Dr Pierre Rizkallah
Rcuk Fellow
- RizkallahP@cardiff.ac.uk
- +44 652248
- Sir Geraint Evans Cardiovascular Research Building, Room 3/05, University Hospital of Wales, Heath Park, Cardiff, CF14 4XN
- Media commentator
- Available for postgraduate supervision
Overview
I am a senior lecturer in Structural Biology. I specialise in studying shapes of biological molecules at the atomic level, to infer ways and mechanisms of interactions between different molecules of life. I have conducted research in many different fields of Life Sciences, affording an understanding of biological communications in a variety of systems. This opened up the ability to design therapies for different complaints, an area at the heart of my research. It is also an opportunity to design diagnostics and to use biotechnology to enable processes that do not occur naturally.
I am a Chemistry graduate, at BSc and PhD level. I use Physics applications to study biological macromolecules. I have extensive experience with X-ray crystallography and 3D structure determination using synchrotron radiation. I have used the allied techniques of Small Angle X-ray Scattering (SAXS) and Circular Dichroism (CD) to shed light on biological mechanisms.
I have served on committees and participated in programs at national and international levels. I have conducted many outreach and media exercises during the course of my career, communicating the immediacy relevance and importance of Science in everyday life.
I had a brief period of experience in the cosmetics industry, leading a production line team.
Publication
2023
- Owens, H. A. et al. 2023. Alzheimer’s disease associated P460Lvariant of EphA1 dysregulates receptor activity and blood brain barrier function. Alzheimer's & Dementia: The Journal of the Alzheimer's Association
- Mundy, R. M. et al. 2023. Broad sialic acid usage amongst species D human adenovirus. npj Viruses 1, article number: 1. (10.1038/s44298-023-00001-5)
- Chen, Y. et al. 2023. Structural definition of HLA class II-presented SARS-CoV-2 epitopes reveals a mechanism to escape pre-existing CD4+ T cell immunity. Cell Reports 42(8), article number: 112827. (10.1016/j.celrep.2023.112827)
- Dolton, G. et al. 2023. Targeting of multiple tumor-associated antigens by individual T cell receptors during successful cancer immunotherapy. Cell 186(16), pp. 3333-3349., article number: E27. (10.1016/j.cell.2023.06.020)
2022
- Best, H. L., Williamson, L. J., Lipka-Lloyd, M., Waller-Evans, H., Lloyd-Evans, E., Rizkallah, P. J. and Berry, C. 2022. The crystal structure of Bacillus thuringiensis Tpp80Aa1 and its interaction with galactose-containing glycolipids. Toxins 14(12), article number: 863. (10.3390/toxins14120863)
- Dolton, G. et al. 2022. Emergence of immune escape at dominant SARS-CoV-2 killer T cell epitope. Cell 185(16), pp. 2936-2951. (10.1016/j.cell.2022.07.002)
- Bates, E. A. et al. 2022. Development of a low seroprevalence, αvβ6 integrin selective virotherapy based on human adenovirus type 10. Molecular Therapy - Oncolytics 25, pp. 43-56. (10.1016/j.omto.2022.03.007)
- Noby, N. et al. 2022. Structure-guided engineering of a family IV cold-adapted esterase expands its substrate range. International Journal of Molecular Sciences 23(9), article number: 4703. (10.3390/ijms23094703)
2021
- Noby, N. et al. 2021. Structure and in silico simulations of a cold-active esterase reveals its prime cold-adaptation mechanism. Open Biology 11(12), article number: 210182. (10.1098/rsob.210182)
- Baker, A. T. et al. 2021. ChAdOx1 interacts with CAR and PF4 with implications for thrombosis with thrombocytopenia syndrome. Science Advances 7(49), article number: eabl8213. (10.1126/sciadv.abl8213)
- Griffiths, J. S. et al. 2021. A human Dectin-2 deficiency associated with invasive aspergillosis. Journal of Infectious Diseases 224(7), pp. 1219-1224. (10.1093/infdis/jiab145)
- Man, S. et al. 2021. Synthetic peptides with inadvertent chemical modifications can activate potentially autoreactive T cells. Journal of Immunology 207(4), pp. 1009-1017. (10.4049/jimmunol.2000756)
- Worthy, H. L. et al. 2021. The crystal sructure of Bacillus cereus HblL1. Toxins 13(4), article number: 253. (10.3390/toxins13040253)
- Baker, A. T. et al. 2021. The fiber knob protein of human adenovirus type 49 mediates highly efficient and promiscuous infection of cancer cell lines using a novel cell entry mechanism. Journal of Virology 95(4), article number: e01849-20. (10.1128/JVI.01849-20)
- Pope, J. R. et al. 2021. Association of fluorescent protein pairs and it's significant impact on fluorescence and energy transfer. Advanced Science 8(1), article number: 2003167. (10.1002/advs.202003167)
2020
- Mowbray, N. G. et al. 2020. Safe management of surgical smoke in the age of COVID-19. British Journal of Surgery 107(11), pp. 1406-1413. (10.1002/bjs.11679)
