Our Research Impact and Innovation
The School of Molecular Biosciences has a strong track record of translating our research from bench to spin out. With the success of companies such as Keltic Pharma and Solasta Bio, and plans for a clinical trial in 2023, we are focusing on the translational areas of:
- Specialist green insecticides
- Pharmacology
- Bone regeneration
- Mitochondrial targeting
Research in these areas involves collaborations with stakeholders (NHS Greater Glasgow & Clyde, Scottish Enterprise), charities (Sir Bobby Charlton Foundation) and industrial partners (Bayer, BASF).
Professor Matt Dalby is the School Director of Innovation, Engagement and Enterprise, working with Claire Carberry to support innovative ideas by linking with useful contacts across the University and potential funding. Prof Dalby will strive to identify new REF cases and plans to initiate IEE training and activities over the new few months. If you would like to discuss IEE further, please contact Matthew.Dalby@glasgow.ac.uk
A number of impact cases are presented below.
Orthobioactive coatings (HealiOst)
Professors Manuel Salmerón-Sánchez and Matt Dalby have developed a novel bioactive polymer coating that can be applied to complex orthopaedic implant geometries using plasma polymerisation. The coating causes biologically correct organisation of the cell adherence protein fibronectin. As fibronectin is adsorbed it unfolds into a fibrillar confirmation forming biological networks and exposes the RGD cell adhesion domain and also the growth factor binding site in close proximity. This allows growth factors such as BMP2 to be bound to the growth factor site at very low yet highly efficient doses for stimulation of cells in the environment. BMP2 is currently widely used clinically but of great concern as it is administered at supraphysiological doses to achieve effect. Our technology allows for biologically safe doses to provide a greater and more targeted effect.
The full coating system was used clinically for the first time in 2017 with the successful treatment of Eva the dog, a veterinary patient from the Glasgow Small Animal Hospital. Being subject to a severe fracture following a car accident, Eva was at the stage of having her leg amputated when HealiOst was deployed in a last effort to repair the bone and save her leg. Eva’s veterinary surgeon, Mr William Marshall, used bone graft coated with HealiOst and BMP-2 to fill the 2cm bone gap with the result being full repair of the bone within 6 weeks of implantation. The team have secured ERC funding to treat further veterinary cases and are pursuing human use of this technology through funding provided by Find a Better Way – a landmine charity focussed on helping the survivors of landmine blast injuries. A patent has been filed for HealiOst and collaborations with partner organisations are focussed on clinical translation for human orthopaedic indications.
NanoKick bioreactor
Professors Matt Dalby and Stuart Reid (University of Strathclyde) have developed the Nanokick bioreactor, currently subject to patent application. It uses tiny vibrational movements to mechanically stimulate mesenchymal stem cells to form bone in vitro. Unlike other bioreactors it uses standard cell culture consumables (e.g. 6 well plates and flasks) making it easy to integrate into standard cell culture protocols. Further, it requires no complex media formulations / supplements to achieve osteogenesis – Nanokicking alone is enough to consistently stimulate osteogenesis in 2D or 3D culture. The team are currently working with partners including the Scottish Blood Transfusion Service to use Nanokicking to manufacture an off the shelf injectable cell therapy for bone repair as part of their Find a Better Way funded project aiming to help landmine survivors. The need for clinically implantable bone cells arises from bone being the second most grafted tissue behind blood and existing products / techniques having limitations in supply or regenerative potential. Data from in vivo studies suggests that Nanokicked cells are more effective at bone repair than standard mesenchymal stem cells due to their phenotypic priming to form osteoblasts. As part of the project the team are progressing towards first-in-human trial of the cell therapy with funding already secured from Find a Better Way.
Using Drosophila for kidney disease therapeutics
Professor Julian Dow is at the forefront of research in ‘omics, ion transport and kidney function in the genetic model Drosophila melanogaster (1,2). This has shown commonality of kidney function between humans and Drosophila, allowing the modelling of kidney disease using Drosophila, with the aim of therapeutics development. The group has now developed a successful model for kidney stones in the fly ‘kidney’ (3, 4) with funding from National Institutes of Health, USA as well as BBSRC Sparking Impact funds that enabled development of in vivo screening of kidney stone formation using the fly kidney.
The key advantage of the Drosophila system is that it permits rapid, reproducible formation of stones in an intact, transparent tissue,so allowing informative analysis and compound screens to be performed for the first time. He and Professor Shireen Davies are also partners in an EU-funded H2020 Marie Curie Innovative Training Network on renal development and disease, using Drosophila to model other kidney diseases including Inborn Errors of Metabolism.
