Fixed-term
Effect of vaginal microbiota on human sperm function
Funding – self-funded/externally sponsored applicants (PhD Fees can be found here) Applications are accepted year round Standard Entry dates – January and September Applicants are expected to have a degree (equivalent of Honours or Masters) in a relevant discipline. Infertility is linked to dysbiosis in female reproductive tract but individual microbes responsible for infertility have not been established. In a pilot study, we collected vaginal swab from several women and isolated 15 unique microbial taxa. Two microbial taxa were isolated from multiple women. We found that conditioned media from one of these bacteria affected total and hyperactivated sperm motility on purified spermatozoa from human males. We hypothesize that secreted or volatile factors from FRT microbiota affects (i) sperm motility, (i) sperm viability, or (ii) sperm hyperactivation. This PhD project will involve the identification of soluble and volatile molecules from FRT microbiota by liquid chromatography and gas chromatography mass spectrometry respectively. Subsequently, the PhD student will study sperm viability, total motility, hyperactive motility as well as ability to penetrate through cervical mucous analogue (in Kraemer assay). This study will be conducted in collaboration with investigators at the Reproductive Medicine Research Group (RMRG) at University of Dundee. Impact: The outcome of this focussed study will help identify specific factors affecting sperm function. Variants of such molecule could be new generation of non-hormonal contraceptives. This would be developed in future in collaboration with Drug Discovery Unit at University of Dundee. The student will acquire training in microbiology, LC-MS, GC-MS, microscopy and various sperm motility and hyperactivation assays. The student will receive training in scientific writing, statistics and data management. The student will also receive mentoring support in an inclusive environment. How to apply Please contact the principal project supervisor to discuss your interest further, see supervisor details below. For general enquiries, contact SLS-PhDAdmin@dundee.ac.uk Supervisors Principal supervisor Person Dr Varsha Singh Senior Lecturer and Royal Society Wolfson Fellow vsingh001@dundee.ac.uk +44 (0)1382 388898
The regulation of protein synthesis and turnover in the adaptive immune system
Funding – self-funded/externally sponsored applicants (PhD Fees can be found here) Applications are accepted year round Standard Entry dates – January and September Applicants are expected to have a degree (equivalent of Honours or Masters) in a relevant discipline. This project aims to understand how B lymphocytes, key cells of the adaptive immune system, regulate protein synthesis and turnover. B lymphocytes (B cells) produce antibodies which bind to pathogens such as viruses and bacteria and target them for destruction. Short-lived and long-lived antibody producing B cells provide rapid and durable protection against infection and B cells play a vital role in providing an effective vaccine response. B cell dysfunction is linked to a range of diseases and there is intense interest in understanding the core activities of B cells and how these are impacted in disease settings and in response to ageing. B cells are protein production factories, with each cell capable of producing up to 10,000 antibodies every second. This is equivalent to the cell producing its own mass in antibodies every day. Given the scale of antibody production, protein synthesis and turnover (proteostasis) must be tightly regulated to maintain health. In this project we want to understand how B cells maintain proteostasis during their activation and differentiation into antibody producing effector populations. Critical knowledge gaps exist in our understanding of the proteostasis machinery used by B cells and how this is impacted under conditions of cellular stress including nutrient stress. Using high-sensitivity quantitative proteomics we will map the core machinery for protein degradation, including components of the ubiquitin-proteasome system, and elucidate the impact of modulating this machinery on cell phenotypes. This project will provide novel mechanistic insights into how B cells regulate protein turnover, which is valuable for translating into ageing and disease settings in the future and may lead to novel strategies for modulating B cell activities. This project will also provide the ideal opportunity for a PhD student to master a range of molecular and cell biology skills at the forefront of the field including biochemistry, quantitative proteomics, big data, targeted gene editing and immune phenotyping. How to apply Please contact the principal project supervisor to discuss your interest further, see supervisor details below. For general enquiries, contact SLS-PhDAdmin@dundee.ac.uk Supervisors Principal supervisor Person Dr Andy Howden Principal Investigator/Lecturer a.howden@dundee.ac.uk +44 (0)1382 385767 Second supervisor Person Professor Doreen Cantrell Wellcome Trust Principal Research Fellow d.a.cantrell@dundee.ac.uk +44 (0)1382 385156