- Bovay, A. et al. 2020. Identification of a superagonist variant of the immunodominant Yellow fever virus epitope NS4b214-222 by combinatorial peptide library screening. Molecular Immunology 125, pp. 43-50. (10.1016/j.molimm.2020.06.025)
- Greenshields-Watson, A. et al. 2020. CD4 + T cells recognize conserved influenza A epitopes through shared patterns of V-Gene usage and complementary biochemical features. Cell Reports 32(2), article number: 107885. (10.1016/j.celrep.2020.107885)
- Holland, C. J. et al. 2020. Specificity of bispecific T cell receptors and antibodies targeting peptide-HLA. Journal of Clinical Investigation 130(5), pp. 2673–2688. (10.1172/JCI130562)
- Cresser-Brown, J., Rizkallah, P., Jin, Y., Roth, C., Miller, D. J. and Allemann, R. K. 2020. An unexpected co-crystal structure of the calpain PEF(S) domain with Hfq reveals a potential chaperone function of Hfq. Acta Crystallographica Section F: Structural Biology Communications 76(2), pp. 81-85. (10.1107/S2053230X20001181)
2019
- MacLachlan, B. J. et al. 2019. Human leukocyte antigen (HLA) class II peptide flanking residues tune the immunogenicity of a human tumor-derived epitope. Journal of Biological Chemistry 294(52), pp. 20246-20258. (10.1074/jbc.RA119.009437)
- Worthy, H. L. et al. 2019. Positive functional synergy of structurally integrated artificial protein dimers assembled by Click chemistry. Communications Chemistry 2, article number: 83. (10.1038/s42004-019-0185-5)
- Madura, F. et al. 2019. TCR-induced alteration of primary MHC peptide anchor residue. European Journal of Immunology 49(7), pp. 1052-1066. (10.1002/eji.201948085)
- Kalvaitis, M. E., Johnson, L. A., Mart, R. J., Rizkallah, P. and Allemann, R. K. 2019. A noncanonical chromophore reveals structural rearrangements of the light-oxygen-voltage domain upon photoactivation. Biochemistry 58(22), pp. 2608-2616. (10.1021/acs.biochem.9b00255)
- Scott, A. F., Cresser-Brown, J., Williams, T. L., Rizkallah, P. J., Jin, Y., Luk, L. Y. and Allemann, R. K. 2019. Crystal structure and biophysical analysis of furfural detoxifying aldehyde reductase from clostridium beijerinkii. Applied and Environmental Microbiology (10.1128/AEM.00978-19)
- Galloway, S. A. E. et al. 2019. Peptide super-agonist enhances T-cell responses to melanoma. Frontiers in Immunology 10, article number: 319. (10.3389/fimmu.2019.00319)
- Baker, A. T. et al. 2019. Diversity within the adenovirus fiber knob hypervariable loops influences primary receptor interactions. Nature Communications 10, article number: 741. (10.1038/s41467-019-08599-y)
2018
- Uusi-Kerttula, H. et al. 2018. Ad5NULL-A20 - a tropism-modified, αvβ6 integrin-selective oncolytic adenovirus for epithelial ovarian cancer therapies. Clinical Cancer Research 24(17), pp. 4215-4224. (10.1158/1078-0432.CCR-18-1089)
- Tungatt, K. et al. 2018. Induction of influenza-specific local CD8 T-cells in the respiratory tract after aerosol delivery of vaccine antigen or virus in the Babraham inbred pig. PLoS Pathogens 14(5), article number: e1007017. (10.1371/journal.ppat.1007017)
- Holland, C. J. et al. 2018. In silico and structural analyses demonstrate that intrinsic protein motions guide T cell receptor complementarity determining region loop flexibility. Frontiers in Immunology 9, article number: 674. (10.3389/fimmu.2018.00674)
- Miles, J. J. et al. 2018. Peptide mimic for influenza vaccination using nonnatural combinatorial chemistry. Journal of Clinical Investigation 128(4), pp. 1569-1580. (10.1172/JCI91512)
- Bovay, A. et al. 2018. T cell receptor alpha variable 12-2 bias in the immunodominant response to Yellow fever virus. European Journal of Immunology 48(2), pp. 258-272. (10.1002/eji.201747082)
2017
- Cole, D. K. et al. 2017. Dual molecular mechanisms govern escape at immunodominant HLA A2-restricted HIV epitope. Frontiers in Immunology 8, article number: 1503. (10.3389/fimmu.2017.01503)
- MacLachlan, B. J. et al. 2017. Using X-ray crystallography, biophysics, and functional assays to determine the mechanisms governing T-cell receptor recognition of cancer antigens. Journal of Visualized Experiments(120), article number: e54991. (10.3791/54991)
- Cole, D. K. et al. 2017. Structural mechanism underpinning cross-reactivity of a CD8+ T-cell clone that recognises a peptide derived from human telomerase reverse transcriptase. Journal of Biological Chemistry 292(3), pp. 802-813. (10.1074/jbc.M116.741603)
2016
- Nomikos, M. et al. 2016. Mutations in PLCd1 associated with hereditary leukonychia display divergent PIP2 hydrolytic function. FEBS Journal 283(24), pp. 4502-4514. (10.1111/febs.13939)
- Hartley, A. M., Worthy, H. L., Reddington, S. C., Rizkallah, P. J. and Jones, D. D. 2016. Molecular basis for functional switching of GFP by two disparate non-native post-translational modifications of a phenyl azide reaction handle. Chemical Science 7(10), pp. 6484-6491. (10.1039/C6SC00944A)
- Cole, D. K. et al. 2016. Hotspot autoimmune T cell receptor binding underlies pathogen and insulin peptide cross-reactivity. Journal of Clinical Investigation 126(6), pp. 2191-2204. (10.1172/JCI85679)
