Our Cell Engineering research covers topics such as protein folding in the secretory pathway, regulation of membrane traffic, control of cell cycle, cytokinesis, compartmentalization of cellular signalling and cell engineering.
PhD Research Projects
Self funded opportunities
Defining the mechanism of abscission
Outline & aim
ESCRT proteins mediate membrane scission events involved in the down-regulation of ubiquitin-labelled receptors via the multivesicular body (MVB) pathway and in HIV budding from host cells. In addition, ESCRT proteins play a role in abscission, the final stage of cytokinesis. The ESCRT machinery is composed of four complexes: ESCRT-0, -I, -II and -III; and the modular composition of the ESCRT machinery is reflected in its various functions. At a precise time during cytokinesis, the ESCRT-I protein TSG101 and ESCRT-associated protein ALIX are recruited to the midbody through interactions with CEP55; TSG101 and ALIX in turn recruit ESCRT-III components. Thereafter, by a mechanism still not completely understood, ESCRT-III redistributes to the putative abscission sites, microtubules are severed and the daughter cells separate. However, the mechanisms by which this selective and specific redistribution of ESCRT proteins is regulated in space and time remain largely unsolved.
ESCRT components are phosphoproteins, so we reasoned that kinases and phosphatases are likely candidates for ESCRT regulation. We hypothesised that polo and aurora kinases and Cdc14 phosphatase may be potential regulators of ESCRT function due to their significant roles in controlling cytokinesis. This aspect of mitotic regulation of
ESCRT function will be investigated in this project, as we have shown that these kinases and phosphatases play a role; our challenge now is to define that role and to determine whether similar mechanisms operate in mammalian cells. This interface between signalling and trafficking is an important and active research theme worldwide, and you will join an active and collaborative group well versed in all the training aspects required for successful completion of a PhD.
The aim of the project is to define the role of aurora kinase, polo-like kinase and Cdc14 on ESCRT function in yeast and mammalian cells.
Yeast genetics; molecular biology; mammalian cell culture and cell biology; high resolution imaging/confocal microscopy
- M.S.Bhutta, B.Roy, G.W.Gould and C.J.McInerny Public Library of Science 1. (2014) In press. “Control of cytokinesis by polo and aurora kinases and Cdc14 phosphatase regulation of ESCRT proteins.”
- H.Neto, A.Kaupisch, L.L.Collins and G.W.Gould. Molecular Biology of the Cell (2013) 24, 3633-3674. “Syntaxin 16 is required for early stages in cytokinesis.”
Developing novel, combined strategies for peripheral nerve repair
Outline & aim
Peripheral nerve injuries are frequently seen following trauma or malignancy, with an incidence of 300000 cases in Europe following trauma alone. These injuries often result in functional deficits, and have a high impact on the patient’s quality of life, as well as placing a heavy financial burden on the state. Despite advances in surgical treatments, motor and sensory recovery following these injuries often remains incomplete. Here we help develop materials and apply a variety of biophysical techniques ranging from ultrasonic manipulation to 3D micro fabrication and microfluidics to create artificial guidance tubes, or tissues, that aid in nerve repair, with the aim of improving and assisting the outcome of surgical nerve repair.
The materials and devices are tested in vitro using a variety of models for peripheral and central nerve repair. The projects available range from basic materials science in collaboration with chemists (Prof G Cooke, Dr R Hartley, Prof M Salmeron-Sanchez), engineers for active nerve stimulation (Prof D Cumming) acoustic placement (Prof Cummings & Dr A Bernassau), microfluidics (Dr H Yin), to applied models (Prof A Hart). The implications of the different repair strategies on the cells genomic and proteomic response is being investigated in collaboration with the Glasgow Polyomics Facility (Dr R Burchmore, P Herzyk). This work is very much interdisciplinary, and adventurous, and requires not only a good foundation in basic molecular and cell biology, but also a willingness to learn the language and science of chemists, materials scientists, engineers and surgeons.
The project will vary depending on the applicants abilities and specific interests, the techniques and supervisors mentioned below are those with whom Dr Riehle collaborates.
Primary cell culture, molecular biology, imaging, image analysis, then depending on the specific project collaboration with engineers, chemists or physicists to make materials - synthetic organic chemistry - micro fabrication - electronic engineering - acoustic engineering.
