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. To maintain genetic integrity, human cells must inherit the whole set of chromosomes without any loss or excess when the cell division takes place. To ensure this process, each copy of duplicated chromosomes must segregate to opposite spindle poles during mitosis. This process relies on the correct interaction of chromosomes with the mitotic spindle. Defects in this process lead to numerical chromosomal instability (N-CIN), which is closely associated with chemotherapy resistance and poor prognosis of cancers. The Tanaka group and others have recently discovered a novel perinuclear actomyosin network formed in early mitosis (PANEM). The PANEM rapidly assembles in early mitosis (prophase), shows contraction immediately after the nuclear envelope breakdown (NEBD), and pushes chromosomes inward to facilitate their interaction with the mitotic spindle (Booth et al 2019). The defects in PANEM assembly or contraction lead to a delay in chromosome congression to a metaphase plate and frequent errors in chromosome segregation. Intriguingly, some cancer cells (e.g. HeLa) with N-CIN lack the PANEM. In this project, we will address molecular mechanisms facilitating the rapid PANEM assembly in prophase and identify the trigger of PANEM contraction immediately after NEBD. These dynamic characters of the PANEM are crucial for chromosome positioning in early mitosis to ensure correct chromosome segregation later in mitosis. Moreover, we will address whether the lack of PANEM in cancer cells with N-CIN plays a causative role in N-CIN in these cancer cells. The student, who works on this project, will learn methods of advanced live-cell imaging, AI-driven image analyses, CRISPR gene editing and mass-spectrometry. If you have any questions about this project, please do not hesitate to contact Prof Tomo Tanaka (t.tanaka@dundee.ac.uk). Reference Booth AJR., Yue, Z, Eykelenboom JK, Luxton GWG, Hochegger H & Tanaka TU Contractile actomyosin network on nuclear envelope remnants positions chromosomes for mitosis. eLife 8, e46902 (2019). 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 Tomoyuki Tanaka Professor t.tanaka@dundee.ac.uk +44 (0)1382 385814 Second supervisor Person Dr Tony Ly Principal Investigator/Senior Lecturer t.ly@dundee.ac.uk +44 (0)1382 381627

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. Cell communication requires both a sending and a receiving cell. To send messages, Metazoan harness trafficking machinery. Yet, despite basic knowledge of the components and regulatory factors involved, we lack molecular mechanism. We aim to determine high-resolution structural ensembles of the human exocyst complex. This structure is required to understand functional adaptability, flexibility, and the fundamental biology of cargo delivery to the plasma membrane. This work will have high-level impact to many fields, as nearly all constitutive and specialized cargo secretion uses this machinery. Thus, we are interested in an ambitious and driven student. The student will emerge an expert in protein expression and purification from eukaryotic systems, large protein complex biochemistry, membrane methods, alongside hybrid structural approaches including cryo electron microscopy and tomography. We have collaboration opportunities available with international partners. Please do not hesitate to contact the PI, David Murray, at dhmurray@dundee.ac.uk if interested. 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. Intraepithelial T lymphocytes (IEL) are at the forefront of mucosal immunity – the first immune cells that pathogens encounter in the gut. IEL are central to the protection of the gut against infection and dietary stress, but dysregulated IEL responses are also associated with autoimmune inflammatory bowel diseases such as Coeliac and Crohn’s disease.  These unique T cells reside between nutrient-absorptive intestinal epithelial cells that dictate the fuels available to IEL to allow them to function, but how IEL regulate nutrient absorption and are regulated by the diet is unknown. The aim of this project is to investigate how metabolic adaptation of IEL to the intestinal environment, allows IEL to respond appropriately to intestinal metabolic perturbations, including diet and microbial challenges. We will explore how cellular bioenergetics, macromolecule biosynthesis, and metabolite waste management are regulated in IEL, and how nutrient availability may regulate IEL cross talk with the epithelium. In this project, the student will learn to use state-of-the-art techniques to study metabolism, including metabolomics, mass spectrometry, high-resolution imaging, signalling studies to investigate the pathways regulating IEL metabolic adaptations, and in vivo models with different diets to address how perturbations in these pathways regulate intestinal homeostasis. These studies will provide fundamental insights into how the unique gut-resident immune cells adapt to their environment to maintain the balance between diet, the epithelium and immune responses, findings that can be used to tune IEL activity for treatment of infectious, autoimmune and/or metabolic diseases. Further reading: Brenes AJ*, Vandereyken M*, James OJ, Hukelmann JL, Spinelli L, Lamond AI, Swamy M (2021). “Tissue environment, not ontogeny, defines intestinal intraepithelial T lymphocytes”. eLife, 10, e70055 DOI: 10.7554/eLife.70055 Vandereyken M, James OJ, Swamy M (2020). “Mechanisms of activation of intestinal intraepithelial lymphocytes.” Mucosal Immunology, 13:721–31. DOI: 10.1038/s41385-020-0294-6 He S, Kahles F, Rattik S, Nairz M, McAlpine C, et al. ‘Gut Intraepithelial T Cells Calibrate Metabolism and Accelerate Cardiovascular Disease’. Nature 566: 115–19. DOI: 10.1038/s41586-018-0849-9. 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 Mahima Swamy Senior Lecturer m.swamy@dundee.ac.uk +44 (0)1382 388615 Second supervisor Person Dr Alison McNeilly Principal Investigator A.D.McNeilly@dundee.ac.uk +44 (0)1382 388573

