Research projects

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Developing novel, combined strategies for peripheral nerve repair

Supervisor: Mathis Riehle

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.

Techniques: 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.

References

1. 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
2. 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
3. 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
4. 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
5. 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
6. 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

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Molecular mechanics of clustering and gating in plant ion channels

Supervisor: Michael Blatt

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.

Techniques: 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.

References

1. Lefoulon, et al. (2014) Plant Physiol 166, 950-75
2. Eisenach, et al. (2012) Plant J 69, 241-51
3. Dreyer & Blatt (2009) Trends Plant Sci 14, 383-90

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Regulation of plant nuclear architecture by light

Supervisor: Eirini Kaiserli

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.

Techniques: 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.

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Understanding how phototropin blue light receptor kinase signal from the plant plasma membrane

Supervisor: John Christie

Project description: The ability to enhance photosynthetic capacity remains a recognised bottleneck to improving plant productivity. Phototropin receptor kinases (phot1 and phot2) play an important role in this regard by coordinating multiple light-capturing processes. These include phototropism, chloroplast accumulation movement, stomatal opening, leaf flattening and positioning all of which influence a plant's photosynthetic competence by improving the efficiency of light capture and regulating gas exchange between leaves and the atmosphere. Modulating these processes offers considerable potential to alter plant growth through changes in photosynthetic performance.

Yet, our understanding of how these autophosphorylating kinases initiate signalling from the plasma membrane (PM) is far from complete. Information on their substrates has been limited by the lack of a means to identify their phosphorylation targets in vitro. Gatekeeper engineering can overcome this limitation. The gatekeeper residue within the kinase domain of phots can be engineered to accommodate non-natural ATP analogues such as N6-benzyl-ATPγS6. This modification enables thiophosphorylation of substrate targets that can be detected using specific antibodies. Using this approach, we have now been able to identify new substrate targets. We are therefore able to offer several projects in this area aimed at further charactering the role of receptor autophosphorylation and kinase signalling in the plant model Arabidopsis.

Techniques: The project will provide excellent training in a range of techniques associated with molecular biology, confocal imaging, genetics, and biochemistry. Training will also be given in key skills including teaching, project-management, and science communication.

References:

1. Christie et al. (2018) Plant Physiol. 176, 1015
2. Hart et al. (2019) PNAS 116, 12550
3. Papanatsiou et al. (2019) Science 363, 1456
4. Schanbel et al. (2018) J Biol Cem 293, 5613
5. Sullivan et al. (2021) Nat Commun 12, 6129
6. Waksman et al. (2023) Plant J 114, 390

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Overview

The 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).

Our goal is to apply the knowledge gained from our research to address key issues affecting (stem) cell biology. Our research is centred on exploring how cells respond to their environment by changes in behaviour, differentiation, metabolism and various aspects of development. 

The Centre for the Cellular Microenvironment at Glasgow adopts an interdisciplinary approach across the School of Molecular Biosciences in the College of Medical, Veterinary & Life Sciences and the Bioengineering Group in the School of Engineering, which is part of the College of Science & 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.

Research topics are 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 multidisciplinary 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 & Life Sciences or the College of Science & 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.

Study options

PhD

• Duration: 3/4 years full-time; 5 years part-time

Individual research projects are tailored around the expertise of principal investigators.

Integrated PhD programmes (5 years)

Our Integrated PhD allows you to combine masters level teaching with your chosen research direction in a 1+3+1 format. 

International students with MSc and PhD scholarships/funding do not have to apply for 2 visas or exit and re-enter the country between programmes. International and UK/EU students may apply.

Year 1

Taught masters level modules are taken alongside students on our masters programmes. Our research-led teaching supports you to fine tune your research ideas and discuss these with potential PhD supervisors. You will gain a valuable introduction to academic topics, research methods, laboratory skills and the critical evaluation of research data. Your grades must meet our requirements in order to gain entry on to your pre-selected PhD research project. If not, you will have the options to pay outstanding MSc fees and complete with masters degree only.

Years 2, 3 and 4

PhD programme with research/lab work, completing an examinable piece of independent research in year 4.

Year 5

Thesis write up.

MSc (Research)

• Duration: 1 year full-time; 2 years part-time