- Cortese, B., Gigli, G., & Riehle, M. (2009). Mechanical Gradient Cues for Guided Cell Motility and Control of Cell Behavior on Uniform Substrates. Advanced Functional Materials, 19(18), 2961–2968
- Donoghue, P. S., Sun, T., Gadegaard, N., Riehle, M. O., & Barnett, S. C. (2013). Development of a Novel 3D Culture System for Screening Features of a Complex Implantable Device for CNS Repair. Molecular Pharmaceutics. doi:10.1021/mp400526n
- Caldwell, S. T., Maclean, C., Riehle, M., Cooper, A., Nutley, M., Rabani, G., … Cooke, G. (2014). Protein-mediated dethreading of a biotin-functionalised pseudorotaxane. Organic & Biomolecular Chemistry, 12(3), 511–6. doi:10.1039/c3ob41612g
- Gesellchen, F., Bernassau, a L., Déjardin, T., Cumming, D. R. S., & Riehle, M. O. (2014). Cell patterning with a heptagon acoustic tweezer - application in neurite guidance. Lab on a Chip, 19, 2266–2275. doi:10.1039/c4lc00436a
- Martin, C., Dejardin, T., Hart, A., Riehle, M. O., & Cumming, D. R. S. (2013). Directed Nerve Regeneration Enabled by Wirelessly Powered Electrodes Printed on a Biodegradable Polymer. Advanced Healthcare Materials, 1–6. doi:10.1002/adhm.201300481
- Nikukar, H., Reid, S., Tsimbouri, P. M., Riehle, M. O., Curtis, A. S. G., & Dalby, M. J. (2013). Osteogenesis of mesenchymal stem cells by nanoscale mechanotransduction. ACS Nano, 7(3), 2758–67. doi:10.1021/nn400202j
Molecular Control of Mesenchymal Stem Cell Differentiation to Fat and Bone by Anti-Diabetic Drugs
Outline & aims
Bone health is impaired in both type 1 and type 2 diabetes mellitus (T1DM and T2DM) and an improved understanding of impaired bone health is a major unmet need in the field of diabetes mellitus (DM). Bone health is compromised during DM due to a shift in the balance of differentiation of mesenchymal stem cells (MSCs) from bone formation towards fat. We therefore aim to determine the molecular and cellular control of MSC differentiation to either fat (adipogenesis) or bone (osteogenesis) in the context of anti-diabetic drug treatment. This is important because the widely-used drug, metformin, has been reported to have anabolic effects on bone whereas other insulin-sensitising drugs, such as the thiazolidinediones (TZDs), reduce bone mineral density with a corresponding increase in marrow fat and fracture incidence [1,2]. This differential effect of commonly encountered anti-diabetic drugs on osteogenesis and adipogenesis needs further study as it may lead to a more effective approach to the combined management of bone health and glucose homeostasis in people with DM.
As many anti-diabetic drugs have been reported to influence AMP-activated protein kinase (AMPK) activity, which has been reported to alter bone formation , our working hypothesis is that AMPK signalling pathway plays a cardinal role in regulating these processes through the regulation of expression of Runx2 and PPAR? transcription factors. We will therefore determine the role of AMPK in the control of murine (pluripotent CH310T1/2 cells ) and human models (human bone marrow-derived MSCs) of MSC differentiation in response to osteogenic (metformin) and adipogenic (TZD) anti-diabetic drug treatment.
Stem cell culture; light microscopy; confocal microscopy; immunofluorescence; reporter genes; western blotting
- Muruganandan, S., Roman, A.A. and Sinal, C.J. (2009). Adipocyte differentiation of bone marrow-derived mesenchymal stem cells: cross talk with the osteoblastogenic program. Cell Mol Life Sci 66, 236-53.
- Betteridge, D.J. (2011). Thiazolidinediones and fracture risk in patients with Type 2 diabetes. Diabet Med 28, 759-71.
- Shah, M., Kola, B., Bataveljic, A., Arnett, T.R., Viollet, B., Saxon, L., Korbonits, M. and Chenu, C. (2010). AMP-activated protein kinase (AMPK) activation regulates in vitro bone formation and bone mass. Bone 47, 309-19.
- Reznikoff, C.A., Brankow, D.W. and Heidelberger, C. (1973). Establishment and characterization of a cloned line of C3H mouse embryo cells sensitive to postconfluence inhibition of division. Cancer Res 33, 3231-8.
Molecular mechanics of clustering and gating in plant ion channels
Outline & aim
The organisation of ion channels in eukaryotic membranes is intimately connected with their activity, but the mechanics of the connections are, in general, poorly understood. Both in animals and plant, many ion channels assemble in discrete clusters that localise within the surface of the cell membrane. The clustering of the GORK channel — responsible for potassium efflux for stomatal regulation in the model plant Arabidopsis — is intimately connected with its gating by extracellular K+. Recent work from this laboratory yielded new insights into the processes linking K+ binding within the GORK channel pore to clustering of the channel proteins.