- Bianchi, V. et al. 2016. A molecular switch abrogates glycoprotein 100 (gp100) T-cell Receptor (TCR) targeting of a human melanoma antigen. Journal of Biological Chemistry 291(17), pp. 8951-8959. (10.1074/jbc.M115.707414)
- Raman, M. C. C. et al. 2016. Direct molecular mimicry enables off-target cardiovascular toxicity by an enhanced affinity TCR designed for cancer immunotherapy. Scientific Reports 6, article number: 18851. (10.1038/srep18851)
2015
- Adams, S., Robinson, E., Miller, D. J., Rizkallah, P., Hallett, M. B. and Allemann, R. K. 2015. Conformationally restricted calpain inhibitors. Chemical Science 6(12), pp. 6865-6871. (10.1039/c5sc01158b)
- Motozono, C. et al. 2015. Distortion of the major histocompatibility complex class I binding groove to accommodate an insulin-derived 10-Mer peptide. Journal of Biological Chemistry 290(31), pp. 18924-18933. (10.1074/jbc.M114.622522)
- Reid, R., Redman, J. E., Rizkallah, P., Fegan, C. D., Pepper, C. J. and Man, S. T. 2015. CD8+ T-cell recognition of a synthetic epitope formed by t-butyl modification. Immunology 144(3), pp. 495-505. (10.1111/imm.12398)
- Madura, F. et al. 2015. Structural basis for ineffective T-cell responses to MHC anchor residue-improved 'heteroclitic' peptides. European Journal of Immunology 45(2), pp. 584-591. (10.1002/eji.201445114)
- Kløverpris, H. N. et al. 2015. A molecular switch in immunodominant HIV-1-specific CD8 T-cell epitopes shapes differential HLA-restricted escape. Retrovirology 12(1), article number: 20. (10.1186/s12977-015-0149-5)
- Reddington, S. C., Driezis, S., Hartley, A. M., Watson, P. D., Rizkallah, P. J. and Jones, D. D. 2015. Genetically encoded phenyl azide photochemistry drives positive and negative functional modulation of a red fluorescent protein. RSC Advances 5(95), pp. 77734-77738. (10.1039/C5RA13552D)
2014
- Adams, S. E., Rizkallah, P., Miller, D. J., Robinson, E. J., Hallett, M. B. and Allemann, R. K. 2014. The structural basis of differential inhibition of human calpain by indole and phenyl α--mercaptoacrylic acids. Journal of Structural Biology 187(3), pp. 236-241. (10.1016/j.jsb.2014.07.004)
- Nomikos, M. et al. 2014. Altered RyR2 regulation by the calmodulin F90L mutation associated with idiopathic ventricular fibrillation and early sudden cardiac death. Febs Letters 588(17), pp. 2898-2902. (10.1016/j.febslet.2014.07.007)
- Arpino, J. J., Reddington, S. C., Halliwell, L., Rizkallah, P. and Jones, D. D. 2014. Random single amino acid deletion sampling unveils structural tolerance and the benefits of helical registry shift on GFP folding and structure. Structure 22(6), pp. 889-898. (10.1016/j.str.2014.03.014)
- Motozono, C. et al. 2014. Molecular basis of a dominant T cell response to an HIV reverse transcriptase 8-mer epitope presented by the protective allele HLA-B*51:01. The Journal of Immunology 192(7), pp. 3428-3434. (10.4049/jimmunol.1302667)
- Arpino, J. A. J., Rizkallah, P. and Jones, D. D. 2014. Structural and dynamic changes associated with beneficial engineered single-amino-acid deletion mutations in enhanced green fluorescent protein. Acta Crystallographica Section D Biological Crystallography 70(8), pp. 2152-2162. (10.1107/S139900471401267X)
2013
- Cole, D. et al. 2013. Increased peptide contacts govern high affinity binding of a modified TCR whilst maintaining a native pMHC docking mode. Frontiers in Immunology 4, article number: 168. (10.3389/fimmu.2013.00168)
- Reddington, S. C., Rizkallah, P., Watson, P. D., Pearson, R., Tippmann, E. M. and Jones, D. D. 2013. Different photochemical events of a genetically encoded phenyl azide define and modulate GFP fluorescence. Angewandte Chemie - International Edition 52(23), pp. 5974-5977. (10.1002/anie.201301490)
- Madura, F. et al. 2013. T-cell receptor specificity maintained by altered thermodynamics. Journal of Biological Chemistry 288(26), pp. 18766-18775. (10.1074/jbc.M113.464560)
- Eukeruche-Makinde, J. et al. 2013. Peptide length determines the outcome of TCR/peptide-MHCI engagement. Blood -New York- 121(7), pp. 1112-1123. (10.1182/blood-2012-06-437202)
- Ekeruche, J. et al. 2013. Peptide length determines the outcome of TCR/peptide-MHCI engagement. Blood 121(7), pp. 1112-1123. (10.1182/blood-2012-06-437202)
- Cole, D. et al. 2013. T-cell Receptor (TCR)-Peptide Specificity Overrides Affinity-enhancing TCR-Major Histocompatibility Complex Interactions. Journal of Biological Chemistry 289(2), pp. 628-638. (10.1074/jbc.M113.522110)
- Reddington, S. C., Watson, P. D., Rizkallah, P., Tippmann, E. M. and Jones, D. D. 2013. Genetically encoding phenyl azide chemistry: new uses and ideas for classical biochemistry. Biochemical Society Transactions 41(5), pp. 1177-1182. (10.1042/BST20130094)
2012
- Ekeruche, J. et al. 2012. T-cell receptor-optimized peptide skewing of the T-cell repertoire can enhance antigen targeting. Journal of Biological Chemistry 287(44), pp. 37269-37281. (10.1074/jbc.M112.386409)
