An esteemed scientist and Chief Scientific Officer with the Metropolitan Police, Maria became an Honorary Professor at the University of Warwick in 2023. Here she runs her personal research that includes both basic and applied biomedical projects such as vesicle generation and translocation mechanisms in response to environmental cues and virus- and drug-induced cellular remodelling pathways. From 2012- 2024 Maria progressed from beamline scientist to a principal beamline scientist at Diamond Light Source, Harwell Campus, Oxford, working on 3D correlative imaging of biological systems. She was responsible for the design, installation and commissioning of high-resolution 3D microscopes for biological samples under cryogenic conditions. Whilst at Diamond, Maria delivered a successful correlative imaging synchrotron beamline and associated technique platform and headed up a team of scientists looking to better understand host-pathogen interactions at the cellular level. Previously, she was a Principal Investigator at the Structural Biology Laboratory at the Nuffield Department of Clinical Medicine of the University of Oxford and prior to that a post-doctoral researcher with Cancer Research UK. Maria undertook her graduate studies at the University of York, under the supervision of Professors K. Wilson and E. Dodson.
Biography
2023-present Honorary Professor, Department of Chemistry, University of Warwick
2008-2012 Royal Society Dorothy Hodgkin Fellow/Principal investigator, Structural Immunology, Division of Structural Biology, University of Oxford.
2007-2008 Post-doctoral Research Fellow, Division of Structural Biology, University of Oxford
2005-2007 EMBO Postdoctoral Research Fellow, Division of Structural Biology, University of Oxford
2002-2005 CRUK Postdoctoral Fellow, Weatherall Institute of Molecular Medicine, University of Oxford
July 2002 Ph.D in Chemistry, University of York (Supervisors: Prof. Keith S Wilson, Prof. Eleanor J Dodson (FRS))
I have an extensive network of collaborators (national and international from academia and industry) and a personal research portfolio that focuses on:
(b) structural cell biology and morphogenesis pathways and
(c) understanding host pathogen-interactions at the cellular and molecular level with an emphasis on viral escape and clearance pathways.
Peer-reviewed research publications
1.K Nahas, V Connor, KM Scherer, CF Kaminski, M Harkiolaki*, CM Crump, SC Graham Near-native state imaging by cryo-soft-X-ray tomography reveals remodelling of multiple cellular organelles during HSV-1 infection. PloS Pathog 2022; 18 (7): e1010629.
https://doi.org/10.1371/journal.ppat.1010629
2.K Nahas, J Ferreira-Fernandes, N Vyas, CM Crump, SC Graham, M Harkiolaki*. Contour : A semi-automated segmentation and quantitation tool for cryo-soft-X-ray tomography. Biological Imaging 2022; 2: E3.
https://doi.org/10.1017/S2633903X22000046
3.P Pymm, S Tenzer, E Wee, M Weimershaus, A Burgevin, S Kollnberger, J Gerstoft, TM Josephs, K Ladell, JE McLaren, V Appay, DA Price, L Fugger, JI Bell, H Schild, P van Endert, M Harkiolaki, AKN Iversen. Epitope length variants balance protective immune responses and viral escape in HIV-1 infection. Cell Rep. 2022; 38(9):110449.
https://doi.org/10.1016/j.celrep.2022.110449
4.HF Chang, C Schirra, M Ninov, U Hahn, K Ravichandran, E Krause, U Becherer, Š Bálint, M Harkiolaki, H Urlaub, S Valitutt, CT Baldari, ML Dustin, R Jahn, J Rettig. Identification of distinct cytotoxic granules as the origin of supramolecular attack particles in T lymphocytes. Nat Commun. 2022; 13(1):1029.
https://doi.org/10.1038/s41467-022-28596-y
5.Groen J, A Palanca, A Aires, JJ Conesa, D Maestro, S Rehbein, M Harkiolaki, AV Villar, AL Cortajarena, E Pereiro. Correlative 3D cryo X-ray imaging reveals intracellular location and effect of designed antifibrotic protein-nanomaterial hybrids. Chem. Sci. 2021; 12(45):15090-15103.