This project will explore the physical structure of GORK that determines its self-interaction as a function of the K+ concentration with the aim of understanding its integration with the well-known mechanics of channel gating.
The student will gain expertise in molecular biological methods, and a deep grounding in the concepts of membrane transport, cell biology and physiology. Skills training will include in-depth engagement in molecular biology, protein biochemistry and molecular genetic/protein design, single-cell imaging and fluorescence microscopy, and single-cell recording techniques of electrophysiology using heterologous expression in mammalian cell systems and in plants.
- Lefoulon, et al. (2014) Plant Physiol 166, 950-75
- Eisenach, et al. (2012) Plant J 69, 241-51
- Dreyer & Blatt (2009) Trends Plant Sci 14, 383-90
Photoregulation of plant hormone trafficking and signalling
Outline & aim
The phytohormone auxin (indole acetic acid) is instrumental for directing and shaping plant growth and form. Understanding how this chemical growth regulator controls plant development will have important implications for manipulating plant growth for agronomic gain. Auxin trafficking is profoundly influenced by many abiotic factors, including light. For instance, phototropin receptor kinases (phot1 and phot2) function to redirect auxin fluxes that are required to reorientate plant growth toward or away from light. The phot1-interacting protein Non-Phototropic Hypocotyl 3 (NPH3) is essential for establishing these light-driven auxin movements. However, the mode of action of NPH3 and how it functions to regulate transporter activity remains poorly understood.
This project aims to spatially dissect the site(s) of NPH3 action and how it impacts the subcellular trafficking and function of known auxin transporter proteins implicated in phototropism. Work is also focussed on characterising a newly identified NPH3 protein (NPH3-like, NPH3L) that interacts directly with phot1. Functional characterisation of NPH3, NPH3L and its homologues will provide new insights into the photoregulation of auxin trafficking and signalling associated with phototropism and other phototropin-mediated responses.
This proposal is focused on characterising the molecular processes that integrate light and phytohormone signalling, two important agronomic processes associated with manipulating plant growth and optimising photosynthetic efficiency. Both these research areas fall squarely within the strategic priorities of Food Security, Living with Environmental Change and Crop Science. The project will provide excellent training in a range of techniques associated with molecular biology, cell biology, genetics and biochemistry. Training will also be given in key skills including teaching, project-management and science communication. Additionally, the student will have the opportunity to attend and present their research at the international photobiology meetings e.g. Gordon Research Conference in Photosensory Receptors and Signal Transduction, Galveston, Texas in 2016 (which I will chair).
- CHRISTIE, J.M. (2007) Phototropin blue-light receptors. Annu. Rev. Plant Biol. 58, 21-45.
- Sullivan, S., Thomson, C.E., Kaiserli, E. and Christie J.M. (2009) Interaction specificity of Arabidopsis 14-3-3 proteins and phototropin receptor kinases. FEBS Lett. 583, 2187-2193.
- Christie, J.M., Richter, G., Yang, H., Sullivan, S., Thomson, C.E., Lin, J., Tiapiwatanakun, B., Ennis, M. Kaiserli, E., Lee, O.R., Adamec, J., Peer, W.A. and Murphy, A.S. (2011) Phot1 inhibition of ABCB19 primes lateral auxin fluxes in the shoot apex required for phototropism. PLoS Biol., 9(6): e1001076.
- CHRISTIE, J.M. and MURPHY, A.S. (2013) Shoot phototropism in higher plants: New light through old concepts. Am. J. Bot. 100, 35-46.
Regulation of plant nuclear architecture by light
Outline & aim
Light is essential for plant growth, development and photoprotection. One of the primary sites where light regulates major cellular processes is the nucleus. We are interested in elucidating how light stimulates the accumulation of photoreceptors and signalling components in nuclear micro-domains to regulate gene expression, chromatin remodelling and DNA damage repair. The student will investigate how nuclear compartmentalisation correlates with changes in the expression of growth promoting genes in response to light.
A series of approaches will be used depending on the interests and background of the applicant: Gene expression analysis (qRT-PCR, ChIP), molecular cloning, protein interactions studies (Y2H, co-immunoprecipitation), protein characterisation (heterologous expression and purification), cell biology (confocal microscopy), plant genetics and plant physiology.
The role of EPAC1 in the control of cytokine signalling in vascular endothelial cells
Outline & aims
We and others [1-3] have found that the cyclic AMP-activated signalling protein EPAC1 (exchange protein activated by cyclic AMP 1) promotes protective functions in vascular endothelial cells (VECs), including promotion of endothelial barrier function and induction of protein suppressors of cytokine signalling (eg SOCS3), and therefore plays a vital role in maintaining the health of the vasculature.
