This fully funded, 4-year PhD project is part of a competition funded by the BBSRC EASTBIO Doctoral Training Partnership.
TAR DNA-binding protein 43 (TDP-43) aggregation is a pathological hallmark of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alzheimer’s disease (AD) and limbic-predominant age-related TDP-43 encephalopathy (LATE)1,2. Despite its central role in disease pathogenesis, in vivo imaging of TDP-43 remains a major unmet need.3,4 Among the in vivo imaging modalities, Positron Emission Tomography (PET), is a non-invasive technique that enables the visualisation and quantification of physiological and biochemical processes, providing functional images. Today, no PET probes are clinically available to image TDP-43, and only one, showing the ability to bind to TDP-43, is in clinical trial ([18F]-ACI-19626, AC Immune)5. This slow development is hindering early diagnosis, patient stratification, and therapeutic monitoring.
Professor Jenna Gregory and colleagues have recently developed a high-affinity RNA aptamer (TDP-43APT) that can selectively bind pathological TDP-43 aggregates with greater sensitivity and specificity than conventional antibodies.6 This aptamer has revealed early nuclear aggregation events and correlates with loss-of-function signatures, such as STMN2 cryptic splicing, in both CNS6 and non-CNS7 tissues, preceding clinical symptom onset6
In this project, we plan to exploit the unique binding properties of the TDP-43APT aptamer to develop an innovative and selective PET imaging tracer for TDP-43 by radiolabelling it with a suitable positron-emitting radioisotope. (e.g., fluorine-18 or gallium-68).
In this interdisciplinary project, the candidate will
- conjugate TDP-43APT (or modified analogues) with PET-compatible chelators (e.g., DOTA, NOTA) or with chemical handles able to quickly bind with fluorine-18 prosthetic groups.
- Assess the stability of non-radioactive compounds in serum and in vitro.
- Evaluate the radiolabelling efficiency for gallium-68 and optimise the radiosynthesis with fluorine-18 derivatives.
- Confirm the stability of the radiopharmaceutical derivatives in biological substrates such as artificial CSF/serum matrix.
- Validate the binding specificity and affinity to disease-relevant pathological TDP-43 aggregates in a more physiological setting using aggregates extracted from human post-mortem tissue and biofluid specimens.
The successful candidate will receive a truly multi-disciplinary training experience in radiochemistry (manual and automated radiosynthesis; purification of radiotracers), organic chemistry (synthesis and analysis i.e. NMR, HPLC, etc) and translational medicine/neuroscience (human tissue handling, aptamer staining, digital image analysis, data analysis), as well as understanding the commercial landscape of translational diagnostics.
Overall, this work has the potential to transform the diagnostic landscape for TDP-43 proteinopathies and accelerate the development of targeted therapies by leveraging the unique molecular recognition capabilities of the TDP-43APT aptamer.
This project is available for part-time study (Home/UK students only).
Interested applicants should contact the lead supervisor to discuss the project prior to applying. You can do this by selecting the first listed name at the top of this advert and sending your enquiry. Alternatively, you can search for the supervisor through the University of Aberdeen staff directory and email them directly.
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ELIGIBILITY:
Applicants should hold a minimum of a 2:1 UK Honours degree (or international equivalent) in a relevant subject. Those with a 2:2 UK Honours degree (or international equivalent) may be considered, provided they have (or are expected to achieve) a Distinction or Commendation at master’s level.
We encourage applications from all backgrounds and communities, and are committed to having a diverse, inclusive team.
All students must meet the eligibility criteria as outlined in the UKRI guidance on funding for postgraduate training and development. This guidance should be read in conjunction with the Terms and conditions for training funding – UKRI.
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APPLICATION PROCEDURE
For full details and to download the application form, visit: https://biology.ed.ac.uk/eastbio/how-to-apply
Please note that you may only apply for one EASTBIO project.
1. Application submission
Submit your complete application by 23:59 GMT on 15th December 2025 to smmsn-pgrenquiries@abdn.ac.uk.
Send your application as a single email with the subject line:
“EASTBIO Application – [Your Name]”
2. Required documents
Your application email must include the following:
- Completed EASTBIO application form
- Academic certificates and transcripts
- Two references (one reference may be non-academic)
3. References
All references must be provided using the official EASTBIO reference form (available here).
References can be either:
- Included with your application, or
- Sent directly by referees to smmsn-pgrenquiries@abdn.ac.uk with the subject line: “EASTBIO Reference – [Your Name]”
All references must be received by 23:59 GMT on 15th December 2025.
It is the applicant’s responsibility to ensure both references are submitted by the deadline, as we cannot request them on your behalf.
Important notes
- No research proposal is required.
- Do not include any additional documents (for example, school certificates, conference papers, or dissertations).
- Incomplete applications or those including unnecessary materials will not be considered.
- Due to workload constraints, we are unable to follow up on missing documents or process incomplete applications.
- All candidates will be notified of the outcome of their application.
For any questions or assistance with the application process, please contact smmsn-pgrenquiries@abdn.ac.uk.
