School of Natural Sciences staff

Dr Elena Harjes staff profile picture

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

Summary of Research Projects

Position Current Completed
Project Leader 3 7
Team Member 1 2

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:

Research Outputs

Journal

Harjes, S., Kurup, HM., Rieffer, AE., Bayarjargal, M., Filitcheva, J., Su, Y., . . . Jameson, GB. (2023). Structure-guided inhibition of the cancer DNA-mutating enzyme APOBEC3A. Nature Communications. 14(1)
[Journal article]Authored by: Filichev, V., Harjes, E., Jameson, G., Kurup, H.
Harjes, E., Edwards, PJB., Bisset, SW., Patchett, ML., Jameson, GB., Yang, SH., . . . Norris, GE. (2023). NMR Shows Why a Small Chemical Change Almost Abolishes the Antimicrobial Activity of Glycocin F. Biochemistry. 62(17), 2669-2676
[Journal article]Authored by: Edwards, P., Harjes, E., Jameson, G.
Kurup, HM., Kvach, MV., Harjes, S., Jameson, GB., Harjes, E., & Filichev, VV. (2023). Seven-membered ring nucleobases as inhibitors of human cytidine deaminase and APOBEC3A. Organic and Biomolecular Chemistry. 21(24), 5117-5128
[Journal article]Authored by: Filichev, V., Harjes, E., Jameson, G., Kurup, H.
Harjes, S., Kurup, HM., Rieffer, AE., Bayaijargal, M., Filitcheva, J., Su, Y., . . . Jameson, GB. (2023). Structure-guided inhibition of the cancer DNA-mutating enzyme APOBEC3A.. bioRxiv.
[Journal article]Authored by: Filichev, V., Harjes, E., Jameson, G., Kurup, H.
Kurup, HM., Kvach, MV., Harjes, S., Barzak, FM., Jameson, GB., Harjes, E., . . . Filichev, VV. (2022). Design, Synthesis, and Evaluation of a Cross-Linked Oligonucleotide as the First Nanomolar Inhibitor of APOBEC3A. Biochemistry. 61(22), 2568-2578
[Journal article]Authored by: Filichev, V., Harjes, E., Jameson, G., Kurup, H.
Barzak, FM., Ryan, TM., Mohammadzadeh, N., Harjes, S., Kvach, MV., Kurup, HM., . . . Jameson, GB. (2022). Small-Angle X-ray Scattering (SAXS) Measurements of APOBEC3G Provide Structural Basis for Binding of Single-Stranded DNA and Processivity. Viruses. 14(9)
[Journal article]Authored by: Filichev, V., Harjes, E., Jameson, G., Kurup, H.
Barzak, FM., Ryan, TM., Kvach, MV., Kurup, HM., Aihara, H., Harris, RS., . . . Jameson, GB. (2021). Small-angle x-ray scattering models of apobec3b catalytic domain in a complex with a single-stranded dna inhibitor. Viruses. 13(2)
[Journal article]Authored by: Filichev, V., Harjes, E., Jameson, G., Kurup, H.
Varnava, KG., Edwards, PJB., Cameron, AJ., Harjes, E., & Sarojini, V. (2021). Cyclic peptides bearing the d-Phe-2-Abz turn motif: Structural characterization and antimicrobial potential. Journal of Peptide Science. 27(2)
[Journal article]Authored by: Edwards, P., Harjes, E.
Harjes, E., Jameson, GB., Tu, YH., Burr, N., Loo, TS., Goroncy, AK., . . . Norris, GE. (2021). Experimentally based structural model of Yih1 provides insight into its function in controlling the key translational regulator Gcn2. FEBS Letters. 595(3), 324-340
[Journal article]Authored by: Edwards, P., Harjes, E., Jameson, G., Loo, T., Sattlegger, E.
Kvach, MV., Barzak, FM., Harjes, S., Schares, HAM., Kurup, HM., Jones, KF., . . . Filichev, VV. (2020). Differential Inhibition of APOBEC3 DNA-Mutator Isozymes by Fluoro- and Non-Fluoro-Substituted 2′-Deoxyzebularine Embedded in Single-Stranded DNA. ChemBioChem. 21(7), 1028-1035
[Journal article]Authored by: Filichev, V., Harjes, E., Jameson, G., Kurup, H.
Barzak, FM., Harjes, S., Kvach, MV., Kurup, HM., Jameson, GB., Filichev, VV., . . . Harjes, E. (2019). Selective inhibition of APOBEC3 enzymes by single-stranded DNAs containing 2′-deoxyzebularine. Organic and Biomolecular Chemistry. 17(43), 9435-9441
[Journal article]Authored by: Filichev, V., Harjes, E., Jameson, G., Kurup, H.
Kvach, MV., Barzak, FM., Harjes, S., Schares, HAM., Jameson, GB., Ayoub, AM., . . . Harjes, E. (2019). Inhibiting APOBEC3 Activity with Single-Stranded DNA Containing 2′-Deoxyzebularine Analogues. Biochemistry. 58(5), 391-400
[Journal article]Authored by: Filichev, V., Harjes, E., Jameson, G.
Cameron, AJ., Varnava, KG., Edwards, PJB., Harjes, E., & Sarojini, V. (2018). Acyclic peptides incorporating the d-Phe-2-Abz turn motif: Investigations on antimicrobial activity and propensity to adopt β-hairpin conformations. Journal of Peptide Science. 24(8-9)
