PhD in Drug Discovery: Investigating PROTAC-Mediated Phospholamban Degradation for Heart Failure Target Validation

PhD in Drug Discovery: Investigating PROTAC-Mediated Phospholamban Degradation for Heart Failure Target Validation

Assessment date: 4 November 2026
Recommendation: Promising with material uncertainties

Quick Decision

This is a cross-disciplinary chemical-biology and cardiac-physiology PhD at the University of Glasgow. It proposes to use proteolysis-targeting chimeras (PROTACs) to remove phospholamban (PLN), a small regulatory protein that inhibits the SERCA calcium pump, and train the student from compound design and synthesis through cellular assays. The combination is unusually coherent for applicants who want to work across medicinal/organic chemistry and cardiovascular molecular biology. The project is listed by Glasgow’s MVLS/EPSRC doctoral training programme for an October 2027 start, with interviews planned for late March 2027.

Three decision points need written clarification. First, Glasgow’s current programme page says tuition and a stipend of at least £21,805 for all students, while its eligibility page still shows the prior £20,780 2025/26 rate. The official wording includes international applicants but does not explicitly quantify whether the full international fee is covered or identify any fee-gap top-up; Glasgow lists the 2027/28 non-clinical MVLS research fee as £33,708. The 2027/28 stipend is not yet confirmed. Second, the project page is brief, and a Glasgow thesis awarded in 2024 has a closely related PROTAC–PLN title under the same supervisors; its abstract and thesis are not available in the repository. Ask what new work this studentship will add and what preliminary compounds or data already exist. Third, the closing time is 8 January 2027 at 23:45 UK time; the official page does not specify GMT/UTC. Check the portal and obtain the fee and deadline details in writing before deciding whether the funding is workable. Project page, MVLS/EPSRC programme, 2027/28 research fees, related Glasgow thesis.

Research Problem and Doctoral Work

What Is Unsolved and Why It Matters

In heart muscle, SERCA2a pumps calcium from the cytosol back into the sarcoplasmic reticulum, helping the cell relax and replenish calcium for the next contraction. Unphosphorylated PLN binds to and inhibits SERCA, lowering its calcium sensitivity; phosphorylation can relieve that inhibition. Calcium-handling changes are implicated in heart failure, but manipulating this system is not automatically beneficial: calcium signaling is involved in contraction, relaxation, metabolism and electrical stability, so interventions require careful measurement of both desired effects and potential arrhythmia or other off-target consequences. Cleary et al., 2024, Kho, 2023, Redel-Traub et al., 2025.

The project’s proposed intervention is to make cells degrade PLN with a bifunctional PROTAC, thereby releasing SERCA from PLN-mediated inhibition. This is a target-validation and chemical-biology strategy, not an established heart-failure treatment. Targeted protein degradation has reached clinical investigation in other therapeutic areas, but current reviews emphasize that degrader performance depends on target engagement, E3-ligase recruitment, cell context and the degradation mechanism; these general advances do not demonstrate that PLN can be selectively or safely degraded in a therapeutic setting. Project page, Tsai et al., 2024.

Work, Methods, and Potential Outputs

The advertised project gives a broad training arc rather than a detailed experimental protocol: the student will work from compound design and synthesis to cellular assay. The title and summary identify the target and biological premise, but the public description does not name the PLN-binding ligand, recruited E3 ligase, PROTAC architecture, synthetic route, specific cell model, assay endpoints, selectivity controls, quantitative degradation criteria, or whether work extends to animals. Do not assume that the PhD includes a particular model, clinical sample, in-vivo experiment or therapeutic candidate. Project page.

A useful research sequence to discuss with the supervisors would be: establish that candidate compounds bind or engage PLN; test whether they induce PLN degradation rather than merely alter PLN–SERCA binding; quantify time- and concentration-dependent target reduction and selectivity; measure SERCA function and relevant calcium-handling/cellular outcomes; then determine how robust those effects are across suitable cell contexts. This is an evidence-based interpretation of the broad project aim, not a promised work package. Ask which assays and controls have already been established, how the team will distinguish target degradation from functional inhibition, and what constitutes a meaningful cellular proof of concept.

