I am a cellular biologist with research experience in the fields of ageing, senescence and cancer for more than 20 years. Most of my work focuses on telomerase/TERT and oxidative stress as well as DNA damage. I am interested in the role of oxidative stress and mitochondria in the ageing process and cellular senescence. My group has shown a protective role for telomerase/TERT for mitochondrial function and decrease of oxidative stress in various in vitro systems (Ahmed et al., 2008, Singhapol et al., 2013). We recently demonstrated a potential protective role of neuronal TERT moving into mitochondria in neurodegenerative diseases on brains from patients with Alzheimers' disease (Spilsbury et al., 2015). We also used in vivo models of TERT knockout mice under dietary restriction and rapamycin treatment as well as for transduction of mutated tau to analyse this protective function of telomerase/TERT in mitochondria and found a role for mitochondrial TERT in brain ageing and neurodegenerative diseases in vivo.
I am a cellular biologist with a broad range of experience, interests and technical skills. My main scientific career has been devoted to investigating the involvement of oxidative stress, telomeres and telomerase in processes connected to cellular ageing, cancer, stem cells as well as more recently, brain ageing. For my doctoral research, I worked in molecular virology, expressing surface domains of the hepatitis B virus in different microorganisms for application as vaccines against Hepatitis B. During that time I prepared and taught a half year laboratory course in general and molecular genetics. For my first post-doc years I worked in diagnostic pathology, introducing new methods like in-situ hybridization, immunohistochemistry and PCR into pathological diagnostics. In the context of cancer pathology, I analysed translocations ,microsatellite instabilities, losses of heterozygosity [3, 9] and gene amplifications .
For the last 20 years my main research interests have been devoted to the role of oxidative stress, telomeres and telomerase in ageing, cancer and stem cells. In close collaboration with other scientists I have investigated the role of senescence, oxidative stress and telomeres in the basic biology of ageing as well as related clinical questions. Our current findings about a potential role of non-canonical telomerase functions of the telomerase protein TERT in mitochondria of brain during dietary restriction (DR) and rapamycin treatment got me into the area of brain ageing and neurodegenerative diseases where I closely collaborate with neuropathologists in our Institute.
Roles and Responsibilities
•Editorial member of “Biogerontology” from 2002-2012, Associated Editor for BMC Biology since 2009, Oxidative Medicine and Longevity as well as PLoS one since 2011
•Member of the Executive Committee of the British Society for Reserach into Ageing (BSRA) 2009-2012
•Member of NESCI (North East Stem Cell Institute), Associate member of the Institute for Genetics Medicine and the Northern Institute for Cancer Research (NICR)
•Reviewer for different funding bodies (BBSRC, Wellcome, MRC, Singapore Medical Academy etc) and various journals:Mechanism of Aging and Development, Ageing Cell, Experimental Gerontology,Biogerontology,Experimental Cell Research,International Journal of Cancer,Molecular Cancer,Reviews in Medical Chemistry, Cancer Letters, PLos one, BMC, NAR etc
British Society for Reserach into Ageing (BSRA), Biochemical Society, German Society for Ageing Reserach (DGFA)
•1994-1995 Research Fellowship Jung-Foundation for Science, Hamburg, Germany
•1996 (3 month) Research Fellowship Geron Corp. Menlo Park, CA
German, English, Russian,
I love cats and animals, I support WWF, Animal Asia and the RSPCA, I am interested in environmental issues, I like sports (windsurfing, climbing, dancing) and travelling.
My research interests are devoted to the role of telomerase in ageing and cancer and under oxidative stress. I focus particularly on non-telomeric and non-canonical roles of telomerase. We and others have found that telomerase shuttles from the nucleus to mitochondria under oxidative stress. My group was the first to describe a protective role of telomerase and its protein part TERT onto mitochondria (Ahmed et al., 2008). We recently found that cancer cells protect themselfs from external stress by mitochondrial localisation of telomerase which decreases nuclear damage and apoptosis and is therefore a pro-survival mechanism (Singhapol et al., 2013). Since adult neurons do not express telomerase activity but still express TERT, the protein part of telomerase, we demonstrated recently that this could protect neurons from oxidative damage and neurodegenerative agents such as hyperphosphorylated tau (Spilsbury et al., 2015). We also used embryonic mouse neurons from telomerase/TERT deficient as well as wild type mice and transduced them with lentiviruses against a mutant (P301L) tau protein and showed more oxidative stress and lipid peroxidation in neurons lacking TERT compared to wild type neurons (Spilsbury et al., 2015). Thus TERT seems to protects neurons against hyperphosphorylated tau protein which induces neurodegeneration in the context of Alzheimer's disease and other tauopaties. We propose that boosting TERT levels in the brain using known telomerase activators could help prevent or ameliorate neurodegenerative diseases and dementia related to it. I have introduced new methods for measuring cognitive properties such as Barnes maze (learning and memory) and locomotor tests for mice in our institute.
