Postgraduate research opportunities Next-generation RNA-PROTACs: development of a direct-to-biology discovery platform for the targeted degradation of RNA-binding proteins
ApplyKey facts
- Opens: Monday 19 October 2026
- Number of places: 1
- Duration: 42 months
- Funding: Equipment costs, Home fee, Stipend
Overview
Lin28A and Lin28B are RNA-binding proteins that drive tumour progression, but the development of small molecule inhibitors has proved challenging. This studentship will develop RNA-PROTACs that will degrade Lins28A/B rather than simply inhibiting their function. You will build a direct-to-biology (D2B) platform that synthesises and tests degraders in a high throughput plate-based format, and use it to develop potent and selective Lin28 degraders that work without transfection.Eligibility
A first or an upper second-class (2:1) UK Honours degree, or overseas equivalent, in chemistry, chemical biology, biochemistry, pharmaceutical sciences or a closely related discipline is required. If English is not your first language, you must have an IELTS score of at least 6.5, with no component below 5.5. Because the award is funded at the Home fee rate, the studentship is open to applicants eligible for Home (Scottish) or Rest of UK fee status.
Experience in any of the following is desirable, although full training will be provided:
- synthetic organic or medicinal chemistry
- oligonucleotide or bioconjugate chemistry
- HPLC purification and LC–MS analysis
- mammalian cell culture; molecular or cell biology
We are looking for a motivated and collaborative student who enjoys working at the interface of chemistry and biology and is willing to learn techniques outside their first discipline.
Project Details
Around 15% of human cancers express Lin28, a class of RNA-binding proteins associated with poor prognosis. Lin28 blocks maturation of the let-7 tumour-suppressor microRNAs (miRNAs). Depletion of Lin28 restores let-7 miRNA levels and suppresses tumour cell proliferation and stemness. Despite strong genetic validation, no small-molecule inhibitor of either paralogue, Lin28A or Lin28B, has been identified. Both paralogues possess RNA binding motifs that bind to RNA through shallow, solvent-exposed surfaces which are difficult to develop small molecular inhibitors.
Targeted protein degradation offers a way to overcome the limitation of small molecule intervention. An RNA-PROTAC links an oligonucleotide that mimics the protein's natural RNA ligand with a small molecule that recruits an E3 ubiquitin ligase, marking the protein for degradation. Because degradation is catalytic, it does not demand the sustained, tight binding essential for small molecular inhibitors.
The project
This studentship will develop a direct-to-biology (D2B) platform in which RNA-PROTACs are assembled and assayed in cells in the same microtitre plate, without purification. The student will explore the utility of the D2B platform to vary the three modules of the degrader in parallel (i.e., the RNA-binding oligonucleotide, the linker and the E3 ligase binder) and establish how each module influences cell uptake, degradation potency and selectivity between the two Lin28 paralogues.
The specific aims of the project are to:
- establish nanoscale ligation chemistry to prepare RNA-PROTACs
- define the minimal oligonucleotide length and structure required for Lin28 binding and combine these in a plate-based screen of oligonucleotide × linker × E3 ligase binder combinations to identify potent, paralogue-selective degraders of Lin28A and Lin28B
The intended outcome is to establish the first combinatorial structure-activity map for an RNA-PROTAC, together with the identification of transfection-free degraders that discriminate between Lin28A and Lin28B.
Training
This is an interdisciplinary project spanning synthetic and nucleic acid chemistry, bioconjugation, automation and cell biology. You will be trained in solid-phase oligonucleotide synthesis, bioconjugate and medicinal chemistry, liquid-handling automation and high-throughput plate-based workflows, LC-MS analysis, mammalian cell culture and quantitative protein degradation assays. You will join a group with an established track record in nucleic acid chemistry and D2B degrader discovery with close links with GSK. This studentship will be integrated into a wider cohort of PhD and post-doctoral researchers associated within our Strathclyde-GSK EPSRC-funded Prosperity Partnership (UKRI1372).
Further information
The successful applicant will be expected to spend at least 3 months working alongside chemical biology groups at GSK's Stevenage site.
Funding details
The studentship is fully funded for 42 months and covers tuition fees at the Home (UK) rate, an annual tax-free stipend at the standard UKRI rate.
While there is no funding in place for opportunities marked "unfunded", there are lots of different options to help you fund postgraduate research. Visit funding your postgraduate research for links to government grants, research councils funding and more, that could be available.
Apply
Applications are considered on a rolling basis, and the advert will remain open until the position is filled. Early application is strongly encouraged. The expected start date is July 2027.
For further enquiries and application procedures, please email Glenn Burley (glenn.burley@strath.ac.uk) with an up to date academic transcript, CV and email contact details for two referees.
Number of places: 1
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