The field presents several specific technical questions. PROTAC design depends on the geometry and stability of the target–degrader–E3 complex, availability of an appropriate ligand, target localization and effective cellular exposure. PLN is a small membrane-associated protein, so the practical route by which the chosen E3 machinery can reach it, and how degradation will be verified, deserves direct discussion. A 2024 Glasgow-led proof-of-principle study used Halo-tagged zDHHC enzymes and Halo-PROTACs; it found that the effect on substrate palmitoylation varied by cell line and could be buffered by other zDHHC enzymes. That is a useful local precedent for degrader and cell-context questions, but it does not establish an untagged PLN degrader or predict this project’s results. Bai et al., 2024.

A closely related University of Glasgow thesis, awarded in 2024 to Emily Kathleen Gallen under Will Fuller and David France, is titled PROTAC-mediated degradation of phospholamban as a novel therapeutic strategy for heart failure. The repository says the thesis is unavailable and provides no abstract. This is highly relevant context, but it does not show whether the new project is a direct continuation, whether the earlier work produced a viable molecule, or what the next student would inherit. Before applying or interviewing, ask what is new in the 2027 project and whether any structures, compounds, assays, negative results or preliminary data can be discussed. Glasgow thesis record.

School, Programme and Field Context

The degree opportunity is advertised by the University of Glasgow through its MVLS/EPSRC Doctoral Training Programme. The project names Will Fuller in the School of Cardiovascular & Metabolic Health and David France in the School of Chemistry. This is a Glasgow-based cross-college collaboration; no external degree-awarding institution or joint award is identified. The formal registering school, research-degree title, assessment route and any thesis-pending period should be confirmed in the offer. The listed funded period is 3.5 years; it should not be treated as proof of the total registration or writing-up period. University regulations require supervised independent research and training specified by the Graduate School, funder and supervisor. Project page, MVLS/EPSRC programme, Glasgow postgraduate research regulations.

Glasgow’s 2026 subject-ranking announcement reports 41st globally for Life Sciences & Medicine in the QS subject ranking and 48th for Medical & Health in the THE subject ranking. These are broad subject-group signals, not rankings of molecular pharmacology, chemical biology, the named laboratories or this project. REF 2021’s Clinical Medicine environment statement describes Glasgow’s MVLS as a cross-disciplinary biomedical college with clinical and biomedical institutes and translational research links. This indicates a broad institutional context; it does not establish that this experimental project has access to a particular clinic, patient cohort or translational facility. Glasgow subject rankings, 2026, REF 2021 Clinical Medicine environment statement.

The MVLS Graduate School describes access to multidisciplinary research, facilities, supervision and a broad transferable-skills programme. Its PGR Graduate Skills Pathway includes writing and presentation, information retrieval, statistics, research design and research ethics, with some topics required for progression. That is useful college-level provision, but the public project summary does not name the specific lab facilities, chemistry support, cardiac-cell models, compound-characterization methods or project-level collaborations reserved for this student. Ask what practical training is planned across the chemistry and cardiovascular groups and how the two supervisors divide day-to-day guidance. MVLS Graduate School, MVLS PGR registration and Graduate Skills Pathway.

Supervisor and Lab Assessment

Supervisor Research Directions

Will Fuller is Professor of Molecular Physiology in the School of Cardiovascular & Metabolic Health and directs its research and innovation. His group studies membrane proteins that regulate cardiac excitability, signaling and contraction, including calcium-handling proteins such as PLN. It combines biochemistry, electrophysiology, imaging and chemical biology, and lists both targeted degradation of cardiac proteins using PROTACs and PLN as a heart-failure therapeutic target among its current themes. The profile reports support from the British Heart Foundation, BBSRC and industrial partnerships. Will Fuller profile.

David France is a Reader in the School of Chemistry and leads a Chemical Biology & Organic Synthesis group. His profile describes organic-molecule synthesis and disease-focused interdisciplinary collaboration, including a heart-failure strategy with Fuller. The pairing gives the project an evident chemistry-to-cell biology structure. Neither profile specifies supervision frequency, the primary supervisor, laboratory-group size for this project, or which group owns the main compound-design, synthesis and assay work. David France profile.