I am also interested in the mechanisms of stem cell ageing and senescence and investigate the role of telomeres, telomerase and oxidative stress in those. I recently got interested and involved in nutritional aspects of ageing.
•regular reviews for different funding bodies (UK: BBSRC, Wellcome, MRC, Singapore Medical academy).
•Reviewer for different journals: PLoS one, Mechanism of Aging and Development,
Ageing Cell, Experimental Gerontology, Biogerontology, Experimental Cell Research, International Journal of Cancer, Molecular Cancer, Cancer Letters
I have various ongoing research collaborations, including work on human iPS cells and nutritional aspects analysing fat and differentiation adipocytes in vitro which we treat with lipidogenic media and test nutritional foof components such as nitrate and chicoric acid for their beneficial effects with the aim of uncovering the underlying mechanisms..
I am a PI and Lecturer in Ageing Research at the Institute for Cell and Molecular Biosciences and a member of the Newcastle Institute for Ageing.
I have currently 2 PhD students. In addition, I have regular national and international undergraduate and graduate students and scientists who work in placements, masters, undergraduate projects and summer student projects and perform scientific visits to my lab.
speaker and session chair for various national and international meetings on Ageing etc
1997-2000, Cancer Society Berlin: Telomerase combination therapy £200k
•1988-1999 Humboldt University Berlin, Medical Faculty (Charite) Research fund: “Diagnostic potential of telomerase activity for early stages of cervical intraepithelial lesions”, £10k
•2001-2003 Medical Research Council, U.K.: “Telomerase inhibition in prostate cancer” (part of Cooperative Grant on Prostate Cancer) 1/02 - 12/03, £140k
•2003-2004: National Health Trust (Special Trustees): “Mechanism of fast apoptosis induction by targeting telomerase with an anti-hTERT ribozyme in human cancer cells”, £30K
•2003-2008 Co- Investigator for Research into Ageing (now Age UK) Programme “Human cell replicative senescence as stress response: Role of telomeres” , £398K
•2005-2010 named researcher on BBSRC Grant Centre for Integrated Systems Biology of Ageing and Nutrition (CISBAN) for Biogerontology, Institute for Ageing and Health, School of Clinical medical Sciences, University Newcastle, £6.7million
•2005-2006 Co-Investigator for Grant of the National Health Trust (Special Trustees): “The Role of Oxidative Stress in the Phenotypic and Functional Change Occurring in Lung Epithelial Cells undergoing Epithelial to Mesenchymal Transition (EMT)”, £50K
•2005-2008 Co-Investigator for Cancer UK studentship “Identification and validation of candidate genes involved in differentiation of human prostate epithelial stem cells” £70k
2008-2009: co-applicant : X-ray research irradiation system, Ref BB/F010966/1, £141849.91, BBSRC,
2009-2011, co-applicant on grant from "Wellbeing of women", The role of the identified regulators of cell fate (RCF) and metastasis inducing proteins (MIP) in endometrial stem/progenitor cells (SPC) in endometriosis. £149K
2009-2012, co-applicant with Prof. Majlinda Lako “Investigating early haematopoietic development in ligase IV and XLF patients using induced pluripotent stem cells”. £165.845, Leukaemia Research Fund.
2008-2012, PhD studentship, £78K from Thai government
2009-2012 PhD studentship, 50K, BBSRC
2010-2013, PhD studentship, 50K from Biomedical Research Centre at Newcastle University
2012-2013: Dunhill Medical Trust Srendipity award on the role of mitochondrial Telomerase in the protection from tau related neurodegeneration (76.5K)
1-6/2015: MRC confidence in concept funding (13.5K) for testing beneficial effects on pathology and brain function in PD line D mice using telomerase activators.
von Zglinicki T, Ludwig A, Saretzki G “Ribozymes targeting the catalytic subunit of human telomerase (hTERT)”, German Patent # 199 03 961.5, International patent PCT/DE 100 03
1984-89 Mentor for undergraduates in molecular biology, Institute of Biology, Humboldt-University Berlin
1984-1985 Conception and teaching of a laboratory course “Molecular Genetics” for undergraduate students in Biology
1985-87 Lectures in Molecular Biology, Institute of Biology, Humboldt-University Berlin
since 2003- regular project supervisor for undergraduate stage 3 projects
since 2010- teaching in the new undergraduate model "Biology of Ageing"
Annual supervision of summer students
1993-1999 Supervision of MSc, PhD and MD students, Institute of Pathology, Humboldt-University Berlin
1996 - 1999 Lectures series “ Molecular Medicine and Tumours” , Institute of Pathology, Charite’, Humboldt-University Berlin
since 2001: Supervision of 10 graduate students and projects, at the Institute for Ageing and Health, Newcastle University, supervision of masters, MRES and MPHIL students
since 2009-teaching in the MRes course "Ageing" at Newcastle University
since 2011: teaching in masters course "Stem cells and regenerative medicine"