- Ekeruche-Makinde, J. et al. 2012. T-cell receptor-optimized peptide skewing of the T-cell repertoire can enhance antigen targeting. Journal of Biological Chemistry 287(44), pp. 37269-37281. (10.1074/jbc.M112.386409)
- Holland, C. J. et al. 2012. Minimal conformational plasticity enables TCR cross-reactivity to different MHC class II heterodimers. Scientific Reports 2, article number: 629. (10.1038/srep00629)
- Bulek, A. M. et al. 2012. TCR/pMHC optimized protein crystallization screen. Journal of Immunological Methods 382(1-2), pp. 203-210. (10.1016/j.jim.2012.06.007)
- Yang, S. et al. 2012. A partially interpenetrated metal-organic framework for selective hysteretic sorption of carbon dioxide. Nature Materials 11(8), pp. 710-716. (10.1038/nmat3343)
- Bulek, A. et al. 2012. Structural basis for the killing of human beta cells by CD8+ T cells in type 1 diabetes. Nature Immunology 13(3), pp. 283-289. (10.1038/ni.2206)
- Bulek, A. M. et al. 2012. Structural basis for the killing of human beta cells by CD8+ T cells in type 1 diabetes. Nature Immunology 13(3), pp. 283-289. (10.1038/ni.2206)
- Arpino, J., Rizkallah, P. and Jones, D. D. 2012. Crystal structure of enhanced green fluorescent protein to 1.35 Å resolution reveals alternative conformations for Glu222. PLoS ONE 7(10), article number: e47132. (10.1371/journal.pone.0047132)
- Tadesse, H., Blake, A. J., Champness, N. R., Warren, J. E., Rizkallah, P. and Licence, P. 2012. Supramolecular architectures of symmetrical dicationic ionic liquid based systems. Crystengcomm 14(15), pp. 4886-4893. (10.1039/c2ce25106j)
2011
- Lane, S. W., Dennis, C. A., Lane, C. L., Trinh, C. H., Rizkallah, P., Stockley, P. G. and Phillips, S. E. V. 2011. Construction and crystal structure of recombinant STNV capsids. Journal of Molecular Biology 413(1), pp. 41-50. (10.1016/j.jmb.2011.07.062)
2010
- Miles, J. J. et al. 2010. Genetic and structural basis for selection of a ubiquitous T cell receptor deployed in Epstein-Barr virus infection. PLoS Pathogens 6(11), article number: e1001198. (10.1371/journal.ppat.1001198)
- Ronson, T. K., Carruthers, C., Fisher, J., Brotin, T., Harding, L. P., Rizkallah, P. and Hardie, M. J. 2010. Tripodal 4-pyridyl-derived host ligands and their metallo-supramolecular chemistry: stella octangula and bowl-shaped assemblies. Inorganic Chemistry -American Chemical Society- 49(2), pp. 675-685. (10.1021/ic901972h)
2009
- Ronson, T. K., Fisher, J., Harding, L. P., Rizkallah, P., Warren, J. E. and Hardie, M. J. 2009. Stellated polyhedral assembly of a topologically complicated Pd4L4 'Solomon cube'. Nature Chemistry 1(3), pp. 212-216. (10.1038/nchem.213)
- Cole, D. et al. 2009. Germ line-governed recognition of a cancer epitope by an immunodominant human T-cell receptor. Journal of Biological Chemistry 284(40), article number: 27281-27289. (10.1074/jbc.M109.022509)
2008
- Govada, L. et al. 2008. Crystal structure of the C1 domain of cardiac myosin binding protein-C: Implications for hypertrophic cardiomyopathy. Journal of Molecular Biology 378(2), pp. 387-397. (10.1016/j.jmb.2008.02.044)
- Westcott, A., Fisher, J., Harding, L. P., Rizkallah, P. and Hardie, M. J. 2008. Self-assembly of a 3-D triply interlocked chiral [2] catenane. Journal of the American Chemical Society 130(10), pp. 2950-2951. (10.1021/ja8002149)
2007
- Cole, D. et al. 2007. Computational design and crystal structure of an enhanced affinity mutant human CD8 αα coreceptor. Proteins: Structure, Function and Bioinformatics 67(1), pp. 65-74. (10.1002/prot.21176)
2006
- Cole, D. et al. 2006. Crystal structure of HLA-A*2402 complexed with a telomerase peptide. European Journal of Immunology 36(1), pp. 170-179. (10.1002/eji.200535424)
2005
- Cole, D. et al. 2005. Crystallization and preliminary X-ray structural studies of a high-affinity CD8αα co-receptor to pMHC. Acta Crystallographica Section F: Structural Biology and Crystallization Communications 61(3), pp. 285-287. (10.1107/S1744309105002988)
Articles
- Owens, H. A. et al. 2023. Alzheimer’s disease associated P460Lvariant of EphA1 dysregulates receptor activity and blood brain barrier function. Alzheimer's & Dementia: The Journal of the Alzheimer's Association
- Mundy, R. M. et al. 2023. Broad sialic acid usage amongst species D human adenovirus. npj Viruses 1, article number: 1. (10.1038/s44298-023-00001-5)
- Chen, Y. et al. 2023. Structural definition of HLA class II-presented SARS-CoV-2 epitopes reveals a mechanism to escape pre-existing CD4+ T cell immunity. Cell Reports 42(8), article number: 112827. (10.1016/j.celrep.2023.112827)
- Dolton, G. et al. 2023. Targeting of multiple tumor-associated antigens by individual T cell receptors during successful cancer immunotherapy. Cell 186(16), pp. 3333-3349., article number: E27. (10.1016/j.cell.2023.06.020)