Structural Chemical Biology of Molecular Glue Degraders Mode of Action
Funding – self-funded/externally sponsored applicants (PhD Fees can be found here) Applications are accepted year round Standard Entry dates – January and September Applicants are expected to have a degree (equivalent of Honours or Masters) in a relevant discipline. This PhD project will define how novel molecular glue degraders (MGDs) hijack and reprogram E3 ligases to trigger selective protein ubiquitination and proteasomal degradation. The student will combine structural, biophysical, chemical biology and proteomic approaches to reveal atomic and mechanistic rules that govern glue-mediated engagement, selectivity and downstream fate — and to apply those rules to design tuneable, higher‑performance degraders with translational potential. Why this is exciting? Targeted Protein Degradation (TPD) is a rapidly transformative therapeutic modality with major academic and industrial investment (Nat. Rev. Cancer. 2025). Molecular glues — monovalent degraders that stabilise or create protein–protein interfaces — offer routes to drug previously intractable targets. Recent work from the Ciulli Lab has uncovered unconventional glue mechanisms – e.g. intramolecular bivalent glues (Nature 2024), and covalent recruitment of novel E3s, including dual E3 engagement (bioRxiv 2025) that challenge canonical models and open new opportunities for rational design. This project sits at the interface of basic mechanism and translational chemical biology and promises high‑impact mechanistic insight and tool compounds. Key research questions What are the structural architectures and conformational changes induced by MGDs when engaging targets and E3 ligases? How do binding thermodynamics/kinetics, intrinsic low‑affinity pre‑existing E3:substrate interactions, and cellular context determine selectivity, ubiquitination sites and degradation outcomes? Can structure–mechanism principles be used to rationally tune E3 dependency, potency and resistance profiles (e.g., dual‑E3 or ligase‑switchable degraders; intramolecular bridging, covalent recruitment)? Approaches and objectives Structural biology: determine cryo‑EM and X‑ray structures of binary and ternary assemblies of MGDs; use solution NMR to probe dynamics and disordered regions. Biophysics: map affinities, kinetics, cooperativity and allostery (SPR, ITC, single‑molecule and ensemble assays) to define thermodynamic/kinetic landscapes. Chemical biology & medicinal chemistry: design and test analogue series and “degradation‑tail” variants to dissect chemical determinants of ligase preference and potency. Cellular & proteomic interrogation: use engineered cell lines, ubiquitinomics and quantitative MS‑based interactomics to identify target/neo‑interaction sites, ubiquitination patterns, off‑targets and degradation dependencies. Functional tuning: exploit chemical perturbations to fine-tune E3 engagement and target/isoform selectivity. Training and environment The student will be based in the Ciulli lab at the Centre for Targeted Protein Degradation (CeTPD, https://www.dundee.ac.uk/cetpd). The project can be tailored to the student specific interests and motivations, allowing the student to gain hands‑on training across structural biology (cryo‑EM, crystallography, NMR), biophysics, medicinal chemistry/compound design, chemical biology, CRISPR cell engineering and state‑of‑the‑art MS proteomics. The project is co‑supervised by Professor Ronald Hay, leveraging deep expertise in ubiquitin biology and proteostasis. The Ciulli and Hay laboratories have longstanding collaboration and track-record of co-supervising PhD students leading to high-impact publications (Sci. Adv. 2024). The project will also benefit from access to broad Faculty resources (Drug Discovery Unit, FingerPrint Proteomics Facility) and industry collaborations (e.g., Amphista, Boehringer Ingelheim). Impact This project will deliver mechanistic models and validated chemical tools that define how MGDs operate, establish actionable structure–mechanism guidelines for glue design (including tuneable dual‑E3 strategies), and generate datasets and compounds suitable for high‑impact publications and downstream drug discovery. References (as cited in text) Hinterndorfer, M., Spiteri, V.A., Ciulli, A., Winter, G.E. Targeted protein degradation for cancer therapy. Nat. Rev. Cancer. 