EastBio: Novel aptamer-based PET Imaging Tracer for TDP-43 Proteinopathies

Details

This fully funded, 4-year PhD project is part of a competition funded by the BBSRC EASTBIO Doctoral Training Partnership.

Aggregation of TAR DNA-binding protein 43 (TDP-43) is a pathological hallmark of several neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alzheimer’s disease (AD), and limbic-predominant age-related TDP-43 encephalopathy (LATE). Despite its central role in disease pathogenesis, the ability to visualise TDP-43 pathology in vivo remains a major unmet clinical need. While positron emission tomography (PET) has transformed the diagnosis and monitoring of several proteinopathies, no clinically approved PET tracer for TDP-43 currently exists. Only one candidate tracer, [¹⁸F]-ACI-19626 (AC Immune), has entered clinical evaluation. The absence of a reliable TDP-43 imaging biomarker limits early diagnosis, patient stratification, disease monitoring, and assessment of emerging therapies.

We have recently developed a proprietary high-affinity aptamer that selectively recognises pathological TDP-43 aggregates with greater sensitivity and specificity than conventional antibodies. This innovative molecular probe enables detection of early aggregation events and correlates with TDP-43 loss-of-function signatures. Importantly, these pathological changes can be identified before the onset of clinical symptoms, highlighting the aptamer’s potential as an early diagnostic tool.

This project aims to exploit the unique molecular recognition properties of this aptamer to develop a first-in-class PET tracer for TDP-43 proteinopathies. The aptamer, together with chemically modified analogues, will be functionalised and radiolabelled with clinically relevant positron-emitting radionuclides such as fluorine-18 or gallium-68 to generate novel radiopharmaceuticals capable of selectively targeting pathological TDP-43 aggregates.

The successful candidate will work at the interface of radiochemistry, medicinal chemistry, and neuroscience to:

1. Conjugate the aptamer and optimised derivatives with PET-compatible chelators (e.g. DOTA, NOTA) or fluorine-18 labelling handles.
2. Evaluate the stability of non-radioactive conjugates in serum and relevant in vitro models.
3. Optimise gallium-68 and fluorine-18 radiolabelling procedures and assess radiochemical yield and purity.
4. Investigate radiotracer stability in biologically relevant media, including artificial cerebrospinal fluid and serum.
5. Validate tracer affinity, selectivity, and specificity using pathological TDP-43 aggregates isolated from human post-mortem tissue and biofluid samples.

The project offers multidisciplinary training in radiochemistry, organic and medicinal chemistry, translational neuroscience, and diagnostic innovation, including radiosynthesis, analytical characterisation (NMR, HPLC), human tissue analysis, digital pathology, image analysis, and translational commercialisation.

By combining cutting-edge aptamer technology with molecular imaging, this research has the potential to transform the diagnosis and monitoring of TDP-43 proteinopathies. A selective TDP-43 PET tracer would enable earlier disease detection, improve patient stratification in clinical trials, and accelerate the development of targeted therapies for currently incurable neurodegenerative disorders.

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 16th November 2026 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 (University education only)
• 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 16th November 2026.

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

• You may only apply for one EastBio Project.
• No research proposal is required.
• Do not include any additional documents (for example, school certificates, conference papers, or dissertations).
• Incomplete applications or those including superfluous unnecessary documents 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.
• We will confirm receipt of your applications upon processing. Due to the high volume of applications, this may not be until after the deadline. We ask that you please refrain from contacting us regarding updates or to see if your application has been received.
• For any questions or assistance with the application process, please contact smmsn-pgrenquiries@abdn.ac.uk.

Funding Notes

This fully funded, four-year PhD project is offered as part of a competition within the EASTBIO BBSRC Doctoral Training Partnership. The opportunity is open to both UK and international applicants, although the proportion of international students recruited through the EASTBIO DTP is capped at 30% by UKRI BBSRC.

EASTBIO studentships provide a tax-free UKRI doctoral stipend (estimated at £22,437 for the 2027/28 academic year), a training grant of £5,000 per year for the first three years (and £1,500 in the fourth year), and a travel and conference allowance of £230 per year.

Please note that EASTBIO is unable to fund visa costs or associated healthcare surcharges for international students.