- Best, H. L., Williamson, L. J., Lipka-Lloyd, M., Waller-Evans, H., Lloyd-Evans, E., Rizkallah, P. J. and Berry, C. 2022. The crystal structure of Bacillus thuringiensis Tpp80Aa1 and its interaction with galactose-containing glycolipids. Toxins 14(12), article number: 863. (10.3390/toxins14120863)
- Dolton, G. et al. 2022. Emergence of immune escape at dominant SARS-CoV-2 killer T cell epitope. Cell 185(16), pp. 2936-2951. (10.1016/j.cell.2022.07.002)
- Bates, E. A. et al. 2022. Development of a low seroprevalence, αvβ6 integrin selective virotherapy based on human adenovirus type 10. Molecular Therapy - Oncolytics 25, pp. 43-56. (10.1016/j.omto.2022.03.007)
- Noby, N. et al. 2022. Structure-guided engineering of a family IV cold-adapted esterase expands its substrate range. International Journal of Molecular Sciences 23(9), article number: 4703. (10.3390/ijms23094703)
- Noby, N. et al. 2021. Structure and in silico simulations of a cold-active esterase reveals its prime cold-adaptation mechanism. Open Biology 11(12), article number: 210182. (10.1098/rsob.210182)
- Baker, A. T. et al. 2021. ChAdOx1 interacts with CAR and PF4 with implications for thrombosis with thrombocytopenia syndrome. Science Advances 7(49), article number: eabl8213. (10.1126/sciadv.abl8213)
- Griffiths, J. S. et al. 2021. A human Dectin-2 deficiency associated with invasive aspergillosis. Journal of Infectious Diseases 224(7), pp. 1219-1224. (10.1093/infdis/jiab145)
- Man, S. et al. 2021. Synthetic peptides with inadvertent chemical modifications can activate potentially autoreactive T cells. Journal of Immunology 207(4), pp. 1009-1017. (10.4049/jimmunol.2000756)
- Worthy, H. L. et al. 2021. The crystal sructure of Bacillus cereus HblL1. Toxins 13(4), article number: 253. (10.3390/toxins13040253)
- Baker, A. T. et al. 2021. The fiber knob protein of human adenovirus type 49 mediates highly efficient and promiscuous infection of cancer cell lines using a novel cell entry mechanism. Journal of Virology 95(4), article number: e01849-20. (10.1128/JVI.01849-20)
- Pope, J. R. et al. 2021. Association of fluorescent protein pairs and it's significant impact on fluorescence and energy transfer. Advanced Science 8(1), article number: 2003167. (10.1002/advs.202003167)
- Mowbray, N. G. et al. 2020. Safe management of surgical smoke in the age of COVID-19. British Journal of Surgery 107(11), pp. 1406-1413. (10.1002/bjs.11679)
- Bovay, A. et al. 2020. Identification of a superagonist variant of the immunodominant Yellow fever virus epitope NS4b214-222 by combinatorial peptide library screening. Molecular Immunology 125, pp. 43-50. (10.1016/j.molimm.2020.06.025)
- Greenshields-Watson, A. et al. 2020. CD4 + T cells recognize conserved influenza A epitopes through shared patterns of V-Gene usage and complementary biochemical features. Cell Reports 32(2), article number: 107885. (10.1016/j.celrep.2020.107885)
- Holland, C. J. et al. 2020. Specificity of bispecific T cell receptors and antibodies targeting peptide-HLA. Journal of Clinical Investigation 130(5), pp. 2673–2688. (10.1172/JCI130562)
- Cresser-Brown, J., Rizkallah, P., Jin, Y., Roth, C., Miller, D. J. and Allemann, R. K. 2020. An unexpected co-crystal structure of the calpain PEF(S) domain with Hfq reveals a potential chaperone function of Hfq. Acta Crystallographica Section F: Structural Biology Communications 76(2), pp. 81-85. (10.1107/S2053230X20001181)
- MacLachlan, B. J. et al. 2019. Human leukocyte antigen (HLA) class II peptide flanking residues tune the immunogenicity of a human tumor-derived epitope. Journal of Biological Chemistry 294(52), pp. 20246-20258. (10.1074/jbc.RA119.009437)
- Worthy, H. L. et al. 2019. Positive functional synergy of structurally integrated artificial protein dimers assembled by Click chemistry. Communications Chemistry 2, article number: 83. (10.1038/s42004-019-0185-5)
- Madura, F. et al. 2019. TCR-induced alteration of primary MHC peptide anchor residue. European Journal of Immunology 49(7), pp. 1052-1066. (10.1002/eji.201948085)
- Kalvaitis, M. E., Johnson, L. A., Mart, R. J., Rizkallah, P. and Allemann, R. K. 2019. A noncanonical chromophore reveals structural rearrangements of the light-oxygen-voltage domain upon photoactivation. Biochemistry 58(22), pp. 2608-2616. (10.1021/acs.biochem.9b00255)
- Scott, A. F., Cresser-Brown, J., Williams, T. L., Rizkallah, P. J., Jin, Y., Luk, L. Y. and Allemann, R. K. 2019. Crystal structure and biophysical analysis of furfural detoxifying aldehyde reductase from clostridium beijerinkii. Applied and Environmental Microbiology (10.1128/AEM.00978-19)
- Galloway, S. A. E. et al. 2019. Peptide super-agonist enhances T-cell responses to melanoma. Frontiers in Immunology 10, article number: 319. (10.3389/fimmu.2019.00319)
- Baker, A. T. et al. 2019. Diversity within the adenovirus fiber knob hypervariable loops influences primary receptor interactions. Nature Communications 10, article number: 741. (10.1038/s41467-019-08599-y)
