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 Glasgow and London.
I then worked in the pharmaceutical industry, identifying genes from the human genome sequence which were suitable candidates for drug development. In 2003 I registered as a Clinical Scientist with the HCPC, working in diagnostic genetics until joining Sheffield Hallam University in 2015.
I teach on the BSc(Hons) Biomedical Science course, and a range of Masters’ courses. My research interest is in rare genetic disease; functional interpretation of genetic variants; and dysregulation of the unfolded protein response.
About
I studied for a BSc degree in Biochemistry at Bath University, followed by a PhD in Virology from Glasgow University. I studied how transcription factors activate gene expression in viruses and cancer, working as a postdoctoral research associate in Glasgow and London.
I then worked for three different pharmaceutical and biotech companies. The human genome sequencing project had just been completed. I was involved in research projects trying to discover previously unidentified genes from the human genome sequence, which would be suitable targets for drug development.
Since 2003 I have been working as a HCPC registered Clinical Scientist in diagnostic genetics in the NHS. I was appointed as a lecturer at Sheffield Hallam University in May 2015.
Senior Lecturer
Investigation of the molecular mechanisms of Vanishing White Matter Disease
Investigation of epigenetic mechanisms controlling gene transcription
Teaching
School of Biosciences and Chemistry
College of Health, Wellbeing and Life Sciences
I supervise a range of laboratory and bioinformatic projects, from undergraduate to postgraduate levels.
Biosciences
I use my industry and clinical experience in my teaching. I use problem-based and case-based scenarios to enhance students’ understanding of how theoretical concepts help scientists to diagnose, monitor and treat disease.
BSc (Honours)/MSci Biomedical Science
BSc (Honours)/MSci Biomedicine and Health Science
BSc (Honours)/MSci Biochemistry
BSc (Honours)/MSci Biology
MSc Pharmaceutical Analysis
MSc Pharmacology and Biotechnology
- Genes to Proteins Biochemistry in Action (module leader)
- Advanced Genetics (module leader)
- Biopharmaceuticals and Drug Discovery (module leader)
- Fundamentals of Biomedical Science
- Biomedical Science in Practice
- Disease, Diagnostics and Therapeutics
- Blood Sciences
- Professional and Scientific Practice
Research
The unfolded protein response (UPR) is a cellular signalling pathway which responds to stress caused by misfolded proteins, triggering three pathways which pause protein synthesis and increase expression of stress-responsive genes. This allows cells to either restore protein synthesis, or in the presence of chronic stress, induce cellular apoptosis.
The UPR is activated in a wide range of neurological diseases and it has been proposed that the ISR branch of the UPR is an ideal biomarker to monitor disease progression. My research involves studying skin cells which carry rare neurogenetic mutations and differentiating these cells into different cell types such as neurones or glial cells to investigate whether the mutations activate the UPR. We could then use these cell models to look at the effect of mutations in patient cells, to help in genetic diagnosis of rare disease.
The ISR also has a significant role in cancer, as it controls cellular responses to tumour stresses. Enhancement or inhibition of ISR signalling is a promising strategy for cancer therapy. Activation of the ISR also induces the formation of stress granules (SG), aggregates of protein and RNA within the cell cytoplasm. Inhibition of SG formation enhances cancer cell death and is therefore a potential therapeutic strategy.
eIF2B is a large protein complex made up of 5 subunits which is a master regulator of the ISR pathway. One of the eIF2B subunits, eIF2Bα,reacts to stress and regulates the activity of eIF2B.
We have shown that the eIF2Bα subunit binds to proteins which are needed to form SG and therefore may be a potential link between the ISR and SG formation. eIF2Bα expression is also linked to poor prognosis in some cancers such as lung cancer. We are collaborating with researchers at the Institute of Cancer Research to investigate ways in which cancer cells change the activity of eIF2Bα and therefore alter the cell’s sensitivity to anti-proliferative drugs.
My research described above is carried out in collaboration with Dr Susan Campbell within the BMRC and other collaborators listed below.
Dr Santosh Mordekar, Paediatric Neurologist, Sheffield Children’s NHS Foundation Trust
Dr Paul Clarke & Dr Marissa Powers, Institute of Cancer Research
Our research has been funded by the Biomolecular Sciences Research Centre at Sheffield Hallam University, The Children’s Hospital Charity, and Great Ormond Street Hospital Charity.
Publications
Journal articles
Hanson, F., Ribeiro de Oliveira, M., Cross, A., Allen, L., & Campbell, S. (2024). eIF2B localization and its regulation during the integrated stress response is cell-type specific. iScience, 27 (9). http://doi.org/10.1016/j.isci.2024.110851
Little, L.D., Barnett, S.E., Issitt, T., Bonsall, S., Carolan, V., Allen, E., ... Haywood-Small, S. (2024). Volatile Organic Compound Analysis of Malignant Pleural Mesothelioma Chorioallantoic Membrane Xenografts. Journal of breath research, 18 (4). http://doi.org/10.1088/1752-7163/ad7166
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. (pp. 13-16). http://doi.org/10.1007/8904_2013_216
Theses / Dissertations
Oliveira, M.I.R.D. (2023). The role of eIF2Bα in the integrity of eIF2B bodies. (Doctoral thesis). Supervised by Allen, L., & Campbell, S. http://doi.org/10.7190/shu-thesis-00568
Hanson, F. (2023). The Role of eIF2B Localisation in Cell-specific Stress Responses. (Doctoral thesis). Supervised by Campbell, S. http://doi.org/10.7190/shu-thesis-00555
Little, L.D. (2022). Volatile organic compounds as breathomicviomarkers of malignant mesothelioma. (Doctoral thesis). Supervised by Haywood-Small, S., Carolan, V., Allen, L., & Cole, L. http://doi.org/10.7190/shu-thesis-00495
Hodgson, R.E. (2019). eIF2B bodies and their role in the integrated stress response. (Doctoral thesis). Supervised by Campbell, S. http://doi.org/10.7190/shu-thesis-00240
Presentations
Hanson, F., Cross, A., Allen, K.E., & Campbell, S. (2022). A cell type specific role for eIF2B localisation in controlling cellular response to acute and chronic stress. Presented at: Translation UK, Sheffield Hallam University
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
Garrard, K., Campbell, S., & Allen, K.E. (2022). The role of the unfolded protein response (UPR) in childhood genetic ataxia. Presented at: Leukolabs, The University of Sheffield
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
Handley, J., Cole, L., Allen, K.E., & Campbell, S. (2022). Mass spectrometry analysis of eIF2B bodies during stress and disease. Presented at: Translation UK, Sheffield Hallam University
Campbell, S., Hanson, F., Cross, A., Allen, K.E., & Campbell, S. (2021). Differential eIF2B-mediated translation control in neuronal and glial cells. Presented at: Protein Synthesis and Translational Control, Virtual EMBL conference
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
Other activities
HCPC Partner, Registration Assessor
Postgraduate supervision
The role of eIF2Bα in the response to ISR modulation in cancer
The role of the integrated stress response (ISR) in childhood neurological disease
Previous PhD student Dr Rachel Hodgson is now a Post-Doctoral researcher at SITraN, The University of Sheffield https://www.ts-lab.co.uk/team