[Journal article]Authored by: Edwards, P., Harjes, E.
Cameron, AJ., Edwards, PJB., Harjes, E., & Sarojini, V. (2017). Tyrocidine A Analogues Bearing the Planar d-Phe-2-Abz Turn Motif: How Conformation Impacts Bioactivity. Journal of Medicinal Chemistry. 60(23), 9565-9574
[Journal article]Authored by: Edwards, P., Harjes, E.
Cameron, AJ., Squire, CJ., Edwards, PJB., Harjes, E., & Sarojini, V. (2017). Crystal and NMR Structures of a Peptidomimetic β-Turn That Provides Facile Synthesis of 13-Membered Cyclic Tetrapeptides. Chemistry - An Asian Journal. 12(24), 3195-3202
[Journal article]Authored by: Edwards, P., Harjes, E.
Harjes, S., Jameson, GB., Filichev, VV., Edwards, PJB., & Harjes, E. (2017). NMR-based method of small changes reveals how DNA mutator APOBEC3A interacts with its single-stranded DNA substrate. Nucleic Acids Research. 45(9), 5602-5613
[Journal article]Authored by: Edwards, P., Filichev, V., Harjes, E., Jameson, G.
Harjes, S., Solomon, WC., Li, M., Chen, KM., Harjes, E., Harris, RS., . . . Matsuo, H. (2013). Impact of H216 on the DNA binding and catalytic activities of the HIV restriction factor APOBEC3G. Journal of Virology. 87(12), 7008-7014
[Journal article]Authored by: Harjes, E.
Albin, JS., Anderson, JS., Johnson, JR., Harjes, E., Matsuo, H., Krogan, NJ., . . . Harris, RS. (2013). Dispersed sites of HIV Vif-dependent polyubiquitination in the DNA deaminase APOBEC3F. Journal of Molecular Biology. 425(7), 1172-1182
[Journal article]Authored by: Harjes, E.
Shindo, K., Li, M., Gross, PJ., Brown, WL., Harjes, E., Lu, Y., . . . Harris, RS. (2012). A comparison of two single-stranded DNA binding models by mutational analysis of APOBEC3G. Biology. 1(2), 260-276
[Journal article]Authored by: Harjes, E.
Harjes, E., Kitamura, A., Zhao, W., Morais, MC., Jardine, PJ., Grimes, S., . . . Matsuo, H. (2012). Structure of the RNA claw of the DNA packaging motor of bacteriophage φ29. Nucleic Acids Research. 40(19), 9953-9963
[Journal article]Authored by: Harjes, E.
Dang, Y., Abudu, A., Son, SM., Harjes, E., Spearman, P., Matsuo, H., . . . Zheng, YH. (2011). Identification of a single amino acid required for APOBEC3 antiretroviral cytidine deaminase activity. Journal of Virology. 85(11), 5691-5695
[Journal article]Authored by: Harjes, E.
Albin, JS., LaRue, RS., Weaver, JA., Brown, WL., Shindo, K., Harjes, E., . . . Harris, RS. (2010). A single amino acid in human APOBEC3F alters susceptibility to HIV-1 Vif. Journal of Biological Chemistry. 285(52), 40785-40792
[Journal article]Authored by: Harjes, E.
Shandilya, SMD., Nalam, MNL., Nalivaika, EA., Gross, PJ., Valesano, JC., Shindo, K., . . . Schiffer, CA. (2010). Crystal Structure of the APOBEC3G Catalytic Domain Reveals Potential Oligomerization Interfaces. Structure. 18(1), 28-38
[Journal article]Authored by: Harjes, E.
Harjes, E., Gross, PJ., Chen, KM., Lu, Y., Shindo, K., Nowarski, R., . . . Matsuo, H. (2009). An Extended Structure of the APOBEC3G Catalytic Domain Suggests a Unique Holoenzyme Model. Journal of Molecular Biology. 389(5), 819-832
[Journal article]Authored by: Harjes, E.
Chen, KM., Harjes, E., Gross, PJ., Fahmy, A., Lu, Y., Shindo, K., . . . Matsuo, H. (2008). Structure of the DNA deaminase domain of the HIV-1 restriction factor APOBEC3G. Nature. 452(7183), 116-119
[Journal article]Authored by: Harjes, E.
Harjes, E., Harjes, S., Wohlgemuth, S., Müller, KH., Krieger, E., Herrmann, C., . . . Bayer, P. (2006). GTP-Ras Disrupts the Intramolecular Complex of C1 and RA Domains of Nore1. Structure. 14(5), 881-888
[Journal article]Authored by: Harjes, E.
Bayer, E., Goettsch, S., Mueller, JW., Griewel, B., Guiberman, E., Mayr, LM., . . . Bayer, P. (2003). Structural analysis of the mitotic regulator hPin1 in solution: Insights into domain architecture and substrate binding. Journal of Biological Chemistry. 278(28), 26183-26193
[Journal article]Authored by: Harjes, E.
Bayer, E., Goettsch, S., Mueller, JW., Griewel, B., Guiberman, E., Mayr, LM., . . . Bayer, P. (2003). Structural Analysis of the Mitotic Regulator hPin1 in Solution: INSIGHTS INTO DOMAIN ARCHITECTURE AND SUBSTRATE BINDING. Journal of Biological Chemistry. 278(28), 26183-26193
[Journal article]Authored by: Harjes, E.