2025 Jul; 25(7):493-516. Hsia, O., Hinterndorfer, M., Cowan, A.D., Iso, K., Ishida, T., Sundaramoorthy, R., Nakasone, M.A., Imrichova, H., Schätz, C., Rukavina, A., Husnjak, K., Wegner, M., Correa‑Sáez, A., Craigon, C., Casement, R., Maniaci, C., Testa, A., Kaulich, M., Dikic, I., Winter, G.E., Ciulli, A. Targeted protein degradation via intramolecular bivalent glues. Nature 2024 Mar;627(8002):204-211. Spiteri, V.A., Segal, D., Correa‑Sáez, A., Iso, K., Casement, R., Muñoz i Ordoño, M., Nakasone, M.A., Sathe, G., Schätz, C., Peters, H.E., Doward, M., Kainacher, L., Cowan, A.D., Ciulli, A., Winter, G.E. Dual E3 ligase recruitment by monovalent degraders enables redundant and tuneable degradation of SMARCA2/4. bioRxiv 2025.08.04.668513; doi: https://doi.org/10.1101/2025.08.04.668513 Crowe, C., Nakasone, M.A., Chandler, S., Craigon, C., Sathe, G., Tatham, M.H., Makukhin, N., Hay, R.T., Ciulli, A. Mechanism of degrader-targeted protein ubiquitinability. Sci Adv. 2024 Oct 11;10(41):eado6492. Our research community thrives on the diversity of students and staff which helps to make the University of Dundee a UK university of choice for postgraduate research. We welcome applications from all talented individuals and are committed to widening access to those who have the ability and potential to benefit from higher education. How to apply Please contact the principal project supervisor to discuss your interest further, see supervisor details below. For general enquiries, contact SLS-PhDAdmin@dundee.ac.uk Supervisors Principal supervisor Person Professor Alessio Ciulli Professor, Director of the Centre for Targeted Protein Degradation a.ciulli@dundee.ac.uk +44 (0)1382 386230 Second supervisor Person Professor Ronald Hay Professor R.T.Hay@dundee.ac.uk +44 (0)1382 386309
Heat shapes plant growth – unravelling crosstalk between temperature and hormone signalling pathways in the control of leaf development
Funding – self-funded/externally sponsored applicants (PhD Fees can be found here) Applications are accepted year round Standard Entry dates – January and September Applicants are expected to have a degree (equivalent of Honours or Masters) in a relevant discipline. Ambient temperature has profound effects on almost all aspects of plant development, from the onset of seed germination and seedling establishment to flower and fruit production, and thereby also impacts crop quality and yield. With the progression of climate change, plants in temperate regions are challenged by more frequent heat waves as well as an overall rise in ambient temperature. Elucidating the mechanisms by which plants sense and respond to elevated temperatures is vital to fully understand how climate change will affect plant growth in the future and may also indicate ways to mitigate negative effects of rising temperatures on crop production. In the model plant Arabidopsis thaliana, elongation of roots, stems and petioles are among the best understood responses to high temperature. A signalling network has been identified that controls these processes by modulating the production, distribution and sensing of several plant hormones, auxin and brassinosteroids in particular (1). High temperatures also trigger morphological changes in the leaf, but here, the roles of phytohormones are less well understood. In this project, you will employ genetic, pharmacological and molecular biology approaches to elucidate the role of several phytohormones in the temperature-dependent control of leaf morphology in Arabidopsis. You will analyse phenotypic changes in leaf morphology caused by perturbations in hormone level and perception at different temperatures. You will monitor alterations in hormone distribution and signalling by confocal microscopy, using the newest generation of hormone reporters and biosensors (2). You will link these to changes in gene expression and thereby establish a causal relationship between temperature signals, hormonal cascades and alterations in plant development. This project will train you in a wide range of technical skills including fundamental genetics and molecular biology as well as advanced confocal microscopy. Through the project you will gain an in-depth understanding of experimental design, quality control and statistical analysis of results, but also develop critical thinking and scientific scrutiny. You will have the opportunity to communicate your findings in departmental seminars and at scientific conferences, to participate in outreach activities and to substantially contribute to publishing your research. At the end of the PhD, these technical and transferrable skills will leave you excellently positioned to pursue a career in academia, industry, or another science-related field. You will be supervised by Dr Martin Balcerowicz (MBalcerowicz001@dundee.ac.uk), a Royal Society University Research Fellow with extensive expertise in plant temperature signalling (3). You will be based at the James Hutton Institute, a diverse and collaborative research environment that hosts the University of Dundee’s Plant Science Department and is the site of several exciting research developments, including the Advanced Plant Growth Centre (APGC), the International Barley Hub (IBH), a Molecular Phenotyping Centre and a super-resolution imaging platform. References: (1) Lu et al., 2021, Stress Biology 10.1007/s44154-021-00022-1 (2) Balcerowicz et al., 2021, Plant Physiol. 