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Dr Fabio Parmeggiani
(he/him)
Lecturer, EPSRC early career fellow
School of Pharmacy and Pharmaceutical Sciences
- Available for postgraduate supervision
Overview
My group works at the intersection between experimental and computational biology to develop novel diagnostic and therapeutic proteins, and new methods for protein engineering and selection. We combine state of the art computational tools for protein design, both physics-based and machine learning, with protein expression and characterization.
Research areas
Modular protein design: making proteins by adding and swapping validated building blocks
Carbohydrate binding: designing novel proteins to recognize sugars, oligosaccharides and glycans
Rigid and dynamic protein structures: design for controlled movement
Antimicrobial resistance: designing proteins to overcome biofilm resistance to treatments
Open positions
We are always looking for undergraduates, postgraduates and postdoc interested in protein design, both from experimental and computational/mathematical backgrounds.
Currently available:
1 PhD student position on protein design for carbohydrate recognition and antimicrobial applications, available via GW4 MRC DTP starting in September 2025, in collaboration with Dr Angela Nobbs (University of Bristol). Application deadline: Monday 4th November 2024. Info and application here.
Publication
2024
- Zelenka, N. R. et al. 2024. Data hazards in synthetic biology. Synthetic Biology 9(1), article number: ysae010. (10.1093/synbio/ysae010)
- Moreno-Tortolero, R. O. et al. 2024. Molecular organization of fibroin heavy chain and mechanism of fibre formation in Bombyx mori. Communications Biology 7, article number: 786. (10.1038/s42003-024-06474-1)
- Sarvaharman, S., Neary, T. E., Gorochowski, T. E. and Parmeggiani, F. 2024. Scalable design of repeat protein structural dynamics via probabilistic coarse-grained models. [Online]. medRxiv. (10.1101/2024.03.13.584748) Available at: https://doi.org/10.1101/2024.03.13.584748
2023
- Bethel, N. et al. 2023. Precisely patterned nanofibres made from extendable protein multiplexes. Nature Chemistry 15(Decemb), pp. 1664-1671. (10.1038/s41557-023-01314-x)
- Moreno-Tortolero, R. et al. 2023. Silk road revealed: Mechanism of silk fibre formation inBombyx mori. [Online]. bioRxiv: Cold Spring Harbor Laboratory. (10.1101/2023.06.02.543394) Available at: https://doi.org/10.1101/2023.06.02.543394
2021
- Gidley, F. and Parmeggiani, F. 2021. Repeat proteins: designing new shapes and functions for solenoid folds. Current Opinion in Structural Biology 68, pp. 208-214. (10.1016/j.sbi.2021.02.002)
2020
- Yeh, C., Obendorf, L. and Parmeggiani, F. 2020. Elfin UI. Frontiers in Bioengineering and Biotechnology 8, article number: 568318. (10.3389/fbioe.2020.568318)
2018
- Geiger-Schuller, K., Sforza, K., Yuhas, M., Parmeggiani, F., Baker, D. and Barrick, D. 2018. Extreme stability in de novo-designed repeat arrays is determined by unusually stable short-range interactions. Proceedings of the National Academy of Sciences 115(29), pp. 7539-7544. (10.1073/pnas.1800283115)
- Yeh, C., Brunette, T., Baker, D., McIntosh-Smith, S. and Parmeggiani, F. 2018. Elfin: An algorithm for the computational design of custom three-dimensional structures from modular repeat protein building blocks. Journal of Structural Biology X 201(2), pp. 100-107. (10.1016/j.jsb.2017.09.001)
2017
