Fixed-term

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. Multicellular organisms must organize their morphology and physical characteristics. Amidst changes to cell function and specialization, cells must maintain spatiotemporal regulation of communication. We aim to determine the molecular mechanisms of trafficking during dynamic responses to cell changes and specialization. We focus on polarized trafficking, a pathway responsible for intracellular and extracellular communication. These pathways and their components are fundamental, yet despite this importance, we do not understand the mechanisms enabling functional plasticity. The essential and central machinery for polarized trafficking is the exocyst complex. This protein complex and its associated regulatory machinery tethers diverse cargo vesicles to distinct plasma membrane sites. Yet how regulation enables dynamic response amidst change is unclear. We offer projects related to our aims to determine mechanisms for cargo vesicle recognition, reveal a structural ensemble illuminating mechanistic flexibility, and determine the functional mechanism for polarized trafficking-mediated secretion in specialized cells. These projects span stem cell biology to structural biology including cryo-electron microscopy. We harness in vitro reconstitution and structural biology approaches coupled to experimental cell biology in dynamic and complex cell systems. This interdisciplinary approach enables student training in state-of-the-art skills with an expectation to leave the lab as a PhD having mastered two distinct approaches. Together, we will transform our understanding of the role for polarized trafficking in dynamic and specialized cell systems, leading towards a capacity for modulation of communication. 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 David Murray Principal Investigator/Senior Lecturer d.h.murray@dundee.ac.uk +44 (0)1382 381731

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. It is well-established now that during development biochemical parameters as well as mechanical cues are important to generate patterning and morphogenesis. In epithelial tissues for instance, cells can control their shape by subcellular alterations of force production. When such changes are locally coordinated across groups of cells, collective cell shape changes drive morphogenesis. During development the level of tension and stress in tissues can affect the proliferation of cells within, the fate of cells and the shape of organs. Furthermore, cells in certain diseases alter their mechanical properties raising the question of how epithelial tissues control their tension. Central question A defining feature of epithelial cells is that they are polarised. The establishment of apico-basal polarity is driven by protein complexes that are conserved between flies and humans and important for the physiological roles of the epithelium. Our lab recently found that the cell polarity machinery impacts the mechanical properties of epithelial cells corroborating links in the literature suggesting that biochemical cues from the cell polarity machinery and contractility regulation are highly coupled. However, the molecular nature of this regulation is unclear and will be addressed in this project. Approach Non-muscle myosin II (myosin II) is a motor protein that drives contraction of the actin cytoskeleton and generates force. The pathways leading to myosin II activation are well understood, yet the mechanisms that suppress it, less so. In this project the mechanisms repressing myosin II activity in Drosophila will be studied to better understand tension regulation in epithelial cells. Key questions in cell and developmental biology are how these actomyosin behaviours are triggered and what physiological outputs they drive. Actomyosin is further a prime example of an active gel and understanding its properties and behaviours is of central importance in physics of active, out of equilibrium systems. Drosophila has been instrumental in revealing the genes that operate in the pathways that lead to myosin II activation due to its genetic tractability, the possibility to perform quantitative live cell imaging and the generation of transgenic fly lines allowing targeted testing of hypotheses. This type of data naturally lend itself to modelling and biophysical analysis. Nature of project and training opportunities In this interdisciplinary project at the interface of cell biology, developmental biology and biomechanics you will use genetics, chemical genetics and opto-chemical genetics, state of the art laser scanning confocal microscopy and image analysis and biophysical approaches to study how cell polarity regulates mechanical parameters of epithelia in the fly. The study will explore upstream regulatory mechanisms linking actomyosin regulation to cell mechanics and polarity, offering insights into feedback and regulation. The methods applied in this project are highly transferable, therefore training on this project will enable you to proceed a career in academia as well as industry. 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 Jens Januschke Professor j.januschke@dundee.ac.uk +44 (0)1382 386169 Second supervisor Person Professor Rastko Sknepnek Professor r.sknepnek@dundee.ac.uk +44 (0)1382 385699

