Dr Gabriele Saretzki
Lecturer

  • Email: gabriele.saretzki@ncl.ac.uk
  • Telephone: +44 (0) 191 208 1214
  • Fax: +44 (0) 191 208 1101
  • Address: Institute for Ageing and Health, Newcastle University
    Campus for Ageing and Vitality
    Newcastle upon Tyne, NE4 5PL

Introduction

I am a cellular biologist with continuous research experience in the fields of ageing, senescence and cancer for more than 15 years. Most of my work concentrates on telomerase and oxidative stress. 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 currently use in vivo models of TERT knockout mice and dietary restriction to analyse this protective function of telomerase. We found a particular role for telomerase in brain ageing and we are currently looking into a potential role of neuronal telomerase against neurodegenerative diseases such as Alzheimers' and Parkinsons' disease.

Background

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 15 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

Qualifications

  • 1977-1982 Diploma (MSc) in Biology/Genetics, Department of Genetics and Selection, University of St. Petersburg, Russia: “Characterisation of recessive suppressor mutants depending on cyclohexamide in S. cerevisiae”(magna cum laude)
  • 1986-1990 PhD in Molecular Biology, Department of Genetics, Humboldt University Berlin, Germany: "Expression of surface antigens of Hepatitis B virus in bacteria and yeast” (magna cum laude), Supervisor Prof. T. Bőrner
  • 1994-1995 Postdoctoral Research Fellowship, Institute of Pathology of the Technical University and Research Institute (GSF), Munich, Germany
  • 7-9/1996 Research Fellow/ Visiting Scientist, Geron Corp. Menlo Park, CA, USA

Previous Positions

  • 1982-86 Junior Research Associate, Department of Genetics, Humboldt-University Berlin, Germany
  • 1986-1989 PhD student, Department of Genetics, Humboldt- University Berlin, Germany
  • 1989-99 Research Associate, Institute of Pathology, Charite’, Humboldt-University Berlin
  • 1999-2000 Research Associate, Department of Gynecology, University Hospital, Freiburg, Germany
  • 2001-2002 Senior Research Associate, Gerontology, Institute for Ageing and Health, University of Newcastle, U.K.
  • 2002-presentLecturer, Crucible Lab, Institute for Ageing and Health, Newcastle University, U.K.

Memberships

British Society for Reserach into Ageing (BSRA), Biochemical Society, German Society for Ageing Reserach (DGFA)

Honours and Awards

•1994-1995 Research Fellowship Jung-Foundation for Science, Hamburg, Germany
•1996 (3 month) Research Fellowship Geron Corp. Menlo Park, CA

Languages

German, English, Russian, 

Informal Interests

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.

Research Interests

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 hypothesis that this could protect neurons from oxidative damage. We use embryonic mouse neurons from telomerase/TERT deficient as well as wild type mice to find out whether telomerase protein protects neurons against agents such as hyperphosphorylated tau protein which induces neurodegeneration in the context of Alzheimer's disease and othet tauopaties.

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. 

Other Expertise

•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 am currently introducing new methods for measuring cognitive properties such as Barnes maze (learning and memory) and locomotor tests for mice in our institute. 

 
Current Work

I am shifting my focus now to the analysis of possible role of telomerase/TERT in the brain and for brain ageing as well as for the development of neurodegenerative diseases.

I am using human brain material from the NBTR as well as using a TERT knockout mouse model. We are cultivating mouse neurons as in vitro models and are interested in the influence of non-telomeric functions of TERT on mitochondrial properties and oxidative stress parameters.

Future Research

I have various ongoing research collaborations, including work on human embryonic and adult stem cells, as well as iPS cells.

I have a collaborationwith investigators in the field of Alzheimers' research from our institute  in a Dunhill Medical Trust funded Serendipity project where we investigate the involvement of oxidative stress and mitochondrial dysfuntion and a possible protective role of telomerase/TERT in the disease.

Research Roles

I am a PI and Lecturer in Ageing Research at the Institute for Ageing and Health.

Postgraduate Supervision

I have currently 1 RA, 2 PhD students and 2 masters 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.

Esteem Indicators

speaker and session chair for various national and international meetings on Ageing etc

Funding

Completed:

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

Active:

2012-2013: Dunhill Medical Trust Srendipity award on the role of mitochondrial Telomerase in the protection from tau related neurodegeneration (76.5K)

Patents

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
356

Projects

Undergraduate Teaching

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 

Postgraduate Teaching

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"