It is now clear that interactions with cellular binding proteins determine both the intracellular location and enzyme activity of EPAC1. For example, the cytoskeleton-associated, MAP1a-LC2 protein , recruits EPAC1 to microtubules and enhances its activity, whereas the nuclear-localised SUMO ligase, RanBP2 [5,6], suppresses EPAC1 activity at the nuclear pore complex.
Our aim now is to fully understand these control mechanisms with the long term goal of devising new therapies based on modulating protein interactions with EPAC1. Central to this goal is the new observation that EPAC1 becomes SUMOylated within the regulatory cyclic nucleotide binding domain (CNBD). Since the CNBD is responsible for direct activation by cyclic AMP and is also responsible for cytoskeletal recruitment through MAP1a-LC2, then SUMOylation represents a powerful new control mechanism for controlling EPAC1 localisation and activity.The student will therefore determine:
- The effects of SUMOylation on EPAC1 activity, subcellular localisation and interaction with regulatory proteins
- Determine the role of EPAC1 SUMOylation on the regulation of cytokine signalling in vascular endothelial cells
Cell culture; light microscopy; confocal microscopy; immunofluorescence; reporter genes; western blotting
- Sands, W.A., Woolson, H.D., Milne, G.R., Rutherford, C. and Palmer, T.M. (2006). Exchange protein activated by cyclic AMP (Epac)-mediated induction of suppressor of cytokine signaling 3 (SOCS-3) in vascular endothelial cells. Mol Cell Biol 26, 6333-46.
- Yarwood, S.J., Borland, G., Sands, W.A. and Palmer, T.M. (2008). Identification of CCAAT/enhancer-binding proteins as exchange protein activated by cAMP-activated transcription factors that mediate the induction of the SOCS-3 gene. J Biol Chem. 283, 6843-53.
- Borland, G., Smith, B.O. and Yarwood, S.J. (2009). EPAC proteins transduce diverse cellular actions of cAMP. Br J Pharmacol 6, 6.
- Gupta, M. and Yarwood, S.J. (2005). MAP1A light chain 2 interacts with exchange protein activated by cyclic AMP 1 (EPAC1) to enhance Rap1 GTPase activity and cell adhesion. J Biol Chem 280, 8109-16.
- Gloerich, M., Vliem, M.J., Prummel, E., Meijer, L.A., Rensen, M.G., Rehmann, H. and Bos, J.L. (2011). The nucleoporin RanBP2 tethers the cAMP effector Epac1 and inhibits its catalytic activity. J Cell Biol 193, 1009-20.
- Liu, C., Takahashi, M., Li, Y., Dillon, T.J., Kaech, S. and Stork, P.J. (2010). The interaction of Epac1 and Ran promotes Rap1 activation at the nuclear envelope. Mol 30, 3956-69.
Our Centre for the Cellular Microenvironment at Glasgow is a new entity (2018) arising from the merger of the Centre for Cell Engineering (CCE) and the Microenvironments for Medicine (MiMe). We are focused on fostering education and training in research to develop microenvironments to investigate and instruct cellular behaviour including, but not solely, stem cell differentiation.
Our research is centred on exploring how cells respond to their environment by changes in behaviour, differentiation, metabolism and various aspects of development. Our goal is to apply the knowledge gained from our research to address key issues affecting (stem) cell biology. The Centre for the Cellular Microenvironment at Glasgow adopts an inter-disciplinary approach across the Institute of Molecular, Cell and Systems Biology (MCSB) in the College of Medical, Veterinary and Biological Sciences and the Bioengineering Group in the School of Engineering, which is part of the College of Science and Engineering. Cell-environment interactions, cell signalling, stem cell biology, cell, and protein structure and function at interfaces, bioengineering of gene regulation by microenvironments, nanoparticle technologies, synthetic biology to guide cell adhesion, cell sorting and translational approaches to take finding to clinical application.
PhD programmes typically last 3-4 years with research topics being allied to ongoing research within the Centre for the Cellular Microenvironment. Some projects are related to basic science and other projects are more focused on translational aspects of our research; but all projects integrate with our existing research themes. A variety of multi-disciplinary research approaches are applied within these research programmes, including biomedical engineering, protein engineering, biochemistry, molecular biology, biophysics, polyomics (genomics, transcriptomics, proteomics, metabolomics), biomaterials, bioinformatics and synthetic biology, as well as cellular imaging of biological functions.
