following a formal interview, you will be instructed to apply formally through the University of Liverpool. You must only do this once you have been instructed to do so.
Your tuition fees, funding your studies, and other costs to consider.
Fees stated are for the 2025/26 academic year. Tuition fees for the academic year 2026/27 will be announced soon.
We understand that budgeting for your time at university is important, and we want to make sure you understand any costs that are not covered by your tuition fee. This could include buying a laptop, books, or stationery.
Find out more about the additional study costs that may apply to this project, as well as general student living costs.
These studentships are available to UK and international applicants, and provide funding for tuition fees and stipend at the UKRI rate, subject to eligibility, for four years. This does not include any costs associated with relocation. This scheme is open to both UK and international applicants.
Have a question about this research opportunity or studying a PhD with us? Please get in touch with us, using the contact details below, and we’ll be happy to assist you.