![Dafydd Jones](https://profiles-cardiff.imgix.net/attachments/1079?w=200&h=200&auto=format&crop=faces&fit=crop&q=90")
Yr Athro Dafydd Jones
Athro
Ysgol y Biowyddorau
- JonesDD@caerdydd.ac.uk
- +44 29208 74290
- Adeilad Syr Martin Evans, Ystafell Cardiff School of Biosciences, Main Building, Museum Avenue, Cardiff, CF10 3AT, Rhodfa'r Amgueddfa, Caerdydd, CF10 3AX
- Sylwebydd y cyfryngau
- Ar gael fel goruchwyliwr ôl-raddedig
Trosolwyg
Research overview
The main focus of the Jones group is the structural and functional plasticity of proteins. Our research involves the study and engineering of a variety of protein systems, with a focus on fluorescent proteins and antibiotic resistance systems. Much of the group's work lies at the interface between biology, chemistry and physics and has a basis in the protein side of synthetic biology whereby we construct new proteins components, new scaffolds and bionanohybrid systems. We have a particualr interest in introducing new chemistry into proteins throught the use of expanded genetic code approaches and interfacing proteins in a designed manner with nano-materials to generate for protein-gated nanodevices and biomolecular electronics. We have also developed several transposon-based methods for the directed evolution of proteins using non-homologous recombination. The groups uses a variety of approaches including computational design, rational protein engineering and directed evolution with structural biology, single molecule analysis, moleculart dynamics, biophysics and biochemical techniques used to investigate the properties of these novel proteins.
Resources
Here is a link to my PyMOL Tutorial <<<<<
News
New paper published in Chemical Science providing details on how one of the most widely used protein tools in the life sciences, fluorescent proteins, synthesis their chromophore so giving them the useful properties. Great international collaboration with Alexander Nemukhin (Russia), Igor Alabugin (USA), Gabe Gomes (Canada) and Pierre Rizkallah (Cardiff) bringing together synthetic biology, structural biology, biophysics, chemical mechanisms and computionatal simulations.
Highly competitive EPSRC New Horizons grant awarded for developing genetically encoded far red/IR probes for new bioimaging approaches. Excellent collaboration with Paola Borri, Wolfgang Langbein and Pete Watson.
New paper out in Advanced Science highlighting that we need to pay closer attention how fluorescent protein fusion constructs are produced.
New paper in Chem Comm on how we combined an engineered a small haem binding protein to activate the fluoresence of a key by-product of anemia.
New paper in Bioconjugate Chemistry outlining how we can use light to attach proteins in a very defined manner to carbon nanotubes.
Our review written by Rebecca Gywther on the importance of protein oligomers as a new route to generating artifical protein systems is available to read here.
Cyhoeddiad
2024
- Grigorenko, B. L., Khrenova, M., Jones, D. D. and Nemukhin, A. 2024. Histidine-assisted reduction of arylnitrenes upon photo-activation of phenyl azide chromophores in the GFP-like fluorescent proteins. Organic and Biomolecular Chemistry 22, pp. 337-347. (10.1039/D3OB01450A)
2023
- Mack, A. H., Menzies, G., Southgate, A., Jones, D. D., Connor, T. R. and Leitner, T. 2023. A proofreading mutation with an allosteric effect allows a cluster of SARS-CoV-2 viruses to rapidly evolve. Molecular Biology and Evolution 40(10), article number: msad209. (10.1093/molbev/msad209)
- Evans, O., Singh, V., Aksakal, O., Jones, D., Borri, P. and Langbein, W. 2023. Low-temperature plasmonically enhanced single-molecule spectroscopy of fluorescent proteins. Presented at: The European Conference on Lasers and Electro-Optics 2023, 26-30 June 20232023 Conference on Lasers and Electro-Optics Europe & European Quantum Electronics Conference (CLEO/Europe-EQEC). IEEE, (10.1109/cleo/europe-eqec57999.2023.10231465)
- Ramakrishnan, K. et al. 2023. Glycosylation increases active site rigidity leading to improved enzyme stability and turnover. The FEBS Journal 290(15), pp. 3812-3827. (10.1111/febs.16783)
- Stano, P., Altamura, E., Mavelli, F., Singh, V. and Jones, D. D. 2023. Editorial: Fiat lux! Light-driven and light-controlled synthetic biological parts, devices, systems and processes. Frontiers in Bioengineering and Biotechnology 11, article number: 1201962. (10.3389/fbioe.2023.1201962)
- Zitti, A. and Jones, D. 2023. Expanding the genetic code: a non-natural amino acid story. Biochemist 45(1), pp. 2-6. (10.1042/bio_2023_102)
- Ahmed, R. D., Auhim, H. S., Worthy, H. L. and Jones, D. D. 2023. Fluorescent proteins: Crystallization, structural determination, and nonnatural amino acid incorporation. In: Sharma, M. ed. Fluorescent Proteins: Methods and Protocols., Vol. 2564. Methods in Molecular Biology Springer, pp. 99-119., (10.1007/978-1-0716-2667-2_5)
2022
- Lee, C., Gwyther, R. E., Freeley, M., Jones, D. and Palma, M. 2022. Fabrication and functionalisation of nanocarbon-based field-effect transistor biosensors. ChemBioChem 23(23), article number: e202200282. (10.1002/cbic.202200282)