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. Parkinson’s disease (PD) is a movement disorder that is now the fastest growing neurological disorder in the world. Despite much research the disease is incurable and there are no treatments that can slow the disease down. The discovery of genetic mutations in rare familial forms has transformed our understanding of the origins of PD but the function of these genes is poorly understood. Mutations in PTEN-induced kinase 1 (PINK1) cause autosomal recessive PD. PINK1 is unique amongst all protein kinases due to the presence of a mitochondrial targeting domain that localises it to mitochondria. Our lab has made a number of groundbreaking discoveries and uncovered mechanisms that explain how PINK1 and Parkin activation lead to the removal of damaged mitochondria by mitophagy. Recent work identified the mechanism by which PINK1 is activated at the mitochondrial TOM complex (Raimi, Ojha et al., Science Advances 2024). Excitingly based on this research there are now Phase I trials for PD patients using molecules that boost PINK1-dependent mitophagy. However, there remain many outstanding questions on the regulation of PINK1 and its downstream biology that may lead to new diagnostic and therapeutic strategies to tackle PD. These include the molecular mechanism by which PINK1 senses mitochondrial damage; the role of other PINK1 substrates including Rab GTPases; how PINK1 mutations impacts other organelles including lysosomes and endosomes; the roles of the PINK1 pathway in the brain; and identification of regulators and PINK1-independent mechanisms that may compensate for loss of PINK1 in cells. Our lab uses a multidisciplinary approach to address these questions and the successful student will gain exposure and training in many state-of-the-art methods including mass spectrometry / proteomic technologies; CRISPR/Cas9 technologies; cutting edge methods to isolate organelles, and tissue culture using human iPSC-derived neurons or mice-based analysis. The lab also collaborates with many labs around the world and is actively involved in public engagement. In addition to training and development opportunities within the  MRC Protein Phosphorylation & Ubiquitylation Unit and Dundee , the Muqit lab is a member of the EMBO Young Investigator Network (https://people.embo.org/profile/miratul-muqit) and students have opportunities to attend EMBO PhD courses and workshops. The lab is also part of the innovative global Aligning Science Across Parkinson’s (ASAP) initiative that also enables students to experience cutting edge development opportunities. 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. Meet Miratul and find out more about his research 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 Miratul Muqit Professor M.Muqit@dundee.ac.uk +44 (0)1382 388377 Second supervisor Person Professor Dario Alessi Science Director, Professor of Signal Transduction d.r.alessi@dundee.ac.uk +44 (0)1382 388058

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. Bacteria sense and respond to their environment via intricate networks of signalling systems. Two-component signalling (TCS) systems comprise a sensor kinase that detects environmental signals and a response regulator that alters gene expression to promote adaptive phenotypic change. This ability to detect and respond to a fluctuating environment underpins adaptive antimicrobial resistance, whereby the susceptibility of a microbe to antibiotics changes as a function of its environment. Pseudomonas aeruginosa encodes for around 60 TCS systems, affording it phenotypic plasticity that contributes to its success as an opportunistic pathogen in different host tissues. Drug tolerance and resistance in P. aeruginosa is a major barrier to treatment, especially in chronic infection. This PhD would investigate the contribution of TCS to P. aeruginosa antimicrobial tolerance in different infection contexts. The student will address fundamental questions in infection biology, including: Which TCS systems underpin drug tolerance or resistance in different infection environments. What are the environmental triggers for TCS-mediated resistance. How does TCS-induced microbial physiology determine resistance. The student will generate P. aeruginosa fluorescent reporter and gene deletion strains for individual TCS genes and will use these in phenotypic screens with an antibiotic panel that includes agents with different modes of action. Screening will be undertaken in environments reflective of various infection contexts. After determining which TCS systems are active in which environments and which contribute to tolerance to each drug class, the student will profile the testing environments to determine the physical or chemical cues for TCS signalling and will characterise bacterial physiology to determine the mechanisms of drug resistance. Training will be provided in laboratory microbiology and molecular biology. The student will have the opportunity to learn skills in high-throughput compound screening, advanced microscopy and flow cytometry techniques, mutagenesis, phenotypic assays and big data approaches including RNA-seq and proteomics. The project will benefit from the expertise and facilities of the Drug Discovery Unit. Ongoing collaborations with industry on antimicrobial drug development projects offer opportunities for the student to broaden their professional network and to share their findings with key stakeholders. The PhD offers an opportunity to address a major global health challenge, by contributing to the fight against accelerating antimicrobial resistance. Improved understanding of how TCS systems contribute to phenotypic resistance may uncover new avenues for therapy or help us to make informed choices of which drug to use in which infection contexts. 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 Daniel Neill Senior Lecturer dneill001@dundee.ac.uk +44 (0)1382 388899 Second supervisor Person Dr Megan Bergkessel Principal Investigator mbergkessel001@dundee.ac.uk +44 (0)1382 386464