- Parmeggiani, F. and Huang, P. 2017. Designing repeat proteins. Current Opinion in Structural Biology 45(8), pp. 116-123. (10.1016/j.sbi.2017.02.001)
2016
- Mills, J. et al. 2016. Computational design of a homotrimeric metalloprotein with a trisbipyridyl core. Proceedings of the National Academy of Sciences 113(52), pp. 15012-15017. (10.1073/pnas.1600188113)
- Fallas, J. et al. 2016. Computational design of self-assembling cyclic protein homo-oligomers. Nature Chemistry 9(4), pp. 353-360. (10.1038/nchem.2673)
2015
- Brunette, T. et al. 2015. Exploring the repeat protein universe through computational protein design. Nature 528(7583), pp. 580-584. (10.1038/nature16162)
- Doyle, L., Hallinan, J., Bolduc, J., Parmeggiani, F., Baker, D., Stoddard, B. and Bradley, P. 2015. Rational design of alpha-helical tandem repeat proteins with closed architectures. Nature 528(7583), pp. 585-588. (10.1038/nature16191)
- Huang, P., Feldmeier, K., Parmeggiani, F., Velasco, D., Hoecker, B. and Baker, D. 2015. De novo design of a four-fold symmetric TIM-barrel protein with atomic-level accuracy. Nature Chemical Biology 12(1), pp. 29-34. (10.1038/nchembio.1966)
- Park, K., Shen, B. W., Parmeggiani, F., Huang, P. S., Stoddard, B. and Baker, D. 2015. Control of repeat-protein curvature by computational protein design. Nature Structural and Molecular Biology 22(2), pp. 167-174. (10.1038/nsmb.2938)
2014
- Parmeggiani, F. et al. 2014. A general computational approach for repeat protein design. Journal of Molecular Biology 427(2), pp. 563-575. (10.1016/j.jmb.2014.11.005)
2013
- Prindle, M., Schmitt, M., Parmeggiani, F. and Loeb, L. 2013. A substitution in the fingers domain of DNA polymerase delta reduces fidelity by altering nucleotide discrimination in the catalytic site. Journal of Biological Chemistry 288(8), pp. 5572-5580. (10.1074/jbc.M112.436410)
2012
- Baxter, S. et al. 2012. Engineering domain fusion chimeras from I-OnuI family LAGLIDADG homing endonucleases. Nucleic Acids Research 40(16), pp. 7985-8000. (10.1093/nar/gks502)
- Alfarano, P. et al. 2012. Optimization of designed armadillo repeat proteins by molecular dynamics simulations and NMR spectroscopy. Protein Science 21(9), pp. 1298-1314. (10.1002/pro.2117)
- Reichen, C. et al. 2012. Design and Selection of Armadillo Repeat Proteins: A novel technology for modular peptide recognition. Protein Science 21(Supple), pp. 82.
2008
- Parmeggiani, F. et al. 2008. Designed armadillo repeat proteins as general peptide-binding scaffolds: Consensus design and computational optimization of the hydrophobic core. Journal of Molecular Biology 376(5), pp. 1282-1304. (10.1016/j.jmb.2007.12.014)
2007
- Radeghieri, A., Bonoli, M., Parmeggiani, F. and Hochkoeppler, A. 2007. Tyrosine83 is essential for the activity of E-coli galactoside transacetylase. Biochimica Et Biophysica Acta-Proteins and Proteomics 1774(2), pp. 243-248. (10.1016/j.bbapap.2006.11.013)
- Navratilova, I. et al. 2007. Thermodynamic benchmark study using Biacore technology. Analytical Biochemistry 364(1), pp. 67-77. (10.1016/j.ab.2007.01.031)
Articles
- Zelenka, N. R. et al. 2024. Data hazards in synthetic biology. Synthetic Biology 9(1), article number: ysae010. (10.1093/synbio/ysae010)
- Moreno-Tortolero, R. O. et al. 2024. Molecular organization of fibroin heavy chain and mechanism of fibre formation in Bombyx mori. Communications Biology 7, article number: 786. (10.1038/s42003-024-06474-1)