- Cervantes-Salguero, K., Freeley, M., Gwyther, R. E. A., Jones, D. D., Chavez, J. L. and Palma, M. 2022. Single molecule DNA origami nanoarrays with controlled protein orientation. Biophysics Reviews 3(3) (10.1063/5.0099294)
- Gwyther, R. E. A., Nekrasov, N. P., Emilianov, A. V., Nasibulin, A. G., Ramakrishnan, K., Bobrinetskiy, I. and Jones, D. D. 2022. Differential bio-optoelectronic gating of semiconducting carbon nanotubes by varying the covalent attachment residue of a green fluorescent protein. Advanced Functional Materials 32(22), article number: 2112374. (10.1002/adfm.202112374)
- 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)
- Xu, X. et al. 2021. Tuning electrostatic gating of semiconducting carbon nanotubes by controlling protein orientation in biosensing devices. Angewandte Chemie International Edition 60(37), pp. 20184-20189. (10.1002/anie.202104044)
- Johnson, R. L., Blaber, H. G., Evans, T., Worthy, H. L., Pope, J. R. and Jones, D. D. 2021. Designed artificial protein heterodimers with coupled functions constructed using bio-orthogonal chemistry. Frontiers in Chemistry 9, article number: 733550. (10.3389/fchem.2021.733550)
- Freeley, M., Gwyther, R. E. A., Jones, D. D. and Palma, M. 2021. DNA-directed assembly of carbon nanotube-protein hybrids. Biomolecules 11(7), article number: 955. (10.3390/biom11070955)
- Sabah Auhim, H. et al. 2021. Stalling chromophore synthesis of the fluorescent protein Venus reveals the molecular basis of the final oxidation step. Chemical Science 12(22), pp. 7735-7745. (10.1039/D0SC06693A)
- Worthy, H. L. et al. 2021. The crystal sructure of Bacillus cereus HblL1. Toxins 13(4), article number: 253. (10.3390/toxins13040253)
- 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
- Karuna, A. et al. 2020. Quantitative imaging of B1 cyclin expression across the cell cycle using green fluorescent protein tagging and epi-fluorescence. Cytometry Part A 97(10), pp. 1066-1072. (10.1002/cyto.a.24038)
- Bowen, B. J., McGarrity, A. R., Szeto, J. A., Pudney, C. R. and Jones, D. D. 2020. Switching protein metalloporphyrin binding specificity by design from iron to fluorogenic zinc. Chemical Communications 56(31), pp. 4308-4311. (10.1039/D0CC00596G)
- Thomas, S. K. et al. 2020. Site-specific protein photochemical covalent attachment to carbon nanotube side walls and its electronic impact on single molecule function. Bioconjugate Chemistry 31(3), pp. 584-594. (10.1021/acs.bioconjchem.9b00719)
2019
- Gwyther, R. E., Jones, D. D. and Worthy, H. L. 2019. Better together: building protein oligomers naturally and by design. Biochemical Society Transactions 47(6), pp. 1773-1780. (10.1042/BST20190283)
- 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)
- Gulácsy, C. E. et al. 2019. Excitation-energy-dependent molecular beacon detects early stage neurotoxic Aβ aggregates in the presence of cortical neurons. ACS Chemical Neuroscience 10(3), pp. 1240-1250. (10.1021/acschemneuro.8b00322)
2018
- Zaki, A. et al. 2018. Defined covalent assembly of protein molecules on graphene using a genetically encoded photochemical reaction handle. RSC Advances 8, pp. 5768-5775. (10.1039/c7ra11166e)
- Elliott, M. and Jones, D. D. 2018. Approaches to single molecule studies of metalloprotein electron transfer using scanning probe-based techniques. Biochemical Society Transactions 46(1), pp. 1-9. (10.1042/BST20170229)
- Halliwell, L. M., Jathoul, A. P., Bate, J. P., Worthy, H. L., Anderson, J. C., Jones, D. D. and Murray, J. A. H. 2018. ΔFlucs: brighter photinus pyralis firefly luciferases identified by surveying consecutive single amino acid deletion mutations in a thermostable variant. Biotechnology and Bioengineering 115(1), pp. 50-59. (10.1002/bit.26451)
2017
- Freeley, M. et al. 2017. Site-specific one-to-one click coupling of single proteins to individual carbon nanotubes: a single-molecule approach. Journal of the American Chemical Society 139(49), pp. 17834-17840. (10.1021/jacs.7b07362)
- Marth, G. et al. 2017. Precision templated bottom-up multiprotein nanoassembly through defined click chemistry linkage to DNA. ACS Nano 11(5), pp. 5003-5010. (10.1021/acsnano.7b01711)
2016
- 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)
2015
- Hartley, A. M. et al. 2015. Functional modulation and directed assembly of an enzyme through designed non-natural post-translation modification. Chemical Science 6(7), pp. 3712-3717. (10.1039/C4SC03900A)
- Arpino, J. A. J., Baldwin, A. J., McGarrity, A. R., Tippmann, E. M. and Jones, D. D. 2015. In-frame amber stop codon replacement mutagenesis for the directed evolution of proteins containing non-canonical amino acids: identification of residues open to bio-orthogonal modification. PLoS ONE 10(5), article number: e0127504. (10.1371/journal.pone.0127504)
- Rohamare, S., Gaikwad, S., Jones, D., Bhavnani, V., Pal, J., Sharma, R. and Chatterjee, P. 2015. Cloning, expression and in silico studies of a serine protease from a marine actinomycete (Nocardiopsis sp. NCIM 5124). Process Biochemistry 50(3), pp. 378-387. (10.1016/j.procbio.2014.12.025)
- Reddington, S. C., Baldwin, A. J., Thompson, R., Brancale, A., Tippmann, E. M. and Jones, D. D. 2015. Directed evolution of GFP with non-natural amino acids identifies residues for augmenting and photoswitching fluorescence. Chemical Science 6(2), pp. 1159-1166. (10.1039/C4SC02827A)