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. Colonization resistance refers to the ability of the microbiome in an organ to prevent colonization of that organ by pathogenic microorganisms [1]. For example, the gut microbiome of mice protect them from infection by the intestinal pathogen Salmonella typhimurium.  Loss of gut microbiota, by antibiotic treatment for example, can lead to susceptibility to infection. Despite some evidence for active antagonism against invading pathogens, mechanisms underlying colonization resistance are poorly understood. Understanding this phenomena could lead to ways to prevent and treat infection with microbes with anti microbial resistance (AMR). We propose to use Caenorhabditis elegans, a roundworm with a robust innate immune system, to identify microbiota species mediating colonization resistance to human microbial pathogens. The C. elegans gut, colonized first with individual or a consortia of gut microbiota derived (i) from C. elegans or (ii) from mice will be subsequently infected with pathogenic bacteria [2-4]. We will assess the contribution of the entire microbiota and individual species on colonization by flurescently labelled pathogens. Subsequently, we will use proteomics, liquid chromatography mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) approaches to identify soluble mediators of active antagonism and inhibitory metabolites. We will use worms lacking innate immune mechanisms to understand the effect of host genetics on colonization resistance offered by the gut microbiome [5].  C. elegans provides a genetically and optically tractable model to study colonization in a short amount of time. The PhD student will acquire training in C. elegans maintenance, microbiome colonization and infection. The student will also receive training in LC-MS and GC-MS analyses of individual bacterium and complex, multi-species samples.  The student will be provided additional training in scientific writing, statistical analyses and data management at University of Dundee in addition to mentoring support throughout and during career transition. REFERENCE: 1. Microbiota-mediated colonization resistance: mechanisms and regulation. Nat Rev Microbiol. 2023 Jun;21(6):347-360. doi: 10.1038/s41579-022-00833-7. PMID: 36539611. 2. CeMbio – The Caenorhabditis elegans Microbiome Resource. G3 (Bethesda). 2020 Sep 2;10(9):3025-3039. doi: 10.1534/g3.120.401309. PMID: 32669368. 3. Olfactory basis for essential amino acid perception during foraging in Caenorhabditis eleganseLife13:RP101936https://doi.org/10.7554/eLife.101936.1 4. Nutritional and host environments determine community ecology and keystone species in a synthetic gut bacterial community. Nat Commun. 2023 Aug 8;14(1):4780. doi: 10.1038/s41467-023-40372-0. PMID: 37553336. 5. Neuronal GPCR controls innate immunity by regulating noncanonical unfolded protein response genes. Science. 2011 May 6;332(6030):729-32. doi: 10.1126/science.1203411. Epub 2011 Apr 7. PMID: 21474712. 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 Varsha Singh Senior Lecturer and Royal Society Wolfson Fellow vsingh001@dundee.ac.uk +44 (0)1382 388898 Second supervisor Person Dr Daniel Neill Senior Lecturer dneill001@dundee.ac.uk +44 (0)1382 388899