Specific areas of interest include:
- Bioengineering the microenvironment
- Engineering approaches to control gene expression
- Bio-engineered interfaces
- Biomaterials, scaffolds and 3D printing
- Protein structure and function
- Protein engineering and application
- Cell sorting and characterisation
- Stem cell maintenance and differentiation
- Nanoparticles for theranostics
Specific areas of application are:
- Bone repair
- Nerve repair
- Sourcing of rare cells
- Blood Brain Barrier
- Mesenchymal stem cell niche
- Haematopoietic stem cell niche
See Glasgow Biomaterials Seminar for an idea about recent and current projects.
Our PhD programme provides excellent training in cutting edge technologies that will be applicable to career prospects in both academia and industry. Many of our graduates become postdoctoral research associates (Canada, USA, Europe and UK) while others go on to take up positions within industry either locally (e.g. Collagen Solutions, BioGelX) or overseas (e.g. Medtronic). We have strong national and international connections with many academic and industrial collaborators. Funds are available through the College of Medical, Veterinary and Biological Sciences or the College of Science and Engineering (depending on primary alignment) to allow visits to international laboratories, or industry where part of your project can be carried out. This provides an excellent opportunity for networking and increasing your scientific knowledge and skill set
All our postgraduate research students are allocated a supervisor who acts as the main source of academic support and research mentoring.
You may want to identify a potential supervisor and contact them to discuss your research proposal before you apply.
Fees and funding
- £4,260 UK/EU
- £20,150 outside EU
Prices are based on the annual fee for full-time study. Fees for part-time study are half the full-time fee.
Additional fees for all students:
- Submission by a research student £480
- Submission for a higher degree by published work £1,200
- Submission of thesis after deadline lapsed £300
- Submission by staff in receipt of staff scholarship £680
- Research students registered as non-supervised Thesis Pending students (50% refund will be granted if the student completes thesis within the first six months of the period) £270
- General Council fee £50
Depending on the nature of the research project, some students will be expected to pay a bench fee to cover additional costs. The exact amount will be provided in the offer letter.
A 10% discount is available to University of Glasgow alumni. This includes graduates and those who have completed a Junior Year Abroad, Exchange programme or International Summer School at the University of Glasgow. The discount is applied at registration for students who are not in receipt of another discount or scholarship funded by the University. No additional application is required.
- £4,195 UK/EU
- £19,500 outside EU
Prices are based on the annual fee for full-time study. Fees for part-time study are half the full-time fee.
Additional fees for all students:
- Fee for re-submission by a research student: £460
- Submission for a higher degree by published work: £1,050
- Submission of thesis after deadline lapsed: £250
- Submission by staff in receipt of staff scholarship: £730
- Research students registered as non-supervised Thesis Pending students (50% refund will be granted if the student completes thesis within the first six months of the period): £300
- Registration/exam only fee: £150
- General Council fee: £50
We offer a wide range of cutting-edge research facilities, including core facilities in
- fluorescence activated cell sorting analysis
- cell imaging and biophysical techniques, including NMR.
- protein characterization that consists of state of the art machinery for analysing protein structure and interactions
- mass spectrometry
- next generation sequencing
Our research spaces are state-of-the-art and span three buildings. Notably, The Centre for Cell Engineering is a collaboration between biologists, physical scientists, engineers and clinicians aiming to understand the cell / material interface and the micro / nano scale. And then building improved and new medical devices. In addition to increasing understanding of fundamental cell biology to new nano and micro material, the Centre aims to translate cutting-edge science to clinic.
Through their research interests in drug development, biotechnology and clinical applications, many of our project supervisors have strong links with industry. We also have strong academic conections with many international collaborators in universities and research institutes. Funds are available through the collage of MVLS to allow visits to international laboratories where part of your project can be carried out. This provides an excellent opportunity for networking and increasing your scientific knowledge and skill set.
The College of Medical, Veterinary and Life Sciences Graduate School provides a vibrant, supportive and stimulating environment for all our postgraduate students. We aim to provide excellent support for our postgraduates through dedicated postgraduate convenors, highly trained supervisors and pastoral support for each student.
Our over-arching aim is to provide a research training environment that includes:
- provision of excellent facilities and cutting edge techniques
- training in essential research and generic skills
- excellence in supervision and mentoring
- interactive discussion groups and seminars
- an atmosphere that fosters critical cultural policy and research analysis
- synergy between research groups and areas
- extensive multidisciplinary and collaborative research
- extensive external collaborations both within and beyond the UK
- a robust generic skills programme including opportunities in social and commercial training