- 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
- Jones, D. D., Arpino, J. A. J., Baldwin, A. J. and Edmundson, M. C. 2014. Transposon-based approaches for generating novel molecular diversity during directed evolution. In: Gillam, E. M. J., Copp, J. M. and Ackerley, D. eds. Directed Evolution Library Creation: Methods and Protocols., Vol. 1179. Methods in Molecular Biology Springer, pp. 159-172., (10.1007/978-1-4939-1053-3_11)
- 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)
- 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
- 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)
- Morris, J. L., Reddington, S. C., Murphy, D. M., Jones, D. D., Platts, J. A. and Tippmann, E. M. 2013. Aryl azide photochemistry in defined protein environments. Organic Letters 15(4), pp. 728-731. (10.1021/ol3028779)
- 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
- Della Pia, E. A., Macdonald, J. E., Elliott, M. and Jones, D. D. 2012. Direct binding of a redox protein for single-molecule electron transfer measurements. Small 8(15), pp. 2341-2344. (10.1002/smll.201102416)
- Arpino, J. et al. 2012. Structural basis for efficient chromophore communication and energy transfer in a constructed didomain protein scaffold. Journal of the American Chemical Society 134(33), pp. 13632-13640. (10.1021/ja301987h)
- Della Pia, E. A., Elliott, M., Jones, D. D. and Macdonald, J. E. 2012. Orientation-dependent electron transport in a single redox protein [RETRACTED]. ACS Nano 6(1), pp. 355-361. (10.1021/nn2036818)
- Reddington, S. C., Tippmann, E. M. and Jones, D. D. 2012. Residue choice defines efficiency and influence of bioorthogonal protein modification via genetically encoded strain promoted Click chemistry. Chemical Communications 48(67), pp. 8419-8421. (10.1039/c2cc31887c)
- 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)
- Gamble, M. D., Kunze, G., Brancale, A., Wilson, K. S. and Jones, D. D. 2012. The role of substrate specificity and metal binding in defining the activity and structure of an intracellular subtilisin. FEBS Open Bio 2, pp. 209-215. (10.1016/j.fob.2012.07.001)
- Della Pia, E. A., Chi, Q., Macdonald, J. E., Ulstrup, J., Jones, D. D. and Elliott, M. 2012. Fast electron transfer through a single molecule natively structured redox protein. Nanoscale 4(22), pp. 7106-7113. (10.1039/c2nr32131a)
- Della Pia, E. A., Chi, Q., Elliott, M., Macdonald, J. E., Ulstrup, J. and Jones, D. D. 2012. Redox tuning of cytochrome b562 through facile metal porphyrin substitution. Chemical Communications 48(86), pp. 10624-10626. (10.1039/c2cc34302a)
2011
- Jones, D. D. 2011. Recombining low homology, functionally rich regions of bacterial subtilisins by combinatorial fragment exchange. PLoS ONE 6(9), article number: e24319. (10.1371/journal.pone.0024319)
- Gamble, M. D., Kunze, G., Dodson, E. J., Wilson, K. S. and Jones, D. D. 2011. Regulation of an intracellular subtilisin protease activity by a short propeptide sequence through an original combined dual mechanism. Proceedings of the National Academy of Sciences 108(9), pp. 3536-3541. (10.1073/pnas.1014229108)
- Della Pia, E. A., Chi, Q., Jones, D. D., Macdonald, J. E., Ulstrup, J. and Elliott, M. 2011. Single-molecule mapping of long-range electron transport for a cytochrome b562 variant. Nano Letters 11(1), pp. 176-182. (10.1021/nl103334q)
2010
- Vevodova, J., Gamble, M. D., Kunze, G., Ariza, A., Dodson, E., Jones, D. D. and Wilson, K. S. 2010. Crystal structure of an intracellular subtilisin reveals novel structural features unique to this subtilisin family. Structure 18(6), pp. 744-755. (10.1016/j.str.2010.03.008)
- Edwards, W. R., Williams, A. J., Morris, J. L., Baldwin, A. J., Allemann, R. K. and Jones, D. D. 2010. Regulation of β-Lactamase activity by remote binding of Heme: functional coupling of unrelated proteins through domain insertion. Biochemistry 49(31), pp. 6541-6549. (10.1021/bi100793y)
2009
- Baldwin, A. J., Arpino, J. A., Edwards, W. R., Tippmann, E. M. and Jones, D. D. 2009. Expanded chemical diversity sampling through whole protein evolution. Molecular Biosystems 5(7), pp. 764-766. (10.1039/B904031E)
- Stott, K. M., Yusof, A. M., Perham, R. N. and Jones, D. D. 2009. A Surface Loop Directs Conformational Switching of a Lipoyl Domain Between a Folded and a Novel Misfolded Structure. Structure 17(8), pp. 1117-1127. (10.1016/j.str.2009.07.001)
2008
- Baldwin, A. J., Busse, K., Simm, A. M. and Jones, D. D. 2008. Expanded molecular diversity generation during directed evolution by trinucleotide exchange (TriNEx). Nucleic Acids Research 36(13), article number: e77. (10.1093/nar/gkn358)
- Meltzer, M. et al. 2008. Allosteric activation of HtrA protease DegP by stress signals during bacterial protein quality control. Angewandte Chemie - International Edition 47(7), pp. 1332-1334. (10.1002/anie.200703273)
- Edwards, W. R., Busse, K., Allemann, R. K. and Jones, D. D. 2008. Linking the functions of unrelated proteins using a novel directed evolution domain insertion method. Nucleic Acids Research 36(13) (10.1093/nar/gkn363)
- Jones, D. D. and Perham, R. N. 2008. The role of loop and β-turn residues as structural and functional determinants for the lipoyl domain from the Escherichia coli 2-oxoglutarate dehydrogenase complex. Biochemical Journal 409, pp. 357-366. (10.1042/BJ20071119)