10.1093/plphys/kiab278 (3) Chung, Balcerowicz et al., 2020, Nat. Plants 10.1038/s41477-020-0633-3 Our research community thrives on the diversity of students and staff which helps to make the University of Dundee a UK university of choice for postgraduate research. We welcome applications from all talented individuals and are committed to widening access to those who have the ability and potential to benefit from higher education. How to apply Please contact the principal project supervisor to discuss your interest further, see supervisor details below. For general enquiries, contact SLS-PhDAdmin@dundee.ac.uk Supervisors Principal supervisor Person Dr Martin Balcerowicz Principal Investigator mbalcerowicz001@dundee.ac.uk Second supervisor Person Dr Sarah McKim Reader s.mckim@dundee.ac.uk +44 (0)1382 385398
Regulation of microglial phenotypes by adenosine and in contribution to ageing in the brain
Funding – self-funded/externally sponsored applicants e.g. (PhD Fees can be found here) Applications are accepted year round Standard Entry dates – January and September Applicants are expected to have a degree (equivalent of Honours or Masters) in a relevant discipline. Microglia are the major innate immune cells in the central nervous system and are responsible for responding to invading pathogens, removal of damaged or apoptotic cells and contributing to neuronal development via synaptic pruning. To achieve this, microglia must be able to adopt a spectrum of inflammatory and anti-inflammatory phenotypes. The balance between the phenotypes is affected by aging, with microglia from older individuals displaying a greater propensity for an activated phenotype. This in turn may promote age-related pathologies in the CNS. The factors which control the polarisation of microglial phenotypes are however not well understood. This project will seek to understand the factors controlling microglial polarisation and how these impact on processes in healthy aging and neurodegeneration. In innate immunity, macrophages play a similar role in peripheral tissues to microglia in the CNS. Anti-inflammatory phenotypes in macrophages can be regulated by the SIK kinase family, which are in turn regulated downstream of G protein coupled receptors that activate cAMP signalling, such as the prostaglandin E2 (PGE2) receptors EP2 and 4. Multiple isoforms of the PGE2 receptor exist and the effects of PGE2 are dependent on the receptor isoform expressed by the cell; EP2 and EP4 activate cAMP signalling while EP3 inhibits due to differential use of Galpha subunits. In the proposed project we will examine the role that the SIK pathway plays in regulating microglial function downstream of PGE2, which has immunomodulatory effects in the CNS, and adenosine, which has roles in both neurotransmission and immunomodulation as well as potential links to ageing. Similar to PGE2, adenosine acts via receptors that are in the GPCR family, and like PGE2 receptors different adenosine receptor isoforms have differential effects on cAMP signalling. To address which receptor isoform is critical, synthetic agonists or antagonists for specific PGE2 or adenosine receptor isoforms will be used, and differences in isoform expression and utilization in microglia from young and aged mice will be examined. High resolution proteomics using sate of the art mass spectrometry will be used to examine the effects of PGE2 and adenosine on proteome remodelling in microglia, and this will be linked to functional assays to determine the inflammatory phenotype of the cells. Finally to extend the studies into humans, human iPS cell derived microglia will be analysed. Together these approaches will enhance our understanding of how microglial function is controlled during ageing. The PhD will provide training in a range of techniques including mass spectrometry, bioinformatics and stem cell culture. Our research community thrives on the diversity of students and staff which helps to make the University of Dundee a UK university of choice for postgraduate research. We welcome applications from all talented individuals and are committed to widening access to those who have the ability and potential to benefit from higher education. How to apply Please contact the principal project supervisor to discuss your interest further, see supervisor details below. For general enquiries, contact SLS-PhDAdmin@dundee.ac.uk Supervisors Principal supervisor Person Professor Simon Arthur Professor j.s.c.arthur@dundee.ac.uk +44 (0)1382 384003 Second supervisor Person Dr Amy Lloyd Race Against Dementia – Alzheimer’s Research UK Fellow alloyd001@dundee.ac.uk
Cellular landscapes of protein secretion