References
1 Proc. Natl Acad.Sci. USA 111, 14301-14306 (2014).
2 Nat Commun 6, 6800, doi:10.1038 ncomms7800 ncomms7800 .(2015).
3 Am. J. Physiol.-Renal Physiology 303, F1555-F1562 (2012).
4 J. Urol., doi:S0022-5347(13)03645-8 (2013).
Stress tolerance in crops
Researchers in the group of Professor Anna Amtmann have discovered a protein in the chromatin of plants that attenuates gene induction under salt or water stress, and enhances biomass. Before publishing their results in The Plant Cell [1] they discussed their discovery with Matthew Hannah, project leader at Bayer CropScience, Gent, Belgium.
Following independent testing of the transgenic lines in the Bayer laboratories, a licence agreement was achieved between Bayer and UoG, and a common patent application was filed. Bayer provided bridging funds for the post-doctoral researcher at Glasgow during the negotiations, and they committed to a £0.5 M Industrial Partnership Award from the BBSRC. The 3-year project on the molecular and physiological functions of the gene is now well underway.
Professor Amtmann describes the experience as very positive. “The scientific feedback we are getting from Dr Hannah is well-informed and constructive, and it is exciting for us to follow the progress of our gene in the crop improvement programs at Bayer. It was hard work and sometimes nerve-wrecking to get to this stage but it in the end it is a net gain for all partners involved. Clearly, fundamental science and commercialisation can go hand-in-hand.”
[1] Perrella et al. (2013) Plant Cell 25: 3491-3505. doi:10.1105/tpc.113.114835
Developing greener ways of controlling pest insects
Professor Shireen Davies is currently leading the 14 -partner EU-funded nEUROSTRESSPEP consortium to develop novel and greener insecticidal agents based on insect neuropeptide mimetics. Neuropeptides are regulators of critical life processes in insects and comprise new insecticidal agents to selectively reduce the fitness of pest insects, whilst minimising detrimental environmental impacts. The project nEUROSTRESSPEP has developed insecticidal prototypes based on ‘omics, physiology and chemistry, as well as genetic pest management strategies.
Targetting receptors for short chain fatty acids to treat and metabolic and inflammatory diseases
In recent years Professor Graeme Milligan has been exploring ways in which mimicking the health beneficial effects of short chain fatty acids that are produced in high levels by the microflora could be applied to the production of ‘functional foods’, via either pre-biotic or pro-biotic strategies. In parallel with this effort Professor Milligan has been studying the underlying biology of the receptors that are activated by these receptors and whether they might be novel and tractable targets for the treatment of metabolic dysfunctions such as type II diabetes.
Publications stemming from this research have attracted great interest from both large and medium sized pharmaceutical companies. Professor Milligan was invited to travel to a number of companies to give presentations and discuss potential collaborations.
The most satisfactory potential partner in terms of providing each of potential funding, beneficial non-overlapping expertise and a history of previous links between Professor Milligan’s group and scientists employed by the company, was Astra-Zeneca.
Following discussions, Astra-Zeneca supported an Industrial Partnership Award (IPA) application led by Professor Milligan to BBSRC. This provides a total of £1.5 Million in funding over a 4 year period and Astra-Zeneca provides £150K in cash. The company has also provided a range of non-commercially available ligands and in return will gain pre-publication insights into which of the receptors for short chain fatty acids is most suitable to target as well as a number of animal models that will be generated within the project.
Provision of sensory neuronal cells to the pharma industry
The Centre for the Cellular Microenvironment was funded by the NC3Rs to address the DRGNet challenge as part of their CRACK IT open innovation programme. The aim of the DRGNet challenge was to identify sustainable sources of sensory neurons isolated from human dorsal root ganglia (hDRG). Pharma raised the challenge as recently several drugs for pain, that had been successful in animal testing, subsequently failed phase 1 human trials. Access to a local, affordable and reliable source of hDRG sensory neurons may enable the pharmaceutical industry to identify and discard early in development compounds destined to fail.
We formed a very capable team with expertise in cell isolation, maintenance and characterisation that was led by, from Glasgow, Prof Andrew Hart, Dr Mathis Riehle, David I Hughes and Mair Crouch, and Gareth Miles from St Andrews, alongside collaboration with the industrial partners Grünenthal GmbH (Aachen, D) and Metrion (Cambridge, UK). After ethics application, the ability to isolate the hDRG cells was established. The hDRG neurons were shown by several partners, including industry, to respond as expected to capsaicin, pH and ATP. The hDRG neurons show a similar distribution of immunological subtype markers as other mammals. Several different action potential response types, typical I/V curves and TTX insensitive sodium currents were regularly recorded allowing to fully characterise the usefulness of these cells for in vitro testing. We are currently in an early phase of our exit strategy for DRGNet Scotland.
Empowering Plant Science Education in Classrooms
Sci-Seedlets is an educational engagement with impact project for classrooms delivering fundamentals of plant physiology and plant science research to inspire the next generation of Plant Scientists.
Led by Dr Rucha Karnik, the multidisciplinary team of scientists in the University of Glasgow and Lancaster University works with school partners and artists to develop and evaluate a repertoire of resources aimed at transforming the traditional plant science curriculum into an engaging and interactive subject.