- Uusi-Kerttula, H. et al. 2018. Ad5NULL-A20 - a tropism-modified, αvβ6 integrin-selective oncolytic adenovirus for epithelial ovarian cancer therapies. Clinical Cancer Research 24(17), pp. 4215-4224. (10.1158/1078-0432.CCR-18-1089)
- Tungatt, K. et al. 2018. Induction of influenza-specific local CD8 T-cells in the respiratory tract after aerosol delivery of vaccine antigen or virus in the Babraham inbred pig. PLoS Pathogens 14(5), article number: e1007017. (10.1371/journal.ppat.1007017)
- Holland, C. J. et al. 2018. In silico and structural analyses demonstrate that intrinsic protein motions guide T cell receptor complementarity determining region loop flexibility. Frontiers in Immunology 9, article number: 674. (10.3389/fimmu.2018.00674)
- Miles, J. J. et al. 2018. Peptide mimic for influenza vaccination using nonnatural combinatorial chemistry. Journal of Clinical Investigation 128(4), pp. 1569-1580. (10.1172/JCI91512)
- Bovay, A. et al. 2018. T cell receptor alpha variable 12-2 bias in the immunodominant response to Yellow fever virus. European Journal of Immunology 48(2), pp. 258-272. (10.1002/eji.201747082)
- Cole, D. K. et al. 2017. Dual molecular mechanisms govern escape at immunodominant HLA A2-restricted HIV epitope. Frontiers in Immunology 8, article number: 1503. (10.3389/fimmu.2017.01503)
- MacLachlan, B. J. et al. 2017. Using X-ray crystallography, biophysics, and functional assays to determine the mechanisms governing T-cell receptor recognition of cancer antigens. Journal of Visualized Experiments(120), article number: e54991. (10.3791/54991)
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- Cole, D. K. et al. 2016. Hotspot autoimmune T cell receptor binding underlies pathogen and insulin peptide cross-reactivity. Journal of Clinical Investigation 126(6), pp. 2191-2204. (10.1172/JCI85679)
- Bianchi, V. et al. 2016. A molecular switch abrogates glycoprotein 100 (gp100) T-cell Receptor (TCR) targeting of a human melanoma antigen. Journal of Biological Chemistry 291(17), pp. 8951-8959. (10.1074/jbc.M115.707414)
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- Adams, S., Robinson, E., Miller, D. J., Rizkallah, P., Hallett, M. B. and Allemann, R. K. 2015. Conformationally restricted calpain inhibitors. Chemical Science 6(12), pp. 6865-6871. (10.1039/c5sc01158b)
- Motozono, C. et al. 2015. Distortion of the major histocompatibility complex class I binding groove to accommodate an insulin-derived 10-Mer peptide. Journal of Biological Chemistry 290(31), pp. 18924-18933. (10.1074/jbc.M114.622522)
- Reid, R., Redman, J. E., Rizkallah, P., Fegan, C. D., Pepper, C. J. and Man, S. T. 2015. CD8+ T-cell recognition of a synthetic epitope formed by t-butyl modification. Immunology 144(3), pp. 495-505. (10.1111/imm.12398)
- Madura, F. et al. 2015. Structural basis for ineffective T-cell responses to MHC anchor residue-improved 'heteroclitic' peptides. European Journal of Immunology 45(2), pp. 584-591. (10.1002/eji.201445114)
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- Reddington, S. C., Driezis, S., Hartley, A. M., Watson, P. D., Rizkallah, P. J. and Jones, D. D. 2015. Genetically encoded phenyl azide photochemistry drives positive and negative functional modulation of a red fluorescent protein. RSC Advances 5(95), pp. 77734-77738. (10.1039/C5RA13552D)
- Adams, S. E., Rizkallah, P., Miller, D. J., Robinson, E. J., Hallett, M. B. and Allemann, R. K. 2014. The structural basis of differential inhibition of human calpain by indole and phenyl α--mercaptoacrylic acids. Journal of Structural Biology 187(3), pp. 236-241. (10.1016/j.jsb.2014.07.004)
- Nomikos, M. et al. 2014. Altered RyR2 regulation by the calmodulin F90L mutation associated with idiopathic ventricular fibrillation and early sudden cardiac death. Febs Letters 588(17), pp. 2898-2902. (10.1016/j.febslet.2014.07.007)
- Arpino, J. J., Reddington, S. C., Halliwell, L., Rizkallah, P. and Jones, D. D. 2014. Random single amino acid deletion sampling unveils structural tolerance and the benefits of helical registry shift on GFP folding and structure. Structure 22(6), pp. 889-898. (10.1016/j.str.2014.03.014)
- Motozono, C. et al. 2014. Molecular basis of a dominant T cell response to an HIV reverse transcriptase 8-mer epitope presented by the protective allele HLA-B*51:01. The Journal of Immunology 192(7), pp. 3428-3434. (10.4049/jimmunol.1302667)
- Arpino, J. A. J., Rizkallah, P. and Jones, D. D. 2014. Structural and dynamic changes associated with beneficial engineered single-amino-acid deletion mutations in enhanced green fluorescent protein. Acta Crystallographica Section D Biological Crystallography 70(8), pp. 2152-2162. (10.1107/S139900471401267X)
- Cole, D. et al. 2013. Increased peptide contacts govern high affinity binding of a modified TCR whilst maintaining a native pMHC docking mode. Frontiers in Immunology 4, article number: 168. (10.3389/fimmu.2013.00168)
