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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

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, 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. Am J Respir Cell Mol Biol, 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. Nat Cell Biol, 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. EMBO J, 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. J Gen Virol, 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. J Cell Sci, 110 ( Pt 22), 2819-2831.

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 Res, 22 (3), 270-278. http://doi.org/10.1093/nar/22.3.270

Conference papers

Hodgson, R., Allen, K.E., & Campbell, S. (2017). Characterisation of EIF2B bodies in vanishing white matter disease. JOURNAL OF NEUROCHEMISTRY, 142, 219-220.

Presentations

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., 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.

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