- Bethel, N. et al. 2023. Precisely patterned nanofibres made from extendable protein multiplexes. Nature Chemistry 15(Decemb), pp. 1664-1671. (10.1038/s41557-023-01314-x)
- Gidley, F. and Parmeggiani, F. 2021. Repeat proteins: designing new shapes and functions for solenoid folds. Current Opinion in Structural Biology 68, pp. 208-214. (10.1016/j.sbi.2021.02.002)
- Yeh, C., Obendorf, L. and Parmeggiani, F. 2020. Elfin UI. Frontiers in Bioengineering and Biotechnology 8, article number: 568318. (10.3389/fbioe.2020.568318)
- Geiger-Schuller, K., Sforza, K., Yuhas, M., Parmeggiani, F., Baker, D. and Barrick, D. 2018. Extreme stability in de novo-designed repeat arrays is determined by unusually stable short-range interactions. Proceedings of the National Academy of Sciences 115(29), pp. 7539-7544. (10.1073/pnas.1800283115)
- Yeh, C., Brunette, T., Baker, D., McIntosh-Smith, S. and Parmeggiani, F. 2018. Elfin: An algorithm for the computational design of custom three-dimensional structures from modular repeat protein building blocks. Journal of Structural Biology X 201(2), pp. 100-107. (10.1016/j.jsb.2017.09.001)
- Parmeggiani, F. and Huang, P. 2017. Designing repeat proteins. Current Opinion in Structural Biology 45(8), pp. 116-123. (10.1016/j.sbi.2017.02.001)
- Mills, J. et al. 2016. Computational design of a homotrimeric metalloprotein with a trisbipyridyl core. Proceedings of the National Academy of Sciences 113(52), pp. 15012-15017. (10.1073/pnas.1600188113)
- Fallas, J. et al. 2016. Computational design of self-assembling cyclic protein homo-oligomers. Nature Chemistry 9(4), pp. 353-360. (10.1038/nchem.2673)
- Brunette, T. et al. 2015. Exploring the repeat protein universe through computational protein design. Nature 528(7583), pp. 580-584. (10.1038/nature16162)
- Doyle, L., Hallinan, J., Bolduc, J., Parmeggiani, F., Baker, D., Stoddard, B. and Bradley, P. 2015. Rational design of alpha-helical tandem repeat proteins with closed architectures. Nature 528(7583), pp. 585-588. (10.1038/nature16191)
- Huang, P., Feldmeier, K., Parmeggiani, F., Velasco, D., Hoecker, B. and Baker, D. 2015. De novo design of a four-fold symmetric TIM-barrel protein with atomic-level accuracy. Nature Chemical Biology 12(1), pp. 29-34. (10.1038/nchembio.1966)
- Park, K., Shen, B. W., Parmeggiani, F., Huang, P. S., Stoddard, B. and Baker, D. 2015. Control of repeat-protein curvature by computational protein design. Nature Structural and Molecular Biology 22(2), pp. 167-174. (10.1038/nsmb.2938)
- Parmeggiani, F. et al. 2014. A general computational approach for repeat protein design. Journal of Molecular Biology 427(2), pp. 563-575. (10.1016/j.jmb.2014.11.005)
- Prindle, M., Schmitt, M., Parmeggiani, F. and Loeb, L. 2013. A substitution in the fingers domain of DNA polymerase delta reduces fidelity by altering nucleotide discrimination in the catalytic site. Journal of Biological Chemistry 288(8), pp. 5572-5580. (10.1074/jbc.M112.436410)
- Baxter, S. et al. 2012. Engineering domain fusion chimeras from I-OnuI family LAGLIDADG homing endonucleases. Nucleic Acids Research 40(16), pp. 7985-8000. (10.1093/nar/gks502)
- Alfarano, P. et al. 2012. Optimization of designed armadillo repeat proteins by molecular dynamics simulations and NMR spectroscopy. Protein Science 21(9), pp. 1298-1314. (10.1002/pro.2117)
- Reichen, C. et al. 2012. Design and Selection of Armadillo Repeat Proteins: A novel technology for modular peptide recognition. Protein Science 21(Supple), pp. 82.