2007
- Jones, D. D. and Perham, R. N. 2007. The role of loop and β-turn residues as structural and functional determinants for the lipoyl domain from the Escherichia coli 2-oxoglutarate dehydrogenase complex. Biochemical Journal 409, pp. 357-366. (10.1042/BJ20071119)
- Simm, A. M., Baldwin, A. J., Busse, K. and Jones, D. D. 2007. Investigating protein structural plasticity by surveying the consequence of an amino acid deletion from TEM-1 β-lactamase. FEBS Letters 581(21), pp. 3904-3908. (10.1016/j.febslet.2007.07.018)
2005
- Jones, D. D. and Barker, P. 2005. Controlling self-assembly by linking protein folding, DNA binding and the redox chemistry of heme. Angewandte Chemie International Edition, pp. 6337-6341. (10.1002/anie.200463035)
- Jones, D. D. 2005. Triplet nucleotide removal at random positions in a target gene: the tolerance of TEM-1 β-lactamase to an amino acid deletion. Nucleic Acids Research 33(9) (10.1093/nar/gni077)
2004
- Jones, D. D. and Barker, P. D. 2004. Design and characterisation of an artificial DNA-binding cytochrome. ChemBioChem 5(7), pp. 964-971. (10.1002/cbic.200300569)
2002
- Perham, R. N., Jones, D. D., Chauhan, H. J. and Howard, M. J. 2002. Substrate channelling in 2-oxo acid dehydrogenase multienzyme complexes. Biochemical Society Transactions 30(2), pp. 47–51. (10.1042/0300-5127:0300047)
2001
- Jones, D. D., Perham, R., Reche, P. and Stott, K. 2001. Recognition of the lipoyl domain is the ultimate determinant of substrate channelling in the pyruvate dehydrogenase multienzyme complex. Journal of Molecular Biology, pp. 49-60. (10.1006/jmbi.2000.4257)
2000
- Jones, D. D., Stott, K. M., Howard, M. J. and Perham, R. N. 2000. Restricted motion of the lipoyl-lysine swinging arm in the pyruvate dehydrogenase complex of Escherichia coli†,‡. Biochemistry 39(29), pp. 8448–8459. (10.1021/bi992978i)
- Jones, D., Horne, H., Reche, P. A. and Perham, R. N. 2000. Structural determinants of post-translational modification and catalytic specificity for the lipoyl domains of the pyruvate dehydrogenase multienzyme complex of Escherichia coli. Journal of Molecular Biology 295(2), pp. 289-306. (10.1006/jmbi.1999.3335)
Articles
- Grigorenko, B. L., Khrenova, M., Jones, D. D. and Nemukhin, A. 2024. Histidine-assisted reduction of arylnitrenes upon photo-activation of phenyl azide chromophores in the GFP-like fluorescent proteins. Organic and Biomolecular Chemistry 22, pp. 337-347. (10.1039/D3OB01450A)
- Mack, A. H., Menzies, G., Southgate, A., Jones, D. D., Connor, T. R. and Leitner, T. 2023. A proofreading mutation with an allosteric effect allows a cluster of SARS-CoV-2 viruses to rapidly evolve. Molecular Biology and Evolution 40(10), article number: msad209. (10.1093/molbev/msad209)
- Ramakrishnan, K. et al. 2023. Glycosylation increases active site rigidity leading to improved enzyme stability and turnover. The FEBS Journal 290(15), pp. 3812-3827. (10.1111/febs.16783)
- Stano, P., Altamura, E., Mavelli, F., Singh, V. and Jones, D. D. 2023. Editorial: Fiat lux! Light-driven and light-controlled synthetic biological parts, devices, systems and processes. Frontiers in Bioengineering and Biotechnology 11, article number: 1201962. (10.3389/fbioe.2023.1201962)
- Zitti, A. and Jones, D. 2023. Expanding the genetic code: a non-natural amino acid story. Biochemist 45(1), pp. 2-6. (10.1042/bio_2023_102)
- Lee, C., Gwyther, R. E., Freeley, M., Jones, D. and Palma, M. 2022. Fabrication and functionalisation of nanocarbon-based field-effect transistor biosensors. ChemBioChem 23(23), article number: e202200282. (10.1002/cbic.202200282)
- Cervantes-Salguero, K., Freeley, M., Gwyther, R. E. A., Jones, D. D., Chavez, J. L. and Palma, M. 2022. Single molecule DNA origami nanoarrays with controlled protein orientation. Biophysics Reviews 3(3) (10.1063/5.0099294)
- Gwyther, R. E. A., Nekrasov, N. P., Emilianov, A. V., Nasibulin, A. G., Ramakrishnan, K., Bobrinetskiy, I. and Jones, D. D. 2022. Differential bio-optoelectronic gating of semiconducting carbon nanotubes by varying the covalent attachment residue of a green fluorescent protein. Advanced Functional Materials 32(22), article number: 2112374. (10.1002/adfm.202112374)
- 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)
- Xu, X. et al. 2021. Tuning electrostatic gating of semiconducting carbon nanotubes by controlling protein orientation in biosensing devices. Angewandte Chemie International Edition 60(37), pp. 20184-20189. (10.1002/anie.202104044)
- Johnson, R. L., Blaber, H. G., Evans, T., Worthy, H. L., Pope, J. R. and Jones, D. D. 2021. Designed artificial protein heterodimers with coupled functions constructed using bio-orthogonal chemistry. Frontiers in Chemistry 9, article number: 733550. (10.3389/fchem.2021.733550)
- Freeley, M., Gwyther, R. E. A., Jones, D. D. and Palma, M. 2021. DNA-directed assembly of carbon nanotube-protein hybrids. Biomolecules 11(7), article number: 955. (10.3390/biom11070955)
- Sabah Auhim, H. et al. 2021. Stalling chromophore synthesis of the fluorescent protein Venus reveals the molecular basis of the final oxidation step. Chemical Science 12(22), pp. 7735-7745. (10.1039/D0SC06693A)