https://doi.org/10.1039/d1sc04183e
6.M Koronfel, I Kounatidis, DM Mwangangi, N Vyas, C Okolo,AJadhav, T Fish, P Chotchuang, A Schulte, RC Robinson, M Harkiolaki M*. Correlative cryo-imaging of the cellular universe with soft X-rays and laser light used to track F-actin structures in mammalian cells. Acta. Crystallogr. D Struct. Biol. 2021; 77(Pt 12):1479-1485.
https://doi.org/10.1107/S2059798321010329
7.P Phillips, JM Parkhurst, I Kounatidis, C Okolo, TM Fish, JH Naismith, MA Walsh, M Harkiolaki*, M Dumoux. Single cell cryo-Soft X-ray tomography shows that each Chlamydia Trachomatis inclusion is a unique community of bacteria. Life. 2021; 11(8), 842.
https://doi.org/10.3390/life11080842
8.L Mendonca, A Howe, JB Gilchrist, D Sun, M Knight, LC Zanetti-Domingues, B Bateman, AS Krebs, L Chen, J Radecke, Y Sheng, VD Li, T Ni, I Kounatidis, MA Koronfel, M Szynkiewicz, M Harkiolaki, M L Martin-Fernandez, W James, P Zhang. Correlative multi-scale cryo-imaging unveils SARS-CoV-2 assembly and egress. Nature Commun. 2021; 12:4629.
https://doi.org/10.1038/s41467-021-24887-y
9.N Vyas, N Perry N, CA Okolo, I Kounatidis, TM Fish, KL Nahas, A Jadhav, MA Koronfel, J Groen, E Pereiro, IM Dobbie, M Harkiolaki*. Cryo-structured illumination microscopic data collection from cryogenically preserved cells.J. Vis. Exp. 2021; 171:e62274.
https://doi.org/10.3791/62274
10.N Vyas, S Kunne, TM Fish, IM Dobbie, M Harkiolaki*, P Paul-Gilloteaux. Protocol for image registration of correlative soft x-ray tomography and super-resolution structured illumination microscopy images. STAR Protoc. 2021; 2(2): 100529.
https://doi.org/10.1016/j.xpro.2021.100529
11.CA Okolo, I Kounatidis, J. Groen, KL Nahas, S Balint, TM Fish, MA Koronfel, AL Cortajarena, IM Dobbie, E Pereiro, M Harkiolaki*. Sample preparation strategies for efficient correlation of 3D SIM and soft X-ray tomography data at cryogenic temperatures. Nature Protoc. 2021; 16(6):2851-2885.
https://doi.org/10.1038/s41596-021-00522-4
12.J Groen, A Sorrentino, L Aballe, R Oliete, R Valcárcel, C Okolo, I Kounatidis, M Harkiolaki, AJ Pérez-Berná, E Pereiro. A 3D cartographic description of the cell by cryo soft x-ray tomography. J. Vis. Exp. 2021; 169:e62190.
https://doi.org/10.3791/62190
13.A Iudin, U Sarkans, MA Koronfel, T Fish, I Dobbie, M Harkiolaki, A Patwardhan, GJ Kleywegt. Data-deposition protocols for correlative soft X-ray tomography and super-resolution structured illumination microscopy applications.STAR Protoc. 2021; 2(1):100253.
https://doi.org/10.1016/j.xpro.2020.100253
14.CA Okolo, A Jadhav, P Philips, M Dumoux, AA McMurray, VD Joshi, C Pizzey, M Harkiolaki*. Correlative imaging using super-resolution fluorescence microscopy and soft X-ray tomography at cryogenic temperatures provides a new way to assess virosome solutions for vaccine development. J. Microsc. 2021; 284(3):214-232.