- Parmeggiani, F. et al. 2008. Designed armadillo repeat proteins as general peptide-binding scaffolds: Consensus design and computational optimization of the hydrophobic core. Journal of Molecular Biology 376(5), pp. 1282-1304. (10.1016/j.jmb.2007.12.014)
- Radeghieri, A., Bonoli, M., Parmeggiani, F. and Hochkoeppler, A. 2007. Tyrosine83 is essential for the activity of E-coli galactoside transacetylase. Biochimica Et Biophysica Acta-Proteins and Proteomics 1774(2), pp. 243-248. (10.1016/j.bbapap.2006.11.013)
- Navratilova, I. et al. 2007. Thermodynamic benchmark study using Biacore technology. Analytical Biochemistry 364(1), pp. 67-77. (10.1016/j.ab.2007.01.031)
Websites
- Sarvaharman, S., Neary, T. E., Gorochowski, T. E. and Parmeggiani, F. 2024. Scalable design of repeat protein structural dynamics via probabilistic coarse-grained models. [Online]. medRxiv. (10.1101/2024.03.13.584748) Available at: https://doi.org/10.1101/2024.03.13.584748
- Moreno-Tortolero, R. et al. 2023. Silk road revealed: Mechanism of silk fibre formation inBombyx mori. [Online]. bioRxiv: Cold Spring Harbor Laboratory. (10.1101/2023.06.02.543394) Available at: https://doi.org/10.1101/2023.06.02.543394
Research
We are an interdisciplinary group that brings together computational design and experimental characterization of proteins. We employ state of the art software (e.g. AlphaFold, Rosetta, RFdiffusion) and develop new tools (Elfin, CLIMBS) to solve challenging problems by designing the right protein for the job.
Modular protein design
We work on designing novel proteins with custom structures, using well characterized building blocks that can be fused through known interfaces and Elfin, a software for modular assembly we have designed. The process allows to achieve high success rate experimentally. We used these modular structures, based on natural and designed repeat proteins, to build custom nanoparticles with multiple embedded functions for cell recognition and activation by clustering and co-clustering of receptors.
Carbohydrate binding
We have developed a machine learning software, CLIMBS, for recognition and ranking of carbohydrate binding, as alternative to energy-based score functions. CLIMBS can efficiently identify native-like binders, and we are using it to evaluate results of molecular docking and guide design of novel carbohydrate binding proteins as novel potential diagnostics and therapeutics.
Rigid and dynamic protein structures
We have developed computational methods to rapidly evaluate the dynamics and available conformations of modular proteins. we are using these tools to design novel proteins with specific motions, and switch between closed and open conformations under specific conditions, such as environmental changes and recognition of targets. This has potential applications in the design of nanoparticle for drug delivery and biosensors.
Current group members
Fabio Parmeggiani (PI)
Yijie (Jacky) Luo (PhD student, with Woolfson group, University of Bristol)
Srikanth Lingappa (PhD student, with Berger group, University of Bristol)
Pierpaolo Foddai (MSc student)
Collaborators
Ash Toye (University of Bristol): cell surface receptor binding
Louis Luk (Cardiff University): design of D-proteins
Angela Nobbs (University of Bristol): antimicrobials for biofilms
Imre Berger (University of Bristol): engineering of snake venom proteins for vaccine production
Biography
I am a lecturer at the Cardiff School of Pharmacy & Pharmaceutical Sciences since 2024. I obtained my Ph.D. in Biochemistry from the University of Zurich working in the group of Andreas Pluckthun, then joined the group of David Baker at the University of Washington to work on computational protein design and became group leader and EPSRC early career research fellow at the University of Bristol, before joining Cardiff University. I have worked at the forefront of experimental and computational protein engineering and design and I am currently developing new methods to design proteins with modular structures, evaluating protein dynamics during design, and designing new proteins to recognize carbohydrates, both as cell surface antigens and in bacterial biofilms. The goal is to apply these tools for the development of new diagnostics and therapeutics.
Professional memberships
Rosetta Commons https://rosettacommons.org/
Biochemical Society https://www.biochemistry.org/
Academic positions
Lecturer, School of Parmacy and Pahrmaceutical Sciences, Cardiff University (2024-)
Research Fellow, School of Chemistry and School of Biochemistry, University of Bristol (2016-2024)
Postdoctoral Research Fellow and Acting Instructor, Department of Biochemistry and Institute for Protein Design, University of Washington (2009-2016)
Contact Details
Research themes
Specialisms
- Biochemistry
- Protein design and engineering
- Nanobiotechnology
- Bioinformatics and computational biology
- Characterisation of biological macromolecules