Dr Elizabeth Allen BSC, PhD, DipRCPath
Senior Lecturer in Biomedical Science
Summary
I studied for a BSc degree in Biochemistry at Bath University, followed by a PhD in Virology from Glasgow University and postdoctoral positions in research institutions in Glasgow and London. My research work was focused on transcription factor activation of gene expression in viral systems and cancer.
I then moved to the pharmaceutical industry, where I was involved in identifying genes from the human genome sequence which were suitable candidates for drug development. Since 2007 I have been working as a HCPC registered Clinical Scientist in diagnostic genetics in the NHS. I have worked in a number of clinical areas, ranging from haemostasis to metabolic disorders.
I was appointed as a lecturer at Sheffield Hallam University in May 2015.
About
I studied for a BSc degree in Biochemistry at Bath University, followed by a PhD in Virology from Glasgow University. My PhD project investigated how viral proteins activate gene transcription. I continued my research work investigating how transcription factors activate gene expression in cancer, working as a postdoctoral research associate at institutions in Glasgow and London.
I then moved to the pharmaceutical industry, working for three different pharmaceutical and biotech companies. The human genome sequencing project had just been completed. I was involved in several research projects trying to discover previously unidentified genes from the human genome sequence, which would be suitable targets for drug development.
Since 2007 I have been working as a HCPC registered Clinical Scientist in diagnostic genetics in the NHS, firstly in Manchester and more recently at Sheffield Children's Hospital. I have worked in a number of clinical areas, ranging from haemostasis to metabolic disorders. I was appointed as a lecturer at Sheffield Hallam University in May 2015, and I am teaching several subjects in biomedical sciences, including clinical chemistry, blood sciences, cancer and biology of disease.
Investigation of the molecular mechanisms of Vanishing White Matter Disease
Investigation of epigenetic mechanisms controlling gene transcription
Teaching
Research
Characterisation of the importance of eIF2B bodies in CACH/VWM disease
The initiation phase of protein synthesis is a key regulatory step in gene expression. One of the major control points in the translation initiation pathway is catalysed by the guanine nucleotide exchange factor eIF2B. In recent years a fatal human disease known as leukoencephalopathy with vanishing white matter (VWM) has been linked to mutations in all five subunits of eIF2B. The mechanism of pathogenesis of VWM is not clearly understood. The pathophysiology of VWM shows a central role for glial cells in the disease mechanism; however why oligodendrocytes and astrocytes are more affected than other cell types when eIF2B is required for all protein synthesis is unknown.
The key regulatory complex eIF2B and the G protein eIF2 co-localise to a specific cytoplasmic focus, termed eIF2B bodies. These bodies represent sites where the activity of eIF2B is controlled and regulated. This suggests that eIF2B bodies play an important role during active translation. We have recently identified a discrete localisation pattern for eIF2B subunits in glial cells. The effect of VWM mutations on the formation of these bodies in glial cells will be investigated to determine their functional impact.
We will use microscopy techniques such as FRET and FRAP to analyse eIF2B complexes.
Determination of the translational profile of VWM mutants in glial cells
Ribosome profiling is a method based on deep sequencing of ribosome-protected mRNA fragments. This allows the identification and quantification of the RNA molecules which are being actively translated within a cell. We aim to use CRISPR-cas9 technology to introduce mutant forms of the eIF2B subunits into glial cells. These cells will then be analysed using ribosome profiling, in order to determine the translational profile of glial cells in the presence and absence of common VWM mutations. This may highlight additional pathways underlying the mechanism of disease in these cells.