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. Protein homeostasis and the regulation of protein degradation by the proteasome are fundamental cellular processes that maintain health by ensuring the proper synthesis, folding, and degradation of proteins. The failure of proteostasis is at the core of pathologies like neurodegeneration, a leading cause of disability, dependency, and death globally. Despite its critical importance, the molecular mechanisms that control protein homeostasis and proteasome function remain poorly understood. The Rousseau lab is interested in developing new technologies to explore the mechanistic control of proteasome variants in health and disease. The proteasome consists of a 20S core particle, which houses the proteolytic sites, and one or two regulatory particles (RPs) that recognise, unfold, and translocate substrates into the 20S for degradation. The primary RP, known as the 19S, mediates ubiquitin-dependent protein degradation and is commonly referred to as the conventional proteasome. Alternative RPs, such as PA28 and PA200, regulate ubiquitin-independent degradation and play key roles in immune response and nuclear integrity, respectively. Another layer of complexity is the existence of cell-type and context-dependent proteasome variants that diversify its functional repertoire, allowing adaptation to various cellular contexts. One of our main goals is to define the spatio-temporal regulation of proteasome assembly and activity in health, stress and diseases using both yeast and mammalian systems. This includes assembly and regulation of the poorly characterised alternative forms of the proteasome. The PhD project aims to (1) engineer the proteasome to develop innovative tools for monitoring the assembly of its alternative forms in living cells, (2) use these tools to uncover the mechanistic details of proteasome variant assembly, and (3) examine how stress and disease conditions impact proteasome variant assembly. The project offers training in cutting-edge technologies, including cell engineering (CRISPR-Cas9 editing of proteasome genes), molecular biology (proteasome and protein degradation assays), and high-resolution confocal microscopy (proteasome dynamics), applied to both yeast and mammalian systems. Recent lab contributions:    Williams, T. D., Winaya, A., Joshua, I., & Rousseau, A (2023) Proteasome assembly chaperone translation upon stress requires Ede1 phase separation at the plasma membrane iScience 27 doi:10.1016/j.isci.2023.108732 PMID: 38235332   Black, A., Williams, T. D., Soubigou, F., Joshua, I. M., Zhou, H., Lamoliatte, F., & Rousseau, A (2023) The ribosome-associated chaperone Zuo1 controls translation upon TORC1 inhibition EMBO Journal 42 e113240 doi:10.15252/embj.2022113240 PMID: 37984430   Agrotis A, Lamoliatte F, Williams TD, Black A, Horberry R, Rousseau A (2023) Multiple phosphorylation of the Cdc48/p97 cofactor protein Shp1/p47 occurs upon cell stress in budding yeast Life Sciences Alliance 6 doi:10.26508/lsa.202201642 PMID: 36693698   Williams, T., Cacioppo, R., Agrotis, A., Black, A., Zhou, H., & Rousseau, A (2022) Actin remodelling controls proteasome homeostasis upon stress Nature Cell Biology  doi:10.1038/s41556-022-00938-4 PMID: 35739319   Adrien Rousseau and Anne Bertolotti (2016) An evolutionarily conserved pathway controls proteasome homeostasis. Nature 536 184–189 PMID: 27462806   Ariane Hanssum, Zhen Zhong, Adrien Rousseau, Agnieszka Krzyzosiak, Anna Sigurdardottir and Anne Bertolotti (2014) An inducible chaperone adapts proteasome assembly to stress Mol. Cell  55 566–577 PMID: 25042801 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 Adrien Rousseau Principal Investigator/Senior Lecturer a.rousseau@dundee.ac.uk +44 (0)1382 384109

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 proteasome degrades most cellular proteins in a controlled and timely manner and thereby controls many key processes. Proteasomes are also essential for maintaining intracellular protein quality control by removing misfolded, damaged, or aggregation-prone proteins. Thus, the proteasome is vital in all eukaryotes, with its dysfunction associated with various human diseases, including cancer and neurodegeneration. However, the impact of disease-causing mutations in proteasome genes on proteasome integrity and cell survival remains poorly understood. The use of the budding yeast Saccharomyces cerevisiae as a model system has been instrumental to understanding the physiological functions and mechanistic attributes of the proteasome. Using budding yeast, this project will aim to discover new suppressor genes rescuing disease-causing mutations of the proteasome. This will involve (1) generating CRISPR-Cas9 mutations in proteasome genes and monitor their impact on proteasome assembly and activity, (2) performing a genome-wide suppressor screen in proteasome mutants to identify new genes rescuing proteasome mutations, and (3) unravelling the underlying mechanisms behind the phenotypic suppression of proteasome mutations. Finally, suppressor genes having the strongest phenotypic rescue of proteasome mutations in yeast will be investigated in human cells. This PhD project will employ genome editing, biochemistry, molecular and cell biology and proteasome engineering to discover new suppressor genes rescuing proteasome mutations observed in diseases. This will pave the way for defining new strategies to restore protein homeostasis in disease. 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 Adrien Rousseau Principal Investigator/Senior Lecturer a.rousseau@dundee.ac.uk +44 (0)1382 384109

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. Since the pioneering work of D’Arcy Thompson more than a century ago, it has become clear that shape and form play a major role in determining proper function of living organisms. Our understanding of molecular processes that underpin life has greatly improved since early 1900s. However, many questions remain open on how molecular-level regulation controls the development of functional tissue and organ scale structures. For example, for a healthy individual, it is not only necessary to have a liver, but it must be the right shape and size and positioned at the right place. Answering questions of how tissues and organs acquire and regulate their size and shape requires combining biochemical and mechanical processes and thus necessitates input from both physics and molecular biology. Physics of active matter, i.e. collections of agents such as cells that can convert chemical energy into directed motion, has emerged as a powerful tool for modelling collective behaviours of cells in various biological scenarios. The aim of this project will be to develop and study models of active matter of various levels of complexity to gain understanding how collectives of active agents respond to the presence of curvature and, ultimately, drive the shape formation. This will be done in close collaboration with the experimental lab of Prof Januschke who specialises in studying development in fruit fly embryos, a commonly used model system for exploring collective cell processes. The PhD student will gain training in cutting edge physics of active matter applied to biological systems and advance computational methods and techniques used to model cell and tissue scale biophysical processes. In addition, they will learn how to work in a cross-disciplinary environment and closely interact with researchers in different disciplines. Computational proficiency and ability to work in a diverse team are all highly transferable skills that would make the student competitive for positions both in academia and industry. We are, therefore, seeking a highly-motivated student with training in physics or applied mathematics who is willing to closely collaborate with experimental biology labs. 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 Rastko Sknepnek Professor r.sknepnek@dundee.ac.uk +44 (0)1382 385699 Second supervisor Person Professor Jens Januschke Professor j.januschke@dundee.ac.uk +44 (0)1382 386169