Funding – self-funded/externally sponsored applicants (PhD Fees can be found here) Applications are accepted year round Standard Entry dates – January and September Applicants are expected to have a degree (equivalent of Honours or Masters) in a relevant discipline. Approximately one-third of the human genome encodes membrane and secretory proteins that must be delivered to the correct sub-cellular or extracellular compartment. The first step in protein delivery via the secretory pathway is capture into COPII vesicles that transfer proteins from their site of synthesis in the endoplasmic reticulum (ER) to the Golgi. Our detailed understanding of COPII vesicle formation has been largely based on characterizing this process in model cell types using a small number of well-characterized cargo proteins. This project aims to understand the mechanisms of secretion in diverse cell types with distinct physiology. In this way, we hope to develop insight into the diversity of protein secretion and develop small molecules that will selectively inhibit subsets of protein secretion events. This project will leverage expertise in the human pluripotent stem cell facility with proteomic analysis of protein secretion to reveal specific pathways that yield the unique secretion fingerprint of a given cell type. Starting with CRISPR-based genome editing of pluripotent stem cells, we will first introduce mutations in well-characterized COPII proteins and ER export receptors. Next, we will differentiate these cells into different cell types, including hepatocytes, gut epithelia and neurons, and monitor the secreted proteome using mass spectrometry. Working with the Drug Discovery Unit, we will engineer small molecules that inhibit specific protein-protein interactions that drive specific secretion events and thus target physiologically important secreted proteins for therapeutic intervention. Our research community thrives on the diversity of students and staff which helps to make the University of Dundee a UK university of choice for postgraduate research. We welcome applications from all talented individuals and are committed to widening access to those who have the ability and potential to benefit from higher education. How to apply Please contact the principal project supervisor to discuss your interest further, see supervisor details below. For general enquiries, contact SLS-PhDAdmin@dundee.ac.uk Supervisors Principal supervisor Person Professor Liz Miller Professor emiller003@dundee.ac.uk +44 (0)1382 388913
Mechanism of action of the tumour suppressor ARID1A
Funding – self-funded/externally sponsored applicants (PhD Fees can be found here) Applications are accepted year round Standard Entry dates – January and September Applicants are expected to have a degree (equivalent of Honours or Masters) in a relevant discipline. Human BAF complexes are a series of multi-subunit assemblies that act to reconfigure chromatin. They are conserved across eukaryotes and were first identified in yeast where they were named SWI/SNF complexes and found to act to enable gene expression by regulating chromatin accessibility. In mammals, the predominant BAF complex acts mainly at enhancers where it generates accessible chromatin. The ARID1A subunit of this complex is mutated in approximately 50% of endometrial and ovarian clear cell cancers, but at background levels in tumours of other tissues such as Glioblastoma. Despite these prominent associations, the mechanistic basis for this tissue specificity is poorly understood. To gain insight into the mechanisms by which ARID1A reprogrammes cells, we have engineered cell lines to allow acute degradation of ARID1A. This enables us to track epigenetic and transcriptional changes over time. In this project we aim to reveal the pathway(s) by which loss of ARID1A promotes cancer. In this project changes to the distribution of transcription factors, histone modifications and changes to chromatin structures will be monitored to characterise the rapid changes driven by loss of ARID1A. This will involve the use of techniques such as chromatin immunoprecipitation ATAC-seq and nuc-seq. We will also monitor transcription using single cell RNA seq. We will integrate this data to discover gene regulatory networks triggered by loss of ARID1A. We will perform these experiments in cells of different tissue types to gain insight into why action of BAF complexes is tissue specific. This project will provide a deeper understanding into how ARID1A affects chromatin structure and transcription in different tissues. Our research community thrives on the diversity of students and staff which helps to make the University of Dundee a UK university of choice for postgraduate research. We welcome applications from all talented individuals and are committed to widening access to those who have the ability and potential to benefit from higher education. How to apply Please contact the principal project supervisor to discuss your interest further, see supervisor details below. For general enquiries, contact SLS-PhDAdmin@dundee.ac.uk Supervisors Principal supervisor Person Professor Tom Owen-Hughes Professor t.a.owenhughes@dundee.ac.uk +44 (0)1382 385796 Second supervisor Person Dr Gabriele Schweikert Principal Investigator/Senior Lecturer g.schweikert@dundee.ac.uk +44 (0)1382 388895