- Reddington, S. C., Rizkallah, P., Watson, P. D., Pearson, R., Tippmann, E. M. and Jones, D. D. 2013. Different photochemical events of a genetically encoded phenyl azide define and modulate GFP fluorescence. Angewandte Chemie - International Edition 52(23), pp. 5974-5977. (10.1002/anie.201301490)
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- Ekeruche, J. et al. 2013. Peptide length determines the outcome of TCR/peptide-MHCI engagement. Blood 121(7), pp. 1112-1123. (10.1182/blood-2012-06-437202)
- Cole, D. et al. 2013. T-cell Receptor (TCR)-Peptide Specificity Overrides Affinity-enhancing TCR-Major Histocompatibility Complex Interactions. Journal of Biological Chemistry 289(2), pp. 628-638. (10.1074/jbc.M113.522110)
- Reddington, S. C., Watson, P. D., Rizkallah, P., Tippmann, E. M. and Jones, D. D. 2013. Genetically encoding phenyl azide chemistry: new uses and ideas for classical biochemistry. Biochemical Society Transactions 41(5), pp. 1177-1182. (10.1042/BST20130094)
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- Bulek, A. M. et al. 2012. TCR/pMHC optimized protein crystallization screen. Journal of Immunological Methods 382(1-2), pp. 203-210. (10.1016/j.jim.2012.06.007)
- Yang, S. et al. 2012. A partially interpenetrated metal-organic framework for selective hysteretic sorption of carbon dioxide. Nature Materials 11(8), pp. 710-716. (10.1038/nmat3343)
- Bulek, A. et al. 2012. Structural basis for the killing of human beta cells by CD8+ T cells in type 1 diabetes. Nature Immunology 13(3), pp. 283-289. (10.1038/ni.2206)
- Bulek, A. M. et al. 2012. Structural basis for the killing of human beta cells by CD8+ T cells in type 1 diabetes. Nature Immunology 13(3), pp. 283-289. (10.1038/ni.2206)
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- Tadesse, H., Blake, A. J., Champness, N. R., Warren, J. E., Rizkallah, P. and Licence, P. 2012. Supramolecular architectures of symmetrical dicationic ionic liquid based systems. Crystengcomm 14(15), pp. 4886-4893. (10.1039/c2ce25106j)
- Lane, S. W., Dennis, C. A., Lane, C. L., Trinh, C. H., Rizkallah, P., Stockley, P. G. and Phillips, S. E. V. 2011. Construction and crystal structure of recombinant STNV capsids. Journal of Molecular Biology 413(1), pp. 41-50. (10.1016/j.jmb.2011.07.062)
- Miles, J. J. et al. 2010. Genetic and structural basis for selection of a ubiquitous T cell receptor deployed in Epstein-Barr virus infection. PLoS Pathogens 6(11), article number: e1001198. (10.1371/journal.ppat.1001198)
- Ronson, T. K., Carruthers, C., Fisher, J., Brotin, T., Harding, L. P., Rizkallah, P. and Hardie, M. J. 2010. Tripodal 4-pyridyl-derived host ligands and their metallo-supramolecular chemistry: stella octangula and bowl-shaped assemblies. Inorganic Chemistry -American Chemical Society- 49(2), pp. 675-685. (10.1021/ic901972h)
- Ronson, T. K., Fisher, J., Harding, L. P., Rizkallah, P., Warren, J. E. and Hardie, M. J. 2009. Stellated polyhedral assembly of a topologically complicated Pd4L4 'Solomon cube'. Nature Chemistry 1(3), pp. 212-216. (10.1038/nchem.213)
- Cole, D. et al. 2009. Germ line-governed recognition of a cancer epitope by an immunodominant human T-cell receptor. Journal of Biological Chemistry 284(40), article number: 27281-27289. (10.1074/jbc.M109.022509)
- Govada, L. et al. 2008. Crystal structure of the C1 domain of cardiac myosin binding protein-C: Implications for hypertrophic cardiomyopathy. Journal of Molecular Biology 378(2), pp. 387-397. (10.1016/j.jmb.2008.02.044)
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- Cole, D. et al. 2007. Computational design and crystal structure of an enhanced affinity mutant human CD8 αα coreceptor. Proteins: Structure, Function and Bioinformatics 67(1), pp. 65-74. (10.1002/prot.21176)
- Cole, D. et al. 2006. Crystal structure of HLA-A*2402 complexed with a telomerase peptide. European Journal of Immunology 36(1), pp. 170-179. (10.1002/eji.200535424)
- Cole, D. et al. 2005. Crystallization and preliminary X-ray structural studies of a high-affinity CD8αα co-receptor to pMHC. Acta Crystallographica Section F: Structural Biology and Crystallization Communications 61(3), pp. 285-287. (10.1107/S1744309105002988)
Research
- Adenovirus Modulation for Oncotherapy: We have subverted the natural adenovirus pathogen to be a delivery vehicle for cancer specific epitopes that can raise immunity against these cancers. The virus is first rendered non-proliferative by removing the replication exons, then a short stretch of coding nucleotides are inserted at a strategic point in the targetting protein on the sruface of the virus to mimic part of the cancer associated protein. When the target cells are infected, the epitope is expressed and the immune system is mobilised to recognise it, attacking all malignant cells. We have used structure determination extensively to gain information about the best strategy to employ in this effort, with around 20 new entries into the protein data bank. Collaboration with the group of Prof Alan Parker at the School of Medicine, Cardiff University.