Sci-Seedlets encompass a repertoire of STEM-led educational resources conveying complex biological concepts using traditional paper-based and electronic interactive practical kits and cutting-edge virtual game formats. Embedded in ongoing research, Sci-Seedlets promote the importance of molecular plant science for addressing climate challenges and achieving food security by reducing water-use and improving plant health and lay the foundations for a more sustainable future.
The project is supported by the University of Glasgow Medical, Veterinary & Life Sciences (MVLS) College Innovation team through TRI-managed BBSRC funding, and the Public Engagement offices for a self-sustaining social enterprise. The project has received support from the Small Business Grants (SMB) fund, the University of Lancaster SCC, and grants from The Royal Society, BBSRC IAA (2021) and GKEF (2023).
In collaboration with the College of Arts, and the School of Education Sci-Seedlets resource development integrates sustainability and the concepts of equality, diversity and inclusion.
Publications
1) Baena, G. , Xia, L. , Waghmare, S. and Karnik, R. (2022) SNARE SYP132 mediates divergent trafficking of H+-ATPase AHA1 and antimicrobial PR1 during bacterial pathogenesis. Plant Physiology, 189(3), pp. 1639-1661.
2) Xia, L., Marques-Bueno, M. M., Bruce, C. G. and Karnik, R. (2019) Unusual roles of secretory SNARE SYP132 in plasma membrane H+-ATPase traffic and vegetative plant growth. Plant Physiology, 180(2), pp. 837-858.
3) Horaruang, W., Klejchová, M., Carroll, W., Blatt, M.R et al. (2022) Engineering a K+ channel ‘sensory antenna’ enhances stomatal kinetics, water use efficiency and photosynthesis. Nature Plants https://doi.org/10.1038/s41477-022-01255-23.
4) Papanatsiou, M., Petersen, J., Henderson, L., Wang, Y., Christie, J.M., And Blatt, M.R. (2019). Optogenetic Manipulation Of Stomatal Kinetics Improves Carbon Assimilation, Water Use, And Growth. Science 363, 1456-1459.
Mitotargin
Professor Kostas Tokatlidis and his research group from the School of Molecular Biosciences at the University of Glasgow, are developing Mitotargin, an innovative therapeutic or diagnostic agent targeting the mitochondria. This work has been supported by the TRI through Wellcome Trust, MRC and BBSRC funding.
The team behind Mitotargin have shown that targeting the mitochondria in a way that can modulate function and cell metabolism offers a promising therapeutic approach with potential to address unmet clinical needs including the treatment of therapy-resistant cancer, neurodegenerative and mitochondrial diseases.
Work to date has demonstrated that a variety of therapeutic and diagnostic agents including small molecules can be precisely delivered to intracellular mitochondria via Mitotargin. Furthermore, this approach has been shown to work even in compromised, membrane-damaged mitochondria (a hallmark of several human diseases). This is a significant improvement compared to existing mitochondria delivery strategies that are dependent on the intact nature of the inner mitochondrial membrane, and have so far been largely limited to small molecule delivery.
Finally, the team have shown that this unique dual property of cell penetration across the plasma membrane and specific targeting to the mitochondria can operate in multiple cell types to deliver agents that target the mitochondria and modulate function and cell metabolism.
As a platform technology, Mitotargin offers a promising therapeutic approach with potential to address unmet clinical needs including the treatment of therapy-resistant cancer, mitochondrial dysfunction in diseases such as neurodegeneration and genetic mitochondrial diseases.
Integrated Protein Analysis Facility
The Integrated Protein Analysis Facilty (formerly the Structural Biology and Biophysical Characterisation Facility), led by Dr Mads Gabrielsen, offers a wide range of biophysical techniques, such as structural analysis using x-ray crystallography or NMR, determination of binding affinities using isothermal calorimetry (ITC), surface plasmon resonance (SPR), or microscale thermophoresis (MST), and quality control of samples using circular dichroism (CD), multi-angle light scattering (MALS) and thermofluorescence. The facility also offers access to small-angle x-ray scattering (SAXS), and analytical ultracentrifugation (AUC). The IAP provides access to the equipment, as well as the expertise to process and analyse the data. We can also offer training in the use of the equipment and the underlying theory.
We provide the full range of techniques to external customers and are working closely with commercial companies and CROs as well as other academic institutions. The CD is particularly attractive to companies working with small compounds and peptide-mimetics, as the technique is non-invasive, and the samples recoverable. We deliver full reports and will have pre- and post-experiment meetings to ensure we provide a bespoke service.
Innovation, Engagement and Enterprise Toolkit for Researchers
How our research meets the world and impacts industry, stakeholders, clinicians, policy makers and so on is extremely important to us. Which is why we've pulled together an Innovation, Engagement and Enterprise Toolkit and key contacts to support our researchers.