- Worthy, H. L. et al. 2021. The crystal sructure of Bacillus cereus HblL1. Toxins 13(4), article number: 253. (10.3390/toxins13040253)
- 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)
- Karuna, A. et al. 2020. Quantitative imaging of B1 cyclin expression across the cell cycle using green fluorescent protein tagging and epi-fluorescence. Cytometry Part A 97(10), pp. 1066-1072. (10.1002/cyto.a.24038)
- Bowen, B. J., McGarrity, A. R., Szeto, J. A., Pudney, C. R. and Jones, D. D. 2020. Switching protein metalloporphyrin binding specificity by design from iron to fluorogenic zinc. Chemical Communications 56(31), pp. 4308-4311. (10.1039/D0CC00596G)
- Thomas, S. K. et al. 2020. Site-specific protein photochemical covalent attachment to carbon nanotube side walls and its electronic impact on single molecule function. Bioconjugate Chemistry 31(3), pp. 584-594. (10.1021/acs.bioconjchem.9b00719)
- Gwyther, R. E., Jones, D. D. and Worthy, H. L. 2019. Better together: building protein oligomers naturally and by design. Biochemical Society Transactions 47(6), pp. 1773-1780. (10.1042/BST20190283)
- 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)
- Gulácsy, C. E. et al. 2019. Excitation-energy-dependent molecular beacon detects early stage neurotoxic Aβ aggregates in the presence of cortical neurons. ACS Chemical Neuroscience 10(3), pp. 1240-1250. (10.1021/acschemneuro.8b00322)
- Zaki, A. et al. 2018. Defined covalent assembly of protein molecules on graphene using a genetically encoded photochemical reaction handle. RSC Advances 8, pp. 5768-5775. (10.1039/c7ra11166e)
- Elliott, M. and Jones, D. D. 2018. Approaches to single molecule studies of metalloprotein electron transfer using scanning probe-based techniques. Biochemical Society Transactions 46(1), pp. 1-9. (10.1042/BST20170229)
- Halliwell, L. M., Jathoul, A. P., Bate, J. P., Worthy, H. L., Anderson, J. C., Jones, D. D. and Murray, J. A. H. 2018. ΔFlucs: brighter photinus pyralis firefly luciferases identified by surveying consecutive single amino acid deletion mutations in a thermostable variant. Biotechnology and Bioengineering 115(1), pp. 50-59. (10.1002/bit.26451)
- Freeley, M. et al. 2017. Site-specific one-to-one click coupling of single proteins to individual carbon nanotubes: a single-molecule approach. Journal of the American Chemical Society 139(49), pp. 17834-17840. (10.1021/jacs.7b07362)
- Marth, G. et al. 2017. Precision templated bottom-up multiprotein nanoassembly through defined click chemistry linkage to DNA. ACS Nano 11(5), pp. 5003-5010. (10.1021/acsnano.7b01711)
- 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)
- Hartley, A. M. et al. 2015. Functional modulation and directed assembly of an enzyme through designed non-natural post-translation modification. Chemical Science 6(7), pp. 3712-3717. (10.1039/C4SC03900A)
- Arpino, J. A. J., Baldwin, A. J., McGarrity, A. R., Tippmann, E. M. and Jones, D. D. 2015. In-frame amber stop codon replacement mutagenesis for the directed evolution of proteins containing non-canonical amino acids: identification of residues open to bio-orthogonal modification. PLoS ONE 10(5), article number: e0127504. (10.1371/journal.pone.0127504)
- Rohamare, S., Gaikwad, S., Jones, D., Bhavnani, V., Pal, J., Sharma, R. and Chatterjee, P. 2015. Cloning, expression and in silico studies of a serine protease from a marine actinomycete (Nocardiopsis sp. NCIM 5124). Process Biochemistry 50(3), pp. 378-387. (10.1016/j.procbio.2014.12.025)
- Reddington, S. C., Baldwin, A. J., Thompson, R., Brancale, A., Tippmann, E. M. and Jones, D. D. 2015. Directed evolution of GFP with non-natural amino acids identifies residues for augmenting and photoswitching fluorescence. Chemical Science 6(2), pp. 1159-1166. (10.1039/C4SC02827A)
- 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)
- 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)
- 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)
- 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)
- Morris, J. L., Reddington, S. C., Murphy, D. M., Jones, D. D., Platts, J. A. and Tippmann, E. M. 2013. Aryl azide photochemistry in defined protein environments. Organic Letters 15(4), pp. 728-731. (10.1021/ol3028779)
- 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)
- Della Pia, E. A., Macdonald, J. E., Elliott, M. and Jones, D. D. 2012. Direct binding of a redox protein for single-molecule electron transfer measurements. Small 8(15), pp. 2341-2344. (10.1002/smll.201102416)
- Arpino, J. et al. 2012. Structural basis for efficient chromophore communication and energy transfer in a constructed didomain protein scaffold. Journal of the American Chemical Society 134(33), pp. 13632-13640. (10.1021/ja301987h)
- Della Pia, E. A., Elliott, M., Jones, D. D. and Macdonald, J. E. 2012. Orientation-dependent electron transport in a single redox protein [RETRACTED]. ACS Nano 6(1), pp. 355-361. (10.1021/nn2036818)
- Reddington, S. C., Tippmann, E. M. and Jones, D. D. 2012. Residue choice defines efficiency and influence of bioorthogonal protein modification via genetically encoded strain promoted Click chemistry. Chemical Communications 48(67), pp. 8419-8421. (10.1039/c2cc31887c)