https://doi.org/10.1111/jmi.13054
15.U Sarkans, W Chiu, L Collinson, MC Darrow, J Ellenberg, D Grunwald, JK Hériché, A Iudin, GG Martins, T Meehan, K Narayan, A Patwardhan, MRG Russell, HR Saibil, C Strambio-De-Castillia, JR Swedlow, C Tischer, V Uhlmann, P Verkade, M Barlow, O Bayraktar, E Birney, C Catavitello, C Cawthorne, S Wagner-Conrad, E Duke, P Paul-Gilloteaux, E Gustin, M Harkiolaki, P Kankaanpä, T Lemberger, J McEntyre, Moore J, Nicholls AW, Onami S, Parkinson H, Parsons M, Romanchikova M, Sofroniew N, J Swoger, N Utz, LM Voortman, F Wong, P Zhang, GJ Kleywegt, A Brazma. REMBI: Recommended Metadata for Biological Images-enabling reuse of microscopy data in biology.Nat Methods. 2021; 18: 1418-1422.
https://doi.org/10.1038/s41592-021-01166-8
16.EM Bolitho, C Sanchez-Cano, Huayun Shi, PD Quinnn, M Harkiolaki*, C Imberti, PJ Sadler. Single cell chemistry of photoactivatable platinum anticancer complexes. J. Am. Chem. Soc. 2021; 143:20224-20240.
https://doi.org/10.1021/jacs.1c08630
17.M Koronfel, I Kounatidis, DM Mwangangi, N Vyas, C Okolo, A Jadhav, T Fish, P Chotchuang, A Schulte, RC Robinson, M Harkiolaki*. Correlative cryo-imaging of the cellular universe with soft x-rays and laser light used to track F-actin structures in mammalian cells. Acta Crystallogr D Biol Crystallogr. 2021; 77: 1479-1485.
https://doi.org/10.1107/S2059798321010329
18.I Kounatidis, ML Stanifer, MA Philips, P Paul-Giloteaux, X Heiligenstein, H Wang, CA Okolo, TM Fish, MC Spink, DI Stuart, I Davis, S Boulant, JM Grimes, IM Dobbie, M Harkiolaki*. 3D Correlative cryo-structured illumination fluorescence and soft X-ray microscopy elucidates reovirus intracellular release pathway. Cell. 2020; 182(3); 515-530.e17.
https://doi.org/10.1016/j.cell.2020.05.051
19.MA Phillips, M Harkiolaki, DMS Pinto, RM Parton, A Palanca, M Garcia-Moreno, I Kounatidis, JW Sedat, DI Stuart, A Castello, MJ Booth, I Davis, IM Dobbie. CryoSIM: super- resolution 3D structured illumination cryogenic fluorescence microscopy for correlated ultrastructural imaging.Optica. 2020; 7(7): 802-812.
https://doi.org/10.1364/OPTICA.393203
20.EM Bolitho, C Sanchez-Cano, H Huang, I Hands-Portman, M Spink, PD Quinn, M Harkiolaki*, PJ Sadler. X-ray tomography of cryopreserved human prostate cancer cells: mitochondrial targeting by an organoiridium photosensitiser.J. Biol. Inorg. Chem. 2020; 25(2):295-303. 020) 25:295–303
https://doi.org/10.1007/s00775-020-01761-8
21.Š Bálint, S Müller, R Fischer, BM Kessler, M Harkiolaki, S Valitutti, ML Dustin. Supramolecular attack particles are autonomous killing entities released from cytotoxic T cells.Science. 2020; 22;368(6493):897-901.
https://doi.org/10.1126/science.aay9207
22.M Hand, H Wang, M Harkiolaki, F Venturini, R Arrigo, P Ferrer-Escorihuela, S Alcock, I Nistea, A Marshall, S Scott, L Duke, H Georg, K Sawhney. Compensation of x-ray mirror distortion by cooling temperature control.AIP Conf. Proc. 2019;p 060044.