- Immune System Proteins: This work aims to determine the structural factors involved in the cross-reactivity of Thymus-derived cell receptors, TCRs, when they recognise more than one antigen presented in the context of the Major Histocompatibility complex, a mechanism underlying autoimmunity. A second aspect is the degeneracy of TCR binding to various antigens presented by one MHC to allow wide coverage of possible antigens with the limited number of MHCs an individual has. The project involves using X-ray crystallography for solving 3D structures of these entities, and conducting binding studies with surface plasmon resonance, isothermal titration calorimetry and naive T-cell activation. Colaboration with the T-cell Modulation Group led by Prof Andrew Sewell, in the Institute of Infection and Immunology, Cardiff University.
- Enhanced Green Fuorescent Proteins: The green fluorescent protein from Aequoris victoria is currently used in many biological and biotechnological applications to aid in mapping the distribution of biological entities in cells, via attaching it to antibodies raised against molecules of interest. Upon binding, the GFP carrying antibody fluoresces at specific wavelengths. A program of genetic engineering of the GFP from the jelly fish Aequoria victoria aims to enhance its fluorescence properties for better visibility. Collaboration with Dr Dafydd Jones in the School of Biosciences at Cardiff University.
- Natural Bacterial Insecticidal Toxins: We are studying various natural toxins produced by Bacillus thuringiensis and similar organisms to understand their mode of action and to develop environmentally friendly pesticides that can be targetted at specific pests. Collaboration with Prof Colin Berry in the School of Bioscineces at Cardiff University.
- Calpain Inhibitor Design: Calpain is a multi-domain caspase involved in response to inflammation. It helps white blood cells change shape to cross through epithelial tissue near inflammation sites. Too much activity is associated with arthrhitis after heightened response level. Inhibition of Domain VI had been achieved in the past, elsewhere, working with the porcine enzyme. Here, we are working on the human enzyme, trying to optimise the inhibitor for higher affinity and improved recognition. Collaboration with a team led by Prof Ruedi Allemann in the School of Chemistry, Cardiff University.
- Biocoloration in lobster shell: The structure of β-crystacyanin, the coloured protein in lobster shell, was solved using softer X-rays to phase diffraction data. The structure delineated the mechanism by which light is abosrbed and modulated by the protein to effect a different emission in the visible spectrum by influencing the conformation of the astaxanthin chromophore bound by the protein. New methodology was developed to use the anomalous signal from S atoms in order to solve the structure. Collaboration with Prof John Helliwell, Manchester Unversity.
- Carbohydrate Recognition: Binding of carbohydrate substrates by various lectins was studied in this project. The mode of binding of oligomaric mannose branches by monocot lectins and sucrose binding by legime lectins were studied. Collaboration with Prof Colin Reynolds, Liverpool John Moores University.
- Snake Venom Proteins: The a-neurotoxin of the kign cobra Naja kaouthia and the haemorragin of Bothrops jararaca were studied in collaboration with Prof RDG Theakston, Liverpool School of Tropical Medicine.
Teaching
- Introduction to Structural Biology module in Bioinformatics MSc course
- Structural Biology for Medical undergraduates, as student selected component
- Mentoring undergraduate Medical students
Biography
Education
- 1984: PhD Chemistry, Nottingham University, UK
- 1979: BSc Chemistry, Lebanese University, Beirut, Lebanon
Career Overview
- Senior Lecturer / RCUK Senior Fellow, Cardiff University, since Dec 2008
- Protein Crystallography Facility Manager, Synchrotron Radiation Source, Daresbury, UK. 19 Feb 1990 - 30 Sep 2008
- Higher Scientific Officer, Agriculture and Food Research Council, Reading, UK. 2 Jan - 15 Feb 1990
- Senior Research Fellow, Liverpool University and Daresbury Laboratory, UK. 1 Nov 1987- 31 Dec 1989
- Post Doctoral Research Assistant, Leeds University, UK. 1 Dec 1984 - 30 Sep 1987
- Production Line Manager, International Cosmetics Manufacturers S.A.L., Beirut, Lebanon. 1 Sep 1979 - 31 Aug 1980
Committees
- Treasurer, Biologicsl Structures Group of the British Crystallographic Association, 2008-2017
- Scientific Advisers Committee, SESAME Synchrotron project, Middle East, 2000-2004
- Synchrotron Radiation Users Forum, 1997-2007
- Secretary to the Beamtime Allocation Panel, SRS Daresbury, 1990-1995
Supervisions
New funding as co-supervisor for a student, starting in October 2021, to study adenoviruses.
Engagement
Cardiff University Structural Biology Network
Coordinating meetings to discuss matters related to the topic of Structural Biology. Presentations by visiting scientists or members of Cardiff University.
Cardiff University Beamtime Allocation Group at Diamond
Coordinating access to the facilities at the Diamond Light Source National Facility at Harwell, for X-ray crystallography, Small Angle X-ray Scattering, Circular Dichroism spectroscopy, Biological Imaging, etc.