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. The need to distinguish self from non-self is a requirement spanning the kingdoms from bacteria to plants and humans. Many microbes are highly clonal and frequently restrict cooperative behaviours to their clonal isogenic counterparts (kin). This behaviour means that sophisticated systems of detecting kin and/or responding to non-kin have evolved. As intraspecies competition is a driver of evolutionary change, and a fundamental force that influences community structure during infection and commensal situations, understanding the mechanisms of intraspecies competition is essential to our future ability to engineer and control microbial communities across a myriad of applications. Bacillus subtilis is ubiquitous in the environment and plays many important industrial roles, including the production of enzymes, such as amylases and proteases. Furthermore, it has become widely applied as a live biological agent in i) microbial cleaning products, ii) probiotics used to promote animal and human health, and iii) biofertilizers and biopesticides used in agriculture. These applications make B. subtilis a pioneering example of efforts to functionally manipulate existing microbial communities. When Bacillus sp. are deployed as live biological agents, the spores contained in the product need to germinate and survive encounters with diverse microbes already in the receiving environment. These microbes will invariably include different B. subtilis strains given its ubiquitous nature. Competition between the existing and introduced strains of the same species is important in determining the success of occupying a niche. Therefore, understanding the mechanisms of intraspecies competition is critical to ensuring the efficacy of live microbial products. Given that we are only starting to catalogue B. subtilis strain diversity, there are large gaps in our understanding of how genomic differences drive competitive dynamics during intraspecies interactions. This PhD will explore this topic and will allow the student to develop skills in molecular microbiology, imaging and other scientific processes as directed by the needs of the experiments. In addition to developing your technical scientific skills and associated data analysis strategies, you will have the chance to develop communication skills through presentations and events engaging with members of the public. You could use the opportunity to develop project management skills and line management through the co-supervision of undergraduate students. 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 Nicola Stanley-Wall Deputy Vice-Principal (Life Sciences) N.R.Stanleywall@dundee.ac.uk +44 (0)1382 386335 Second supervisor Person Professor Sarah Coulthurst Professor and Wellcome Trust Senior Research Fellow S.J.Coulthurst@dundee.ac.uk +44 (0)1382 386208

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. Many species of bacteria use a contractile nanomachine known as the Type VI secretion system (T6SS) to deliver a wide range of toxic proteins, known as ‘effectors’, directly into neighbouring cells. The T6SS plays a key role in the virulence and competitiveness of diverse Gram-negative bacteria, including important human, animal and plant pathogens. In some cases the T6SS can be used to directly attack host cells, as a classical virulence factor. However the primary role of the T6SS is believed to be during inter-bacterial competition, when bacteria use the T6SS to deliver anti-bacterial effectors into other bacterial cells, efficiently killing or disabling competitors. Additionally, we have recently discovered that bacteria can also use T6SS-delivered effectors against microbial fungi, including important fungal pathogens. Anti-microbial T6SSs thus provide a competitive mechanism to allow pathogens to proliferate in polymicrobial infection sites or environmental reservoirs and ultimately cause disease. Understanding T6SS-mediated effector delivery and the lethal consequences of these effectors on targeted cells therefore offers the potential to uncover new ways to kill or inhibit bacterial and fungal pathogens, as well as fundamental insights into the dynamics of polymicrobial communities more broadly. In the Coulthurst group, we study the roles and regulation of the T6SS, the mechanisms of effector delivery, the nature and mode-of-action of T6SS-dependent effector proteins, and the distribution and evolution of effectors and self-protecting immunity proteins. We utilise a wide range of molecular, cellular, genetic, genomic and structural biology approaches and focus on representative examples of Gram-negative bacterial pathogens. The PhD project on offer will fall within this area and the specific project undertaken will be developed around an exciting current question or line of research in the group and the interests of the student. The student will gain a experience in a variety of molecular, cellular, structural, ‘omics’ and/or bioinformatics approaches as appropriate, in addition to a strong grounding in molecular microbiology. We work with a broad set of collaborators who can provide further access to cutting-edge imaging, analytical and computational approaches. The student will also have varied opportunities to engage with the international research community and the general public. 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 Sarah Coulthurst Professor and Wellcome Trust Senior Research Fellow S.J.Coulthurst@dundee.ac.uk +44 (0)1382 386208 Second supervisor Person Professor Nicola Stanley-Wall Deputy Vice-Principal (Life Sciences) N.R.Stanleywall@dundee.ac.uk +44 (0)1382 386335