23.F Vaz, I Kounatidis, G Covas, RM Parton, M Harkiolaki, I Davis, SR Filipe, P Ligoxygakis. Accessibility to Peptidoglycan Is Important for the Recognition of Gram-Positive Bacteria in Drosophila. Cell Rep. 2019;27(8):2480-2492.
https://doi.org/10.1016/j.celrep.2019.04.103
24.VL Hale, JM Watermeyer, F Hackett, G Vizcay-Barrena, C van Ooij, JA Thomas, MC Spink, M Harkiolaki, E Duke, RA Fleck, MJ Blackman, HR Saibil. Parasitophorous vacuole poration precedes its rupture and rapid host erythrocyte cytoskeleton collapse in Plasmodium falciparum egress. Proc. Natl. Acad. Sci. 2017; 114(13):3439-3444.
https://doi.org/10.1073/pnas.1619441114
25.J García-Nafría, M Harkiolaki**, R Persson, MJ Fogg, KS Wilson. The structure of Bacillus subtilis SPβ prophage dUTPase and its complexes with two nucleotides.Acta Crystallogr D Biol Crystallogr. 2011;67(Pt 3):167-75.
https://doi.org/10.1107/S0907444911003234
26.IK Macdonald, M Harkiolaki**, L Hunt, T Connelley, AV Carroll, ND MacHugh, SP Graham, EY Jones, WI Morrison, DR Flower, SA Ellis. MHC class I bound to an immunodominant Theileria parva epitope demonstrates unconventional presentation to T cell receptors. PLoS Pathog. 2010;6(10):e1001149.
https://doi.orf/10.1371/journal.ppat.1001149
27.M Harkiolaki, T Tsirka, M Lewitzky, PC Simister, D Joshi, LE Bird, EY Jones, N O'Reilly, SM Feller. Distinct binding modes of two epitopes in Gab2 that interact with the SH3C domain of Grb2. Structure. 2009;17(6):809-22.
https://doi.orh/10.1016/j.str.2009.03.017
28.M Harkiolaki, SL Holmes, P Svendsen, JW Gregersen, LT Jensen, R McMahon, MA Friese, G van Boxel, R Etzensperger, JS Tzartos, K Kranc, S Sainsbury, K Harlos, ED Mellins, J Palace, MM Esiri, PA van der Merwe, EY Jones, L Fugger. T cell-mediated autoimmune disease due to low-affinity crossreactivity to common microbial peptides. Immunity. 2009;30(3):348-57.
https://doi.org/10.1016/j.immuni.2009.01.009
29.AE Vidal, M Harkiolaki**, C Gallego, VM Castillo-Acosta, LM Ruiz-Pérez, K Wilson, D González-Pacanowska. Crystal structure and DNA repair activities of the AP endonuclease from Leishmania major.J. Mol. Biol. 2007;373(4):827-38.
https://doi.org/10.1016/j.jmb.2007.08.001
30.M Harkiolaki, RJ Gilbert, EY Jones, SM Feller. The C-terminal SH3 domain of CRKL as a dynamic dimerization module transiently exposing a nuclear export signal. Structure. 2006 Dec;14(12):1741-53.
https://doi.org/10.1016/j.str.2006.09.013
31.CS Hourigan, M Harkiolaki, NA Peterson, JI Bell, EY Jones, CA O'Callaghan. The structure of the human allo-ligand HLA-B*3501 in complex with a cytochrome p450 peptide: steric hindrance influences TCR allo-recognition. Eur. J. Immunol. 2006;36(12):3288-93.
https://doi.org/10.1002/eji.200636234
32.OV Moroz, M Harkiolaki, MY Galperin, AA Vagin, D González-Pacanowska, KS Wilson. The crystal structure of a complex of Campylobacter jejuni dUTPase with substrate analogue sheds light on the mechanism and suggests the "basic module" for dimeric d(C/U)TPases. J. Mol. Biol. 2004;342(5):1583-97.