IP

Kurup, H., Filichev, VV., Harjes, E., Harjes, S., Jameson, G., Kvach, M., . . . Su, Y.(2022). . WO2022162536: SINGLE STRANDED DNA ENZYME INHIBITORS
[Patent]Authored by: Filichev, V., Harjes, E., Jameson, G., Kurup, H.Contributed to by: Kurup, H.

Conference

Sattlegger, E., Harjes, E., Jameson, G., Tu, J., Burr, N., Loo, T., . . . Norris, G. (2018). Deciphering intramolecular interactions in Yih1, a negative regulator of the protein kinase Gcn2.. Poster session presented at the meeting of Translational Control Meeting,Cold Spring Harbor, NY, USA
[Conference Poster]Authored by: Edwards, P., Harjes, E., Jameson, G., Loo, T., Sattlegger, E.
Filichev, VV., Harjes, S., Barzak, F., Kvach, MV., Jameson, GB., & Harris, RS. (2017). Modulating APOBEC deaminase activity with ssDNA containing zebularine. , 7th Cambridge Symposium on Nucleic Acids Chemistry and Biology
[Conference Abstract]Authored by: Filichev, V., Harjes, E., Jameson, G.
Harjes, E., Harjes, S., Filichev, V., Jameson, GB., & Edwards, P.(2016, October). How DNA mutating enzymes interact with their DNA substrates. .
[Conference]Authored by: Edwards, P., Filichev, V., Harjes, E., Jameson, G.
Edwards, PJ., Munro, B., Brox, T., Galvosas, P., Dykstra, R., Harjes, E., . . . Williams, MAK. (2015). The effect of shear-induced reorientation of a bacteriophage nematic phase on the measurement of residual dipolar couplings. Poster session presented at the meeting of ANZMAG Conference. Bay of Islands, New Zealand
[Conference Poster]Authored by: Edwards, P., Harjes, E.
Harjes, E. (2015, November). Structure and DNA interaction of double-edged swords APOBEC3 proteins. Presented at The Australian and New Zealand Magnetic Resonance Society. Bay of Islands, New Zealand.
[Conference Oral Presentation]Authored by: Harjes, E.
Harjes, E., & Matsuo, H. (2014, June). Functional insights from protein and RNA structures. New Zealand Structural Biology meeting. Presented at New Zealand Structural Biology meeting
[Conference Oral Presentation]Authored by: Harjes, E.
Harjes, E., & Matsuo, H.(2014, June). Functional insights from protein and RNA structures. . (pp. 8 - 8).
[Conference]Authored by: Harjes, E.
Sattlegger, E., Jameson, GB., Norris, GE., Burr, N., Loo, TS., Goroncy, A., . . . Harjes, E. (2014). Reconciling synchotron SAXS Data with NMR data for a two-domain protein.. (pp. 57 - 58). , The Australian Synchrotron Users Meeting
[Conference Abstract]Authored by: Harjes, E., Jameson, G., Loo, T., Sattlegger, E.
Jameson, GB., Norris, GE., Burr, N., Loo, TS., Goroncy, A., Sattlegger, E., . . . Harjes, E. (2014). Reconciling synchotron SAXS data with NMR data for a two-domain protein. Poster session presented at the meeting of The Australian Synchrotron Users Meeting 2014. Melbourne, Australia
[Conference Poster]Authored by: Harjes, E., Jameson, G., Loo, T., Sattlegger, E.
Harjes, E., & Matsuo, H. (2013, September). Structure of the RNA claw of the DNA packaging motor of bacteriophage Phi29. Presented at New Zealand Institute of Physics Conference. Nelson, New Zealand.
[Conference Oral Presentation]Authored by: Harjes, E.
Harjes, E., & Matsuo, H.(2013, June). Structure of the RNA claw of the DNA packaging motor of bacteriophage Phi29.. .
[Conference]Authored by: Harjes, E.

Teaching and Supervision

Teaching Statement

Biophysics (parts)

Thermal Physics (parts)

Summary of Doctoral Supervision

Position Current Completed
Main Supervisor 1 0
Co-supervisor 1 2

Current Doctoral Supervision

Main Supervisor of:

  • Dong Luo - Doctor of Philosophy
    Structural basis of A3G-DNA interaction for antiviral defense

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

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