- 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)
- Gamble, M. D., Kunze, G., Brancale, A., Wilson, K. S. and Jones, D. D. 2012. The role of substrate specificity and metal binding in defining the activity and structure of an intracellular subtilisin. FEBS Open Bio 2, pp. 209-215. (10.1016/j.fob.2012.07.001)
- Della Pia, E. A., Chi, Q., Macdonald, J. E., Ulstrup, J., Jones, D. D. and Elliott, M. 2012. Fast electron transfer through a single molecule natively structured redox protein. Nanoscale 4(22), pp. 7106-7113. (10.1039/c2nr32131a)
- Della Pia, E. A., Chi, Q., Elliott, M., Macdonald, J. E., Ulstrup, J. and Jones, D. D. 2012. Redox tuning of cytochrome b562 through facile metal porphyrin substitution. Chemical Communications 48(86), pp. 10624-10626. (10.1039/c2cc34302a)
- Jones, D. D. 2011. Recombining low homology, functionally rich regions of bacterial subtilisins by combinatorial fragment exchange. PLoS ONE 6(9), article number: e24319. (10.1371/journal.pone.0024319)
- Gamble, M. D., Kunze, G., Dodson, E. J., Wilson, K. S. and Jones, D. D. 2011. Regulation of an intracellular subtilisin protease activity by a short propeptide sequence through an original combined dual mechanism. Proceedings of the National Academy of Sciences 108(9), pp. 3536-3541. (10.1073/pnas.1014229108)
- Della Pia, E. A., Chi, Q., Jones, D. D., Macdonald, J. E., Ulstrup, J. and Elliott, M. 2011. Single-molecule mapping of long-range electron transport for a cytochrome b562 variant. Nano Letters 11(1), pp. 176-182. (10.1021/nl103334q)
- Vevodova, J., Gamble, M. D., Kunze, G., Ariza, A., Dodson, E., Jones, D. D. and Wilson, K. S. 2010. Crystal structure of an intracellular subtilisin reveals novel structural features unique to this subtilisin family. Structure 18(6), pp. 744-755. (10.1016/j.str.2010.03.008)
- Edwards, W. R., Williams, A. J., Morris, J. L., Baldwin, A. J., Allemann, R. K. and Jones, D. D. 2010. Regulation of β-Lactamase activity by remote binding of Heme: functional coupling of unrelated proteins through domain insertion. Biochemistry 49(31), pp. 6541-6549. (10.1021/bi100793y)
- Baldwin, A. J., Arpino, J. A., Edwards, W. R., Tippmann, E. M. and Jones, D. D. 2009. Expanded chemical diversity sampling through whole protein evolution. Molecular Biosystems 5(7), pp. 764-766. (10.1039/B904031E)
- Stott, K. M., Yusof, A. M., Perham, R. N. and Jones, D. D. 2009. A Surface Loop Directs Conformational Switching of a Lipoyl Domain Between a Folded and a Novel Misfolded Structure. Structure 17(8), pp. 1117-1127. (10.1016/j.str.2009.07.001)
- Baldwin, A. J., Busse, K., Simm, A. M. and Jones, D. D. 2008. Expanded molecular diversity generation during directed evolution by trinucleotide exchange (TriNEx). Nucleic Acids Research 36(13), article number: e77. (10.1093/nar/gkn358)
- Meltzer, M. et al. 2008. Allosteric activation of HtrA protease DegP by stress signals during bacterial protein quality control. Angewandte Chemie - International Edition 47(7), pp. 1332-1334. (10.1002/anie.200703273)
- Edwards, W. R., Busse, K., Allemann, R. K. and Jones, D. D. 2008. Linking the functions of unrelated proteins using a novel directed evolution domain insertion method. Nucleic Acids Research 36(13) (10.1093/nar/gkn363)
- Jones, D. D. and Perham, R. N. 2008. The role of loop and β-turn residues as structural and functional determinants for the lipoyl domain from the Escherichia coli 2-oxoglutarate dehydrogenase complex. Biochemical Journal 409, pp. 357-366. (10.1042/BJ20071119)
- Jones, D. D. and Perham, R. N. 2007. The role of loop and β-turn residues as structural and functional determinants for the lipoyl domain from the Escherichia coli 2-oxoglutarate dehydrogenase complex. Biochemical Journal 409, pp. 357-366. (10.1042/BJ20071119)
- Simm, A. M., Baldwin, A. J., Busse, K. and Jones, D. D. 2007. Investigating protein structural plasticity by surveying the consequence of an amino acid deletion from TEM-1 β-lactamase. FEBS Letters 581(21), pp. 3904-3908. (10.1016/j.febslet.2007.07.018)
- Jones, D. D. and Barker, P. 2005. Controlling self-assembly by linking protein folding, DNA binding and the redox chemistry of heme. Angewandte Chemie International Edition, pp. 6337-6341. (10.1002/anie.200463035)
- Jones, D. D. 2005. Triplet nucleotide removal at random positions in a target gene: the tolerance of TEM-1 β-lactamase to an amino acid deletion. Nucleic Acids Research 33(9) (10.1093/nar/gni077)
- Jones, D. D. and Barker, P. D. 2004. Design and characterisation of an artificial DNA-binding cytochrome. ChemBioChem 5(7), pp. 964-971. (10.1002/cbic.200300569)
- Perham, R. N., Jones, D. D., Chauhan, H. J. and Howard, M. J. 2002. Substrate channelling in 2-oxo acid dehydrogenase multienzyme complexes. Biochemical Society Transactions 30(2), pp. 47–51. (10.1042/0300-5127:0300047)
- Jones, D. D., Perham, R., Reche, P. and Stott, K. 2001. Recognition of the lipoyl domain is the ultimate determinant of substrate channelling in the pyruvate dehydrogenase multienzyme complex. Journal of Molecular Biology, pp. 49-60. (10.1006/jmbi.2000.4257)
- Jones, D. D., Stott, K. M., Howard, M. J. and Perham, R. N. 2000. Restricted motion of the lipoyl-lysine swinging arm in the pyruvate dehydrogenase complex of Escherichia coli†,‡. Biochemistry 39(29), pp. 8448–8459. (10.1021/bi992978i)