Recent Important Publications

• Bai et al. (2024), “Targeted degradation of zDHHC-PATs decreases substrate S-palmitoylation,” PLOS ONE. The Glasgow team tested Halo-PROTAC-mediated degradation of tagged zDHHC enzymes. In one cell line, degradation changed palmitoylation of selected substrates; the same effect was not reproduced in a second cell line, and the authors discuss possible functional redundancy. This is the closest recent local methodological precedent for targeted degradation in membrane-protein biology. Its tag-dependent design and different targets mean it is not proof of a PLN degrader. Paper.
• Kuo et al. (2025), “Nanobody-thioesterase chimeras to specifically target protein palmitoylation,” Nature Communications. The Fuller-led study developed tools to manipulate post-translational modification on selected proteins. It showed altered CaV1.2 channel behavior and arrhythmia susceptibility in stem-cell-derived cardiac myocytes. This supports the group’s cardiac-cell assay and molecular-tool expertise, but the method removes palmitoylation rather than degrading PLN. Paper.
• Luptak et al. (2025), “State-selective small molecule degraders that preferentially remove aggregates and oligomers,” Nature Communications. France is a co-author of work on TRIMTAC small-molecule degraders that exploit TRIM21-mediated recognition of assembled protein targets. The study demonstrates a distinct degrader mechanism and state-selective activity; its protein targets and mechanism differ from the proposed PROTAC–PLN strategy. Paper.
• Howie et al. (2024), “Glutathione-dependent depalmitoylation of phospholemman by peroxiredoxin 6,” Cell Reports. The Fuller group links redox state and post-translational modification to phospholemman regulation of the cardiac sodium pump. It is relevant to the lab’s work on membrane-associated cardiac regulatory proteins and cellular physiology, not direct evidence for PLN degradation or SERCA activation. Paper.
• Cleary et al. (2024), “Phospholamban inhibits the cardiac calcium pump by interrupting an allosteric activation pathway,” Journal of Biological Chemistry. Using a SERCA biosensor, the authors tested PLN’s effects on calcium affinity with and without a non-hydrolysable ATP analogue and proposed that PLN interrupts an ATP-linked allosteric activation pathway. This sharpens the mechanistic question behind PLN removal; it does not test a PROTAC or establish its therapeutic effect. Paper.

Lab, Resources, and Collaboration Environment

The public pages establish two relevant research homes: cardiovascular molecular physiology and organic/chemical biology. Fuller’s profile names biochemical, electrophysiological and imaging approaches; France’s profile describes chemical synthesis and collaborations. Published local work has combined molecular tools with cardiac myocyte assays and PROTAC-like degraders in other targets. No source commits this studentship to a specific instrument, platform, lab allocation, animal facility, medicinal-chemistry service or commercial partner. The project’s specific prior Glasgow thesis and the listed prior Novo Nordisk-funded PLN-degradation project make a direct discussion of available compounds, assay systems, intellectual-property constraints and what results may be shared especially important. Will Fuller profile, David France profile, Bai et al., 2024, Glasgow thesis record.

Funding, Application, and Living Cost

The MVLS/EPSRC programme’s current page says applications opened 2 November 2026, the studentship starts in October 2027, and tuition fees plus a stipend of at least £21,805 are provided “for all students.” The project is listed within this programme; its duration is 3.5 years, and the eligibility page also states that the grant includes laboratory expenses for Home and International applicants. However, that eligibility page still gives £20,780, explicitly labelled the 2025/26 UKRI rate, whereas the current programme page and UKRI guidance give £21,805 for 2026/27. Treat the older eligibility-page figure as stale. The 2027/28 stipend remains unannounced in the checked sources. MVLS/EPSRC programme, eligibility, UKRI stipend guidance.

For an international applicant, the wording is promising but not definitive on the full fee rate: the programme says fees are provided for all students and the eligibility page says Home/International applicants, but neither specifies that the complete international rate will be paid, names the source of a top-up, or says whether any amount could remain payable by the student. Glasgow’s 2027/28 research-fee table lists £33,708 per year for non-clinical postgraduate research in the College of Medical, Veterinary and Life Sciences; the 2027/28 UK fee is still to be confirmed (the page gives £5,238 for 2026/27). Those are fee rates, not a written statement of this studentship’s payment arrangement. Glasgow also says that some projects may have a research-support/bench fee, with any amount specified in the offer letter; the eligibility page’s laboratory-expense wording does not settle whether this project has any separate charge. Request written confirmation of the funded international fee rate for each year and any bench fee or uncovered costs. Glasgow 2027/28 PGR fees, UKRI stipend and fee guidance.