https://doi.org/10.1016/j.jmb.2004.07.050
33.M Lewitzky, M Harkiolaki**, MC Domart, EY Jones, SM Feller. Mona/Gads SH3C binding to hematopoietic progenitor kinase 1 (HPK1) combines an atypical SH3 binding motif, R/KXXK, with a classical PXXP motif embedded in a polyproline type II (PPII) helix. J Biol Chem. 2004;279(27):28724-32.
https://doi.org/ 10.1074/jbc.M402745200
34.M Harkiolaki, EJ Dodson, V Bernier-Villamor, JP Turkenburg, D González-Pacanowska, KS Wilson. The crystal structure of Trypanosoma cruzi dUTPase reveals a novel dUTP/dUDP binding fold. Structure. 2004;12(1):41-53.
https://doi.org/10.1016/j.str.2003.11.016
35.M Harkiolaki, M Lewitzky, RJ Gilbert, EY Jones, RP Bourette, G Mouchiroud, H Sondermann, I Moarefi, SM Feller. Structural basis for SH3 domain-mediated high-affinity binding between Mona/Gads and SLP-76.EMBO J. 2003;22(11):2571-82. https://doi.org/10.1093/emboj/cdg258
https://doi.org/10.1093/emboj/cdg258
36.A Perrakis, M Harkiolaki, KS Wilson, VS Lamzin. ARP/wARP and molecular replacement. Acta Crystallogr. D Biol. Crystallogr. 2001;57(Pt 10):1445-50.
https://doi.org/10.1107/s0907444901014007
37.M Harkiolaki, AM Brzozowski, D Gonzalez-Pacanowska, F Hidalgo-Zarco, KS Wilson. New crystal forms of Trypanosoma cruzi dUTPase. Acta Crystallogr. D Biol. Crystallogr. 2001;57(Pt 6):915-7.
https://doi.org/10.1107/s0907444901004905
38.R Persson, M Harkiolaki, J McGeehan, KS Wilson. Crystallization and preliminary crystallographic analysis of deoxyuridine 5'-triphosphate nucleotidohydrolase from Bacillus subtilis. Acta Crystallogr. D Biol. Crystallogr. 2001;57(Pt 6):876-8.
https://doi.org/10.1107/s0907444901007727
* Corresponding author
** Joint first author
Peer-reviewed literature review publications
1.A Walter, E Pereiro, M Harkiolaki. Soft X-ray tomography. Chapter 34 in “Imaging Modalities for Biological and Preclinical Research: A Compendium, Volume 1” Edits Andreas Walter, Julia G Mannheim and Carmel J Caruana. IOP Publishing Ltd. 2021. https://doi.org/10.1088/978-0-7503-3059-6ch23
2.M Harkiolaki, MC Darrow, MC Spink, E Kosior, K Dent, E Duke. Cryo-soft X-ray tomography: using soft X-rays to explore the ultrastructure of whole cells.Emerg Top Life Sci.2018. Apr 20;2(1):81-92. https://doi.org/10.1042/ETLS20170086
3.M Spink, M Darrow, H Fisher, A Burt, K Marshall, I Luengo, M Harkiolaki, L Duke. Correlation of cryo soft x-ray tomography with cryo fluorescence microscopy to characterise cellular organelles at beamline B24, Diamond Light Source.Microscopy and Microanalysis. 2018. Aug 24(S2), 374-375. https://doi.org/10.1017/S1431927618014162
4M Darrow, M Harkiolaki, M Spink, I Luengo, M Basham, E Duke. Cryo soft x-ray tomography and other techniques at Diamond Light Source.Microscopy and Microanalysis. 2017. Aug. 23(S1), 972-973. https://doi.org/10.1017/S1431927617005529
