Browsing by Author "Randles, Michael J."

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    Building a DMU e-Biology resource for health sciences’ students.
    (International Academy of Technology, Education and Development (IATED), 2017-11-18) Pena-Fernandez, A.; Sgamma, Tiziana; Young, Christopher N. J.; Randles, Michael J.; del Aguila, C.; Hurtado, C.; Evans, M. D.; Potiwat, N.; Izquierdo, F.; Pena, M. A.; Coope, J.; Armstrong, M.; Bhambra, Avninder S.
    The BSc Biomedical Science (BMS) programme at De Montfort University (DMU, Leicester, UK) is accredited by the Institute of Biomedical Science (IBMS). Students enrolled within this programme acquire highly sought after skills related with human health sciences to work in: pathology departments in hospitals; research institutions; biotechnology and pharmaceutical industries; and the education sector to name a few. The degree recruits a large number of students with currently around 600 students enrolled on this programme at DMU. Despite pre-entry requirements of knowledge of subjects related to human biology, biology or chemistry, we have noted that first year students require basic support in STEM subjects (biology, chemistry and mathematics) in modules such as “Basic Microbiology”, “Basic Anatomy and Physiology” and “Chemistry for the Biosciences”. This support is especially necessary for students that come from non-traditional routes such as Business and Technology Education Council (BTEC) routes. Moreover, usually topics related with microbiology and human diseases are challenging for students, often causing stress impacting their overall performance and experience. A group of BMS academics at DMU in conjunction with universities in the European Union (EU; e.g. University of San Pablo CEU, Spain) have started to design, create and develop a series of e-learning resources or units in human biology and BMS for undergraduate students that study health sciences degrees in the EU. These units are being uploaded onto the DMU web server (http://parasitology.dmu.ac.uk/) and will be only accessible for students from participating universities during the first phase of this project (2017/18 course) in which comprehensive feedback will be collected. This web server space has three sections or modules (theoretical section, virtual laboratory and microscope) in which the new e-learning resources will be preliminary accommodated. These units will be interactive and easy to follow, and will cover basic human biology (e.g. cells, cell structure), human anatomy and physiology, histology and basic microbiology, which will be embedded in a theoretical module named DMU e-Biology within the above URL link. They will include formative assessments and case studies throughout each unit. In addition, a series of practical units are being developed which describe routine practical elements in any biomedical laboratory such as laboratory materials, pipetting, molecular techniques (e.g. PCR), cell culture (e.g. use of biological safety cabinet) and histological techniques (e.g. use of microtome, staining techniques). The development of this teaching and learning resource will cover a gap in the traditional teaching and learning methods that are currently used and provided in the participating universities. The DMU e-Biology will aid to our undergraduate students to gain knowledge in human biology and microbiology by promoting self-learning. We consider that the DMU e-Biology will help overcome spatiotemporal, equipment and resource barriers. Additionally, it may help student retention as currently about a 10% of our first year students fail to continue BMS at DMU. Finally, the creation of the DMU e-Biology will also provide support to the DMU Student Retention and Attainment Strategy 2016-2020 through the DMU Student Learning Hub, which is currently under development.
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    Can new digital technologies support student retention and engagement?
    (Higher Education Academy (HEA), 2018-02-01) Pena-Fernandez, A.; Randles, Michael J.; Young, Christopher N. J.; Potiwat, N.; Bhambra, Avninder S.
    University students in their first year face a myriad of challenges such as information overload, poor individual attention and/or minimal interaction with their peers, which can impede their progress through higher education. These challenges, together with other factors, have an impact on student retention and progression that needs to be addressed. We have established a range of strategies to improve retention and progression of new Biomedical Science (BMS) students at De Montfort University (DMU, UK) in 2016/17, including an intensive induction week with social and networking events with academics to enhance the development of constructive relationships. We have also increased the number of lectures on foundation in biology, chemistry and maths, introduced more tutorials and created “surgery” hours or weekly drop-in sessions in each module. These strategies could have been translated into a reduction in the percentage of students that abandon their BMS studies after their first year from 10.3% (24 students) in 2015/16 to 6.5% (13 students) in 2016/17, according to DMU reporting software (Tableau). However, we have noted that some of our BMS students require more basic support in STEM subjects (biology and chemistry), particularly those students that enter from the Business and Technology Education Council (BTEC) pathway, despite having met university-set entry requirements and the modifications to the curriculum to cater for such students. To address these limitations, we have started to develop a complete e-learning package designed to enhance learning and underpin the fundamental concepts of biology and biochemistry. The development of the DMU e-Biology package started in 2017 and covers the specifications for AS and A level described by the Assessment and Qualifications Alliance (AQA, 2017) for human biology as well as the basic concepts delivered in our first year modules. The DMU e-Biology also has interactive case studies related to topics of interest for our students, such as alcohol abuse and biomarkers of disease in clinical samples, to encourage self-learning and autonomous work on the part of the user. The main aim of the virtual case studies is to facilitate the development of students’ abilities to critically evaluate and use evidence from the literature, skills that are invaluable to any scientist and indeed key for future generations of biomedical scientists. The final package will be publicly available on the DMU website (http://parasitology.dmu.ac.uk/ebiology/home.htm) in 2018, after reviewing student feedback. The availability of this resource prior to students starting their course may enable earlier engagement and improve student retention.