- Jones, D., Horne, H., Reche, P. A. and Perham, R. N. 2000. Structural determinants of post-translational modification and catalytic specificity for the lipoyl domains of the pyruvate dehydrogenase multienzyme complex of Escherichia coli. Journal of Molecular Biology 295(2), pp. 289-306. (10.1006/jmbi.1999.3335)
Book sections
- Ahmed, R. D., Auhim, H. S., Worthy, H. L. and Jones, D. D. 2023. Fluorescent proteins: Crystallization, structural determination, and nonnatural amino acid incorporation. In: Sharma, M. ed. Fluorescent Proteins: Methods and Protocols., Vol. 2564. Methods in Molecular Biology Springer, pp. 99-119., (10.1007/978-1-0716-2667-2_5)
- Jones, D. D., Arpino, J. A. J., Baldwin, A. J. and Edmundson, M. C. 2014. Transposon-based approaches for generating novel molecular diversity during directed evolution. In: Gillam, E. M. J., Copp, J. M. and Ackerley, D. eds. Directed Evolution Library Creation: Methods and Protocols., Vol. 1179. Methods in Molecular Biology Springer, pp. 159-172., (10.1007/978-1-4939-1053-3_11)
Conferences
- Evans, O., Singh, V., Aksakal, O., Jones, D., Borri, P. and Langbein, W. 2023. Low-temperature plasmonically enhanced single-molecule spectroscopy of fluorescent proteins. Presented at: The European Conference on Lasers and Electro-Optics 2023, 26-30 June 20232023 Conference on Lasers and Electro-Optics Europe & European Quantum Electronics Conference (CLEO/Europe-EQEC). IEEE, (10.1109/cleo/europe-eqec57999.2023.10231465)
Ymchwil
The Jones group focus on understanding the molecular basis of protein plasticity in terms of structure, function and folding, and its application to the construction of new protein components and systems. The ultimate aim is to address one of the fundamental questions in biology: how amino acid sequence encodes the information for a protein to fold to its functional 3D structure. Our group collaborates chemists, structural biologists, computer modellers and physicists. Constructing new protein components means our work is closely aligned with the areas of synthetic biology and nanoscience/nanotechnology.
Protein structure, function, dynamics and engineering
The structure, function and folding of a range of proteins are investigated using biochemical, biophysical, structural biology and molecular dynamics. One of the main focuses of the group currently are fluorescent proteins, haem binding proteins and ß-lactam antimicrobial resistance systems. We also have an interest in various enzymes including the subtilisin serine proteases and cold-active esterases.
A full list of the structure determined by the group can be found here.
Construction of artificial protein scaffolds
The ability to design new proteins with activities not part of the natural repertoire is essential as part of the development of synthetic biology and bionanotechnology. As a general approach for creating tailored protein components with unique but useful properties, we couple the structures and hence functions of normally unrelated proteins or even non-protein materials so as to link the function. To achieve this, existing proteins will require radical redesign or even the creation of new scaffolds. However, natural proteins provide the inspiration and guidance during construction. One key aspect we aim for is synergy between different components so that one component “talks” to the other.
The group uses a variety of approaches to construct these new scaffold including: (1) domain insertion by directed evolution; (2) rational domain grafting; (3) linking proteins via click chemistry; (4) constructing bionanohybrids in which proteins are linked to secondary molecular systems such as DNA origami and nano-carbon.
We have recently successfully demonstrated designed interfacing of proteins to both the side-wall and end wall of nano-carbon systems using both light and click chemistry approaches. The two systems are functionally coupled due to the designed and intimate interface between the two molecular systems.
Single molecule studies of electron and energy transfer proteins
Electron and energy transfer plays a vital role in biology being pivotal to processes such as photosynthesis, respiration and enzyme catalysis. Such proteins essentially work at the single molecule but most approaches at analyse at the bulk level so all the important detail becomes averaged out. Furthermore, given that proteins self assemble, organise and modulate electron/energy transfer system at the single molecule, there is potential for the adaptation for use as nanodevices, including molecular transistors and biomolecular electronics. The Jones groups has been involved in interdisciplinary research collaborations aimed at investigating the single molecule behaviour these systems. Proteins are engineered for specific residues to allowed defined and precise interactions with conducting surface and materials. This has led to several important developments in the area of molecular electronics and single protein molecule studies. Notably, we have demonstrated for the first time direct coupling of a protein to both electrodes allowing ET to be monitored at the single molecule level.