Dr L Crookes, Sheffield Diagnostic Genetics Service, Sheffield Children's NHS Foundation Trust
Publications
Journal articles
Hanson, F., Hodgson, R.E., Ribeiro de Oliveira, M.I., Allen, E., & Campbell, S. (2022). Regulation and function of elF2B in neurological and metabolic disorders. Bioscience Reports, 42 (6). http://doi.org/10.1042/BSR20211699
Duckett, C.J., Hargreaves, K.E., Rawson, K.M., Allen, K.E., Forbes, S., Rawlinson, K.E., ... Lacey, M. (2021). Nights at the museum: integrated arts and microbiology public engagement events enhance understanding of science whilst increasing community diversity and inclusion. Access Microbiology, 3 (5). http://doi.org/10.1099/acmi.0.000231
Norris, K., Hodgson, R., Dornelles, T., Allen, K.E., Abell, B., Ashe, M.P., & Campbell, S.G. (2020). Mutational analysis of the alpha subunit of eIF2B provides insights into the role of eIF2B bodies in translational control and VWM disease. Journal of Biological Chemistry. http://doi.org/10.1074/jbc.RA120.014956
Little, L.D., Carolan, V.A., Allen, K.E., Cole, L.M., & Haywood-Small, S.L. (2020). Headspace analysis of mesothelioma cell lines differentiates biphasic and epithelioid sub-types. Journal of Breath Research, 14 (4), 046011. http://doi.org/10.1088/1752-7163/abaaff
Hodgson, R.E., Varanda, B.A., Ashe, M.P., Allen, K.E., & Campbell, S. (2019). Cellular eIF2B subunit localisation: implications for the integrated stress response and its control by small molecule drugs. Molecular biology of the cell, 30 (8), 933-1049. http://doi.org/10.1091/mbc.E18-08-0538
Coffey, A.J., Durkie, M., Hague, S., McLay, K., Emmerson, J., Lo, C., ... Bandmann, O. (2013). A genetic study of Wilson's disease in the United Kingdom. Brain : a journal of neurology, 136 (Pt 5), 1476-1487. http://doi.org/10.1093/brain/awt035
Temple, R., Allen, E., Fordham, J., Phipps, S., Schneider, H.C., Lindauer, K., ... Jupp, R. (2001). Microarray analysis of eosinophils reveals a number of candidate survival and apoptosis genes. American journal of respiratory cell and molecular biology, 25 (4), 425-433. http://doi.org/10.1165/ajrcmb.25.4.4456
Morris, L., Allen, K.E., & La Thangue, N.B. (2000). Regulation of E2F transcription by cyclin E-Cdk2 kinase mediated through p300/CBP co-activators. Nature cell biology, 2 (4), 232-239. http://doi.org/10.1038/35008660
de la Luna, S., Allen, K.E., Mason, S.L., & La Thangue, N.B. (1999). Integration of a growth-suppressing BTB/POZ domain protein with the DP component of the E2F transcription factor. The EMBO journal, 18 (1), 212-228. http://doi.org/10.1093/emboj/18.1.212
Allen, K.E., & Everett, R.D. (1997). Mutations which alter the DNA binding properties of the herpes simplex virus type 1 transactivating protein Vmw175 also affect its ability to support virus replication. The Journal of general virology, 78 ( Pt 11), 2913-2922. http://doi.org/10.1099/0022-1317-78-11-2913
Allen, K.E., de la Luna, S., Kerkhoven, R.M., Bernards, R., & La Thangue, N.B. (1997). Distinct mechanisms of nuclear accumulation regulate the functional consequence of E2F transcription factors. Journal of cell science, 110 ( Pt 22), 2819-2831. http://doi.org/10.1242/jcs.110.22.2819
Buck, V., Allen, K.E., Sørensen, T., Bybee, A., Hijmans, E.M., Voorhoeve, P.M., ... La Thangue, N.B. (1995). Molecular and functional characterisation of E2F-5, a new member of the E2F family. Oncogene, 11 (1), 31-38.
Tyler, J.K., Allen, K.E., & Everett, R.D. (1994). Mutation of a single lysine residue severely impairs the DNA recognition and regulatory functions of the VZV gene 62 transactivator protein. Nucleic acids research, 22 (3), 270-278. http://doi.org/10.1093/nar/22.3.270
Conference papers
Hanson, F., Hodgson, R., De Oliveira, M., Cross, A., Allen, K.E., & Campbell, S. (2021). Differential eIF2B-mediated translational control between neuronal and glial cells during stress and disease. GLIA, 69, E220.
Hodgson, R., Allen, K.E., & Campbell, S. (2017). Characterisation of EIF2B bodies in vanishing white matter disease. JOURNAL OF NEUROCHEMISTRY, 142, 219-220.