The University’s international-student FAQ estimates living costs in Glasgow at £1,100–£1,700 per month, depending on accommodation and lifestyle. The current published UKRI minimum of £21,805 is about £1,817 per month; the simple difference against that broad estimate is approximately £117–£717 per month before visa and NHS surcharge, travel, deposits, equipment or personal circumstances. This is only a planning comparison: it assumes the 2026/27 rate, not the unconfirmed 2027/28 stipend, and the University’s range is not a project-specific budget. Glasgow international FAQ, UKRI stipend guidance.

Glasgow’s programme guidance estimates that international students should budget approximately £5,000–£6,000 for visa and NHS health surcharge over the 3.5-year PhD. Current GOV.UK pages list a £558 Student visa application fee and an IHS rate of £776 per year for students; the actual surcharge depends on the visa duration, which can extend beyond the funded research period. The University estimate and the current fee schedule do not provide a transparent itemized calculation, so confirm the total and keep a separate contingency. MVLS/EPSRC eligibility, Student visa fee, IHS rates.

Applications are submitted for the named project through Glasgow’s online application system, and every candidate must upload the MVLS/EPSRC Recruitment Form 2027. The programme says this is the only form used for shortlisting; applicants should include only the requested information on that form and omit identifying details such as name, gender, ethnicity, nationality and institutions attended or trained at. Add the online application number so the form can be matched to the application. Other required uploads listed on the official page are a CV, academic transcript, degree certificates, a personal statement of no more than one A4 page, a passport-page scan, two academic referee details, and English-language certification if applicable (the latter can be added later). The statement should cover relevant academic/professional experience, laboratory techniques and research projects, reasons for choosing the programme and expected benefits. Enter the project title in the portal’s Research Proposal section, but do not upload a research proposal; the page says one is not required despite the portal prompt. Applicants are advised to contact the primary supervisor. How to Apply.

The programme page lists a closing date of 8 January 2027; detailed application instructions specify 11:45 p.m. UK time. The page does not spell out GMT/UTC. Interviews are planned for the end of March 2027, with the studentship starting in October 2027. Confirm that the online portal uses the same closing time and ask which time zone its deadline display follows. How to Apply, programme dates.

Applicant Fit and Preparation

Required Background and Skills

The programme’s formal academic criterion is a first- or upper-second-class UK honours degree, or an equivalent qualification gained outside the UK, in an appropriate area of science or technology. The project page does not specify a particular degree title, grade above this threshold, English test score or prior PROTAC experience. English certification is requested where applicable; the required score and accepted alternatives are not stated on the project-specific pages. Eligibility, How to Apply.

Preferred Experience and Suggested Preparation

The application form explicitly asks applicants to describe laboratory techniques and research projects they have undertaken, and the personal statement is limited to one A4 page. That is an application-evidence request, not a separate formal eligibility threshold. The advertised tasks suggest that useful preparation may include organic or medicinal chemistry, chemical biology, biochemistry, protein–protein interactions, molecular/cellular physiology, cardiac calcium handling, and quantitative assay design. A competitive statement could show a concrete contribution to a lab project, a technique learned, how controls and reproducibility were handled, and how the applicant would bridge chemistry and biology. These are analyst suggestions; the project does not state that one applicant must already master every stage from synthesis to cardiac-cell assays.

Applicants mainly seeking clinical research, patient contact, computational-only work or in-vivo physiology may find the publicly described chemistry-to-cell-assay focus less aligned with their goals. That is an interpretation of the advertised tasks, not an exclusion criterion. Ask how the work is divided between the two labs and whether cell-based or animal work is planned beyond the stated cellular assays.

Career and Field Market

The project explicitly frames its training as preparation for pharmaceutical or chemical-biology research. Skills that could transfer include small-molecule design and synthesis, targeted-degradation concepts, molecular target validation, protein and cell assays, calcium-handling interpretation, and collaboration between chemistry and biomedical teams. Potential routes include pharmaceutical/biotechnology discovery research, chemical biology, medicinal chemistry, assay development, pharmacology, and academic translational research; these are plausible fields, not guaranteed destinations.