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    Genetic Background is a Key Determinant of Glomerular Extracellular Matrix Composition and Organization
    (Wolters Kluwer, 2015-04-20) Randles, Michael J.; Woolf, Adrian S.; Huang, Jennifer L.; Byron, Adam; Humphries, Jonathan D.; Price, Karen L.; Kolatsi-Joannou, Maria; Collinson, Sophie; Denny, Thomas; Knight, David; Mironov, Aleksandr; Starborg, Toby; Korstanje, Ron; Humphries, Martin J.; Long, David A.; Lennon, Rachel
    Glomerular disease often features altered histologic patterns of extracellular matrix (ECM). Despite this, the potential complexities of the glomerular ECM in both health and disease are poorly understood. To explore whether genetic background and sex determine glomerular ECM composition, we investigated two mouse strains, FVB and B6, using RNA microarrays of isolated glomeruli combined with proteomic glomerular ECM analyses. These studies, undertaken in healthy young adult animals, revealed unique strain- and sexdependent glomerular ECM signatures, which correlated with variations in levels of albuminuria and known predisposition to progressive nephropathy. Among the variation, we observed changes in netrin 4, fibroblast growth factor 2, tenascin C, collagen 1, meprin 1-a, and meprin 1-b. Differences in protein abundance were validated by quantitative immunohistochemistry and Western blot analysis, and the collective differences were not explained by mutations in known ECM or glomerular disease genes. Within the distinct signatures, we discovered a core set of structural ECM proteins that form multiple protein–protein interactions and are conserved from mouse to man. Furthermore, we found striking ultrastructural changes in glomerular basement membranes in FVB mice. Pathway analysis of merged transcriptomic and proteomic datasets identified potentialECMregulatory pathways involving inhibitionofmatrixmetalloproteases, liverXreceptor/retinoidX receptor, nuclear factor erythroid 2-related factor 2, notch, and cyclin-dependent kinase 5. These pathways may therefore alter ECM and confer susceptibility to disease.
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    Glomerular Cell Cross-Talk Influences Composition and Assembly of Extracellular Matrix
    (American Society of Nephrology, 2014-01-16) Randles, Michael J.; Byron, Adam; Humphries, Jonathan D.; Mironov, Aleksandr; Hamidi, Hellyeh; Harris, Shelley; Mathieson, Peter W.; Saleem, Moin A.; Satchell, Simon C.; Zent, Roy; Humphries, Martin J.; Lennon, Rachel
    The glomerular basement membrane (GBM) is a specialized extracellular matrix (ECM) compartment within the glomerulus that contains tissue-restricted isoforms of collagen IV and laminin. It is integral to the capillary wall and therefore, functionally linked to glomerular filtration. Although the composition of the GBM has been investigated with global and candidate-based approaches, the relative contributions of glomerular cell types to the production of ECM are not well understood. To characterize specific cellular contributions to the GBM, we used mass spectrometry–based proteomics to analyze ECM isolated from podocytes and glomerular endothelial cells in vitro. These analyses identified cell type–specificdifferences in ECM composition, indicating distinct contributions to glomerular ECM assembly. Coculture of podocytes and endothelial cells resulted in an altered composition and organization of ECM compared with monoculture ECMs, and electron microscopy revealed basement membrane–like ECM deposition between cocultured cells, suggesting the involvement of cell–cell cross-talk in the production of glomerular ECM. Notably, compared with monoculture ECM proteomes, the coculture ECM proteome better resembled a tissue-derived glomerular ECM dataset, indicating its relevance to GBM in vivo. Protein network analyses revealed a common core of 35 highly connected structural ECM proteins that may be important for glomerular ECM assembly. Overall, these findings show the complexity of the glomerular ECM and suggest that both ECM composition and organization are context-dependent.
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    Three-dimensional electron microscopy reveals the evolution of glomerular barrier injury
    (Nature, 2016-10-11) Randles, Michael J.; Collinson, S.; Mironov, Aleksandr; Koenigshausen, E.; Starborg, T.; Krendel, M.; Sellin, L.; Roberts, I.; Kadler, K.; Miner, J.; Lennon, Rachel
    Glomeruli are highly sophisticated filters and glomerular disease is the leading cause of kidney failure. Morphological change in glomerular podocytes and the underlying basement membrane are frequently observed in disease, irrespective of the underlying molecular etiology. Standard electron microscopy techniques have enabled the identification and classification of glomerular diseases based on two-dimensional information, however complex three-dimensional ultrastructural relationships between cells and their extracellular matrix cannot be easily resolved with this approach. We employed serial block face-scanning electron microscopy to investigate Alport syndrome, the commonest monogenic glomerular disease, and compared findings to other genetic mouse models of glomerular disease (Myo1e−/−, Ptpro−/−). These analyses revealed the evolution of basement membrane and cellular defects through the progression of glomerular injury. Specifically we identified sub-podocyte expansions of the basement membrane with both cellular and matrix gene defects and found a corresponding reduction in podocyte foot process number. Furthermore, we discovered novel podocyte protrusions invading into the glomerular basement membrane in disease and these occurred frequently in expanded regions of basement membrane. These findings provide new insights into mechanisms of glomerular barrier dysfunction and suggest that common cell-matrix-adhesion pathways are involved in the progression of disease regardless of the primary insult.