Book chapters
Searle, C., Andresen, B.S., Wraith, E., Higgs, J., Gray, D., Mills, A., ... Hobson, E. (2013). A Large Intragenic Deletion in the ACADM Gene Can Cause MCAD Deficiency but is not Detected on Routine Sequencing. In JIMD Reports. (pp. 13-16). Springer Berlin Heidelberg: http://doi.org/10.1007/8904_2013_216
Presentations
Oliveira, M., Cross, A., Campbell, S., & Allen, K.E. (2022). The role of eIF2Bɑ in the integrity of eIF2B bodies in glial and neuronal cells. Presented at: Translation IK, Sheffeld Hallam University
Hodgson, R., Campbell, S., & Allen, K. (2018). eIF2B subunits localise to distinct populations of eIF2B bodies that allow for differential regulation by the ISR. Presented at: Translation UK, The University of Manchester
Hodgson, R., Allen, K., & Campbell, S. (2016). eIF2B subcomplexes in cells linked to Vanishing White Matter Disease pathology. Presented at: Sheffield Glial Symposium, Sheffield Hallam University
Posters
Garrard, K., Campbell, S., & Allen, K.E. (2023). Paediatric ataxia and cell stress:The role of the unfolded protein response in paediatric ataxia. Presented at: Annual meeting of the British Paediatric Neurology Association, Edinburgh
Campbell, S., Oliveira, M., Cross, A., & Allen, K.E. (2022). The role of eIF2Bɑ in the integrity of eIF2B bodies in glial and neuronal cells. Presented at: Translational Control, Cold Spring Harbor Laboratories
Hanson, F., Allen, K.E., Cross, A., & Campbell, S. (2022). eIF2B localisation is regulated in a cell type specific manner during acute and chronic activity of the integrated stress response. Presented at: Translational Control, Cold Spring Harbor Laboratories
Oliveira, M., Campbell, S., Cross, A., & Allen, K.E. (2022). The role of eIF2Bɑ in the integrity of eIF2B bodies in glial and neuronal cells. Presented at: Translation UK, Sheffield Hallam University
Hodgson, R., Allen, K.E., & Campbell, S. (2022). The functional localisation of eIF2B: insight into pathophysiology of VWM disease. Presented at: Translation UK, Sheffield Hallam University
Campbell, S., Oliveira, M., & Allen, K.E. (2021). B-cell epitope prediction and Immunocytochemistry methodology for eIF2B detection in neuronal and glial cells. Presented at: Protein Synthesis and Translational Control, Virtual EMBL conference
Hodgson, R., Allen, K.E., & Campbell, S. (2021). VWM mutations can disrupt the localisation of eIF2B: A diagnostic tool for VWM? Presented at: Protein Synthesis and Translational Control, Virtual EMBL conference
Hodgson, R., Allen, K.E., & Campbell, S. (2021). VWM mutations can disrupt the localisation of eIF2B: A diagnostic tool for VWM? Presented at: Translation UK, Virtual conference
Hanson, F., Cross, A., Allen, K.E., & Campbell, S. (2021). Differential eIF2B-mediated translation control in neuronal and glial cells. Presented at: Translation UK, Virtual conference
Oliveira, M., Cross, A., Campbell, S., & Allen, K.E. (2021). B-cell epitope prediction and Immunocytochemistry methodology for eIF2B detection in astrocytes. Presented at: Translation UK, Virtual conference
Garrard, K., Allen, K., Campbell, S., Beauchamp, N., Panayi, M., & Mordekar, S. (2021). Genetic Diagnostic Rates in Paediatric Ataxia. Presented at: 47th Annual meeting of the British Paediatric Neurology Association, virtual
Campbell, S., Allen, K., & Hodgson, R. (2020). eIF2B bodies―Implications for the ISR and disease phenotypes. Presented at: Translational Control (Virtual), Cold Spring Harbor Laboratories
Hanson, F., Cross, A., Allen, K., & Campbell, S. (2020). Investigating the role of the delta (δ) subunit of eIF2B during stress and disease. Presented at: Cold Spring Harbor meeting: Translational Control (Virtual), Cold Spring Harbor Laboratories
Hanson, F., Allen, K., Cross, A., & Campbell, S. (2019). Investigating the role of the delta (δ) subunit of eIF2B during stress and disease. Presented at: XIV European Meeting on Glial Cells in Health and Disease, Porto, Portugal
Hanson, F., Cross, A., Allen, K., & Campbell, S. (2019). Investigating the role of the delta (δ) subunit of eIF2B during stress and disease. Presented at: Translation UK, University of Glasgow
Hodgson, R., Allen, K., Cross, A., & Campbell, S. (2019). The impact of eIF2B mutations and ISR-modifying drugs on eIF2B localisation. Presented at: Translation UK, University of Glasgow
Hodgson, R., Allen, K., & Campbell, S. (2018). eIF2B subunits localise to distinct populations of eIF2B bodies that allow for differential regulation by the ISR in cells linked to VWM. Presented at: Translational Control, Cold Spring Harbor Laboratories
Hodgson, R., Allen, K., & Campbell, S. (2017). eIF2B subcomplexes display differential control of translation initiation in cells directly affected by VWM. Presented at: Translation UK, University of Nottingham
Campbell, S., Hodgson, R., Allen, K., & Abreu Varanda, B. (2016). eIF2B SUB COMPLEXES EXIST IN CELLS LINKED TO VWM. Presented at: Translational Control, Cold Spring Harbor Laboratories, Long Island, USA
Hodgson, R., Allen, K., & Campbell, S. (2016). Characterisation of the Functional Significance of eIF2B Bodies in Leukoencephalopathy with Vanishing White Matter. Presented at: Translation UK, University of Surrey
Postgraduate supervision
Co-supervisor - Characterisation of the importance of eIF2B bodies in CACH/VWM disease and determination of the translational profile of VWM mutants in glial cells.