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Contact details +6469517587

Dr Elena Harjes PhD

Senior Lecturer in Physics

Doctoral Supervisor
School of Natural Sciences

In collaboration with Associate Professor V. Filichev, Professor G. Jameson and Professor R. Harris (University of Minnesota), we design, make and test the DNA-based inhibitors of APOBEC3 proteins.  For the biophysical characterization of the APOBEC3-inhibitors complexes, we use mainly NMR, ITC and SAXS techniques. I am also interested in dynamics of APOBEC3 proteins and their interaction with DNA and RNA substrates.

I am a NMR spectroscopist with expertise in protein and nucleic-acid structural biology. Through my scientific carrier, I have used advanced NMR techniques to connect structures and dynamics of disease-relevant proteins to their function. Area of my special interests are  double sword APOBEC proteins, which can mutate viral DNA to protect us against pathogens, but at the same time they can mutate human DNA and cause cancer development and cancer evolution as well as drug resistance in cancers. We are working to find inhibitors of those proteins to transform cancers from the terminal disease to the manageable condition

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Professional

Contact details

  • Ph: 84587
    Location: C5.05, STC
    Campus: Turitea

Qualifications

  • Doctor of Philosophy - Technical University of Dortmund (2004)

Research Expertise

Research Interests

My research focuses on protein-DNA interaction of APOBEC3 (A3) proteins. APOBEC3 proteins provide a key part of our defence against viral pathogens. They act by attacking single-stranded viral DNA (ssDNA) and destroy their genetic information by mutating the cytidines to uridines. For this defence to work, it is essential to distinguish between pathogen DNA and our own genetic information. How A3 proteins recognize specific ssDNA and specific pathogens, but neither double-stranded DNA nor RNA, remains unknown. We are using high-resolution NMR to answer this and others important biological questions.

Thematics

Health and Well-being

Area of Expertise

Field of research codes
Biochemistry and Cell Biology (060100): Biological Sciences (060000): Enzymes (060107): Structural Biology (incl. Macromolecular Modelling) (060112)

Keywords

Nuclear magnetic resonance on biomolecules

Structural Biology

Research Projects

Current Projects

Project Title: Structural basis of viral wars: Innate immune system attack on viral genomes and the counterattack by viruses.

From the dawn of humanity, war has raged between viruses and human immunity. A key first line of defence is the APOBEC3 family of enzymes, which target specific DNA-sequence motifs to mutate single-stranded viral DNA preventing replication and diseases, such as HIV-AIDS, herpes, hepatitis and more. In turn, many viruses contain genes that trick the human host into producing proteins that disable APOBEC3. HIV-1 produces protein Vif that hijacks a protein-recycling assembly to bind APOBEC3G and target it for destruction. We will determine the structural basis of this war, to address three questions: (1) How does the two-domain APOBEC3G synergistically couple these domains to target efficiently triple cytosine (-CCC-) motifs of HIV-1 and then mutate a cytosine to uracil. (2) How does viral Vif interact with human APOBEC3G to counteract destruction of its (viral) genome. (3) How does Vif interact with APOBEC3G and single-stranded DNA to permit a low level of APOBEC3G activity that HIV-1 uses to evolve fitness? Structure-elucidation of APOBEC3G-DNA, APOBEC3G-Vif and APOBEC3G-Vif-DNA complexes will use small-angle X-ray scattering techniques to provide low-resolution structures and to determine the optimum conditions for selected high-resolution structures using advanced cryogenic-electron-microscopy techniques. Our results form the basis for new anti-viral strategies.
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Date Range: 2023 - 2026

Funding Bodies: Royal Society of New Zealand; Marsden Fund - Full

Project Team:

Completed Projects

Project Title: Screening for APOBEC3B Inhibitors: New Approach to Fighting Breast Cancer

Date Range: 2014 - 2017

Funding Body: Health Research Council of New Zealand

Project Team:

Teaching and Supervision

Teaching Statement

Biophysics (parts)

Thermal Physics (parts)

Current Doctoral Supervision

Co-supervisor of:

  • Thakshila Dayananda - Doctor of Philosophy
    Investigation of Structural and Biophysical Aspects of DNA Aptamers in Binding to Complex Illicit Drugs and Utilisation of Aptamers in Biosensing Platform Development for Health and Environmental Monitoring
  • Dong Luo - Doctor of Philosophy
    Structural basis of A3G-DNA interaction for antiviral defense

Completed Doctoral Supervision

Co-supervisor of:

  • 2021 - ~ Harikrishnan Mohana Kurup - Doctor of Philosophy
    Design, Synthesis, and Evaluation of Cross-linked Single-stranded DNAs as Inhibitors of APOBEC3 Enzymes
  • 2020 - Fareeda Barzak - Doctor of Philosophy
    Biophysical and biochemical characterisation of DNA-based inhibitors of the cytosine-mutating APOBEC3 enzymes