Maria Harkiolaki

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Maria Harkiolaki is the Principal Beamline Scientist for beamline B24. Maria joined Diamond in 2013 after working at the University of Oxford.

Email: maria.harkiolaki@diamond.ac.uk
Tel: +44 (0) 1235 778757

 

Maria is the Principal Beamline Scientist (equivalency to an associate professor) of the correlative cryo-imaging beamline B24 at the UK synchrotron Diamond Light Source. She is responsible for the design, build and application (including user support) and delivery of the facility which now encompasses an X-ray tomography setup with correlated super resolution fluorescence microscopy and a fully commissioned pipeline that involves all steps of the process from sample preparation to data analysis and dissemination. Her duties extend to teaching and supervision and she delivers both workshops and lectures on microscopy theory and applications (in person and online) while providing day-to-day supervision to a team of scientists, engineers, students, and technical staff.

Research-wise, she has an extensive network of collaborators (national and international from academia and industry) and a personal research portfolio that focuses on: (a) cutting-edge microscopy technology development, (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.

Before her appointment at Diamond, Maria was a Principal Investigator at the Structural Biology Division of the Nuffield Department of Medicine at the University of Oxford, UK from 2008 until 2012 (funded through a long-term fellowship from the European Molecular Biology Organisation and subsequently through a Royal Society Dorothy Hodgkin fellowship). Her research at the time focused on understanding the structure of molecular interactions that define antigen recognition and autoimmunity.

https://wearetechwomen.com/inspirational-woman-dr-maria-harkiolaki-principal-beamline-scientist-diamond-light-source/

  1. 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

  1. 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

  1. 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

  1. M Koronfel, I Kounatidis, DM Mwangangi, N Vyas, C Okolo,A  Jadhav, 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

  1. KL Nahas, J Ferreira Fernandes, CM Crump, SC Graham, M Harkiolaki*. Contour, a semi-automated segmentation and quantitation tool for cryo-soft-X-ray tomography. bioRxiv 2021.12.03.470962.

https://doi.org/10.1101/2021.12.03.470962

  1. KL Nahas, V Connor, M Harkiolaki*, CM Crump, SC Graham. Near-native state imaging by cryo-soft-X-ray tomography reveals remodelling of cytoplasmic vesicles and mitochondria during HSV-1 infection. bioRxiv 2021.10.11.463900. 

https://doi.org/10.1101/2021.10.11.463900

  1. 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

  1. 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

  1. 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

  1. 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

  1. 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

  1. 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

  1. 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

  1. 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

  1. 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

  1. 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

  1. 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

  1. 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

  1. 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

  1. 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

  1. 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

  1. 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.

https://aip.scitation.org/doi/abs/10.1063/1.5084675

  1. 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

  1. 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

  1. 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

  1. 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

  1. 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

  1. 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

  1. 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

  1. 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

  1. 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

  1. 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

  1. 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

  1. 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

  1. 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

  1. 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

  1. 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

  1. 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

 

Dr Harkiolaki has been at Diamond since 2012. She has been involved with the design, procurement and installation of B24 components as well as the development of other high resolution microscopy methods that will be used in a correlative fashion to the data generated by the B24 full field X-ray microscope. Previously, she was a Principal Investigator at the Structural Biology Laboratory at the Nuffield Department of Clinical Medicine of the University of Oxford. While there she worked on a range of biomedical research projects with emphasis initially on human adaptive immunity, later expanding to model studies of innate immunity. In specific, she studied MHC class II molecules relating to multiple sclerosis, MHC class I molecules relating to allo reactivity & HIV response as well as MHC class I complexes expressed upon antigenic challenge in livestock. Moreover, she has developed a library of innate immunity molecules relating to two species of honey bee: western and asiatic, to be studied further and in conjunction with emerging data from other laboratories. Dr Harkiolaki studied for her PhD at the University of York, under the supervision of Professors K. Wilson and E. Dodson.

 

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

 

4 M 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

 

1. New x-ray imaging technique investigates cells hosting Chlamydiae bacteria. Physorg 2021. https://phys.org/news/2021-09-x-ray-imaging-technique-cells-hosting.html

 

2. 3D high-res cryo-imaging reveals organisational behaviour of chlamydiae bacteria. Diamond Light Source News 2021.https://www.diamond.ac.uk/Home/News/LatestNews/2021/22-09-21.html

 

3. Super-resolution 3D cryo imaging techniques for vaccine candidate assessment. Diamond Science Highlights 2021. https://www.diamond.ac.uk/Science/Research/Highlights/2021/Super-resolution-3D-cryo-imaging-techniques-for-vaccine-candidate-assessment.html

 

4. Kounatidis I, Harkiolaki M. Correlative imaging - a novel approach to investigate the cellular world. ScientistLive 2021. https://www.scientistlive.com/content/correlative-imaging-novel-approach-investigate-cellular-world

 

5. Okolo CA, Harkiolaki M. The intracellular world in 3D and in colour: developments at the biological cryo-imaging beamline B24 at the UK’s national synchrotron, Diamond Light Source. Labmate Online 2020. https://www.labmate-online.com/article/microscopy-and-microtechniques/4/diamond-light-source-ltd/the-intracellular-world-in-3d-and-in-colour-developments-at-the-biological-cryo-imaging-beamline-b24-at-the-ukrsquos-national-synchrotron-diamond-light-source/2825

 

6. Harkiolaki M. The dynamic duo. Diamond Light Source. ScientistLive 2020. https://www.scientistlive.com/content/dynamic-duo

 

 

1. DPhil in Chemistry (April 2002), University of York, UK.

 

2. BSc in Biochemistry (July 1995) Wichita State University, Kansas, USA.

 

 

Structural immunology, innate and adaptive immunity, pathogen recognition & adaptation.

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