Our studies revealed that cytochrome b562 was remarkably conductive and exhibited transistor-like behaviour with current modulated electrochemically. We have also shown that protein surfaces can electrostatically gate conductance through nano-carbon materials so paving the way for next-generation biosensors.
Engineering proteins using an expanded genetic code
We use an expanded genetic code to engineer proteins to contain new chemical diversity. The shared genetic code restricts most organisms to the incorporation of the same 20 amino acids into proteins, thus limiting the chemical functionality available. Expansion of the genetic code to allow the incorporation of potentially useful non-natural amino acids into a growing polypeptide chain in vivo will generate proteins with novel and enhanced physicochemical and biological properties not accessible in Nature. This in turn will provide new approaches for studying both the molecular and cellular aspect of protein function and for adapting proteins for biotechnological applications. The group are developing computational approaches to predict the effect of non-natural amino acid incorporation on protein function, and to use the new chemistry to adapt proteins for use in areas ranging from novel bioimaging approaches to bottom-up bionanohybrid assembly.
Transposon-based methods for directed evolution
We have also developed a range of transposon-based technologies to sample various different mutational events not normally sampled during directed evolution. The method can be used to insert or delete multiples of three nucleotides resulting in the in-frame deletion or insertion of amino acids at random positions in a protein. Indel mutations alter the structure and hence function of protein in ways not accessible to substitution mutations alone thus expanding the sequence, structure and functional space sampled by directed evolution. We have also extended these methods to allow the replacement of one trinucleotide sequence with another either predetermined (e.g. TAG) or random (e.g. NNN) sequence. This allows directed evolution to perform a "scanning mutagenesis" function and overcome the "codon bias" problems inherent with existing directed evolution methods. The transposon-based method has also been used to create new protein scaffolds by recombining two normally disparate, non-homologous proteins, so creating novel chimeric proteins.
Funding
- BBSRC
- EPSRC
- KESS
- MRC
- Wellcome Trust
- Commonwealth SC
Postgraduate research students
- Ms Rebecca Gwyther
- Ms Rochelle Ahmed
- Ms Athena Zitti
- Mr Ozan Aksakal
- Ms Lainey Williamson (2nd-supervisor).
Collaborations
Internal
- Profs Paola Borri (Biosciences) and Wolfgang Langbein (Physics) (new bioimaging approaches)
- Prof Colin Berry (insecticidal protein engineering and structural biology)
- Prof Emyr Macdonald (Single protein molecule ET - Physics)
- Dr Pierre Rizkallah (Protein structure determination – Medicine)
- Dr Oliver Castell (Single molecule fluoresence – Pharmacy)
- Dr Georgina Menzies (molecular dynamics - Biosciences)
External
- Dr Matteo Palma (QMUL). Bionanohybirds for conductance
- Dr Eugen Stulz (Southampton). Nanoscale assemblies
- Dr Chris Pudney (Bath). Protein dynamics and fluoresence.
- Dr Nehad Noby (Alexandria University, Egypt). Esterase structure and engineering
- Prof Alexander Nemukhin (Lomonosov Moscow State University, Russian Federation). QM/MM of fluorescent proteins.
Addysgu
Main teaching duties
1st Year. BI1001. Research Techniques
2nd Year. BI2232. Biochemistry.
3rd Year. BI3255. Synthetic Biology and Protein Engineering (Module lead). BI3001 - Final Year Project.
4th Year. BI4001. Advanced Reseach Project.
Bywgraffiad
Ar ôl ennill fy BSc mewn Biocemeg o Brifysgol Cymru, astudiais ar gyfer fy PhD mewn strwythur protein a pheirianneg ym Mhrifysgol Caergrawnt dan oruchwyliaeth yr Athro Richard Perham, gan dderbyn fy ngradd doethuriaeth ym 1999.
Mae fy ymchwil bellach wedi canolbwyntio ar strwythur protein a pheirianneg, ar ôl dal swyddi ymchwil yn y sectorau academaidd (Canolfan Peirianneg Protein MRC yng Nghaergrawnt a'r Adran Cemeg, Prifysgol Caergrawnt) a Chymrodoriaeth Ddiwydiannol Marie Curie yn Novozymes A / S Copenhagen, Denmarc). Symudais i Gaerdydd ym mis Medi 2003.
Rwyf wedi gwasanaethu ar banel thema Strwythur a Swyddogaeth Moleciwlaidd y Gymdeithas Biocemegol, gan drefnu dwy gynhadledd peirianneg protein lwyddiannus gan ddenu rhai o'r ymchwilwyr gorau o bob cwr o'r byd. Rwyf hefyd yn represenatives y DU o INPEC (International Network of Protein Engineering Centres).
Ymhlith fy ndyletswyddau addysgu amrywiol, rwy'n gydlynydd modiwl BI3255 (Bioleg synthetig a Pheirianneg Protein).
Meysydd goruchwyliaeth
Peirianneg protein, yn enwedig protein fflwroleuol
Adeiladu BioNanoHybrids defnyddiol lle mae protein yn gweithredu fel y lefel moleciwl sengl yn cael ei ddefnyddio i fodiwleiddio deunyddiau cynnal fel nano-carbon.
ymwrthedd gwrthficrobaidd.
Bioleg strwythurol ensym a dynameg.
Goruchwyliaeth gyfredol
Rochelle Ahmed
Myfyriwr ymchwil
Themâu ymchwil
Arbenigeddau
- Proteinau a peptidau
- Peirianneg foleciwlaidd feddygol asidau a phroteinau niwcleig
- Nanobiotechnoleg
- Biocemeg
- Dylunio a pheirianneg protein