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. Ubiquitination is a fundamental post-translational modification (PTM) crucial for a wide range of cellular processes, including protein degradation, localization, quality control, DNA repair, cell signaling, and immune responses. Traditionally, ubiquitin attaches to lysine residues via isopeptide bonds. However, recent advances have uncovered a novel form of ubiquitination – non-canonical ubiquitination – where ubiquitin binds to serine, threonine, and other hydroxyl-containing biomolecules through ester bonds. This dynamic and less stable modification challenges established paradigms and opens up new possibilities for interactions with other PTMs, such as phosphorylation and glycosylation. Investigating non-canonical ubiquitination promises to deepen our understanding of cellular mechanisms and identify new therapeutic targets for diseases linked to dysfunctional ubiquitination. The De Cesare Lab has identified several non-canonical ubiquitin conjugating enzymes (E2s) – UBE2Q1, UBE2Q2, and UBE2QL1 – that mediate ubiquitin attachment to non-lysine residues. Notably, UBE2Q1 knockout mice exhibit infertility due to defective embryo implantation, highlighting the critical role of these non-canonical E2s in early developmental processes and reproductive biology. Additionally, altered expression of UBE2Qs has been observed in various human cancers, raising important questions about their roles in human health and disease. Research Questions This PhD project will address the following key questions: Roles of Non-Canonical Ubiquitination: How does non-canonical ubiquitination affect cellular processes and human health, including links to infertility and cancer? Biological Functions of Non-Canonical E2s: What are the substrates and functional roles of non-canonical E2s (UBE2Q1, UBE2Q2, UBE2QL1) in different cellular contexts? Interactions with Other PTMs: How does non-canonical ubiquitination interact with and regulate other PTMs such as phosphorylation and glycosylation? Methodology and Training Opportunities This project offers flexibility to align with the student’s specific interests and incorporates a range of advanced methodologies: Mass Spectrometry: Use MALDI-TOF and LC/MS to identify and analyze substrates of non-canonical E2s, providing detailed insights into their interactions and modifications. Protein Biochemistry: Employ cutting-edge techniques to study protein interactions, modifications, and functional properties of non-canonical E2s and their substrates. Structural Biology: Utilize X-ray crystallography and cryo-electron microscopy to reveal the structural details of non-canonical E2-substrate interactions. Molecular Biology: Perform gene editing, expression analysis, and functional assays to elucidate the roles of non-canonical E2s and their substrates. Cell Biology: Conduct cellular assays to evaluate the impact of non-canonical ubiquitination on cellular functions and disease models. This comprehensive training will provide the student with valuable skills across multiple disciplines, preparing them for successful careers in both academic and industrial settings. Application To apply or for more information about this PhD position, please contact Dr. Virginia De Cesare at vdecesare@dundee.ac.uk. Join us to explore the innovative field of non-canonical ubiquitination and contribute to pioneering research. 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. Meet Virginia and hear more about her research 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 TypePerson Dr Virginia De Cesare Principal Investigator v.decesare@dundee.ac.uk +44 (0)1382 386296 Second supervisor TypePerson Professor Ronald Hay Professor R.T.Hay@dundee.ac.uk +44 (0)1382 386309