The UK life-sciences sector is substantial and the government’s 2026 skills assessment projects about 66,000 additional jobs in priority occupations between 2025 and 2035, alongside replacement demand, while identifying elevated recruitment pressure across many priority roles. The ABPI’s 2026 pharmaceutical investment report estimates the sector could create up to 81,300 new jobs by 2035 if growth accelerates and notes that roughly 80% of UK pharmaceutical job postings require a degree or higher. These are broad sector projections, not forecasts of heart-failure drug-discovery openings or of a PhD graduate’s employment. The most relevant project-specific market signal is the stated pharmaceutical/chemical-biology training aim, not a guarantee of industry entry. Skills England, Life Sciences sector assessment 2026, ABPI pharmaceutical investment report 2026.

Next Actions and Questions to Verify

Before Applying

• Ask the programme to confirm whether the full 2027/28 international research fee of £33,708 is covered for every funded year, whether any student liability or bench fee can remain, and whether the award includes laboratory costs beyond tuition.
• Confirm the 2027/28 stipend, and reconcile the live programme figure of £21,805 with the eligibility page’s older £20,780 figure.
• Confirm the portal’s deadline time zone and exact closing time, and check whether the interview is expected in person or online.
• Ask the primary supervisor what the 2024 Glasgow thesis established, what is genuinely new in this project, and which starting compounds/data may be discussed.
• Confirm the required English-language score and any country-specific academic equivalence before preparing the application.
• Complete the one-page statement with concise examples of relevant lab techniques, research work, project motivation and why this cross-disciplinary training route fits the applicant’s goals.

At Interview

• What PLN-binding ligand and E3 ligase will the project test, and what chemistry or preliminary data already exist?
• How will the team distinguish PLN degradation from simple inhibition or disruption of the PLN–SERCA interaction? Which target-engagement, degradation, selectivity and rescue controls are planned?
• Which cell models and endpoints are core: protein abundance, SERCA activity, calcium cycling, contractility, electrical/arrhythmia measures, or something else?
• What is the planned progression from molecular and cellular proof of concept, and are animal studies in or out of scope?
• How will the team address cell-type specificity, E3-ligase availability, potential compensation by other calcium-handling proteins and the risk of excessive calcium signaling?
• Which lab hosts compound design, synthesis and cell assays, and what facilities, training and supervisor meeting structure are committed?

Before Accepting an Offer

• Obtain written confirmation of the degree-awarding institution, registering school, formal registration/write-up period and assessment route.
• Confirm the funded duration, each-year stipend, full international tuition coverage, lab-cost/bench-fee treatment and any other exclusions.
• Request an itemized estimate of visa and IHS costs; budget for travel, housing deposit, arrival costs and the possibility that actual Glasgow living costs exceed the University’s broad monthly range.
• Clarify the scope of the research beyond the public summary, the status of prior work and any limits on sharing or publishing results.

Evidence and Sources

Project, Programme, Funding and Application

• Official project page
• MVLS/EPSRC doctoral training programme
• How to Apply
• Eligibility and funding notes
• Glasgow postgraduate research fees 2027/28
• UKRI stipend and fee guidance
• Student visa fees
• Immigration Health Surcharge rates
• Glasgow international-student FAQ and living-cost estimate

School, Programme and Training Context

• Glasgow 2026 subject-ranking summary
• REF 2021 Clinical Medicine environment statement
• MVLS Graduate School
• MVLS PGR registration and Graduate Skills Pathway
• University of Glasgow postgraduate research regulations

Supervisors, Team and Related Research

• Will Fuller profile
• David France profile
• Related Glasgow PhD thesis record, 2024
• Bai et al., 2024, targeted zDHHC degradation
• Kuo et al., 2025, targeted protein palmitoylation tools
• Luptak et al., 2025, state-selective degraders
• Howie et al., 2024, phospholemman regulation

Scientific Field and Career Context

• Qin et al., 2022, PKA–phospholamban structures
• Cleary et al., 2024, PLN regulation of SERCA
• Kho, 2023, SERCA-targeted heart-failure therapies
• Redel-Traub et al., 2025, calcium regulation and heart failure/arrhythmia
• Tsai et al., 2024, targeted protein degradation mechanisms and clinical landscape
• Skills England, Life Sciences sector skills assessment 2026
• ABPI pharmaceutical investment competitiveness report 2026