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Dr Jonathan Phillips

Dr Jonathan Phillips

UKRI Future Leaders Fellow

 7456

 +44 (0)1392 727456

 Living Systems Institute T04.14

 

Living Systems Institute, University of Exeter, Stocker Road, Exeter, EX4 4QD

Overview

I am interested in how molecules move, how this underpins important biological functions and ultimately how we can direct those dynamics to create new opportunities for medicine and biosensing.

My background is in protein biophysics – developing physical and chemical methods to gain insight into molecular structure, folding and dynamics. I have experience in studying naturally occurring proteins and also in synthetic biology – designing and building protein switches and self-assembly systems. These dual skillsets were ultimately brought together to study and engineer protein drugs and drug targets.

The research in my lab is focused on three interwoven threads:

  1. Studying the assembly and dynamics of protein systems in nature.
  2. Creating new molecular systems for medicine and biosensing.
  3. Advancing analytical methods to better understand protein dynamics.

Broad research specialisms

Biochemistry
Protein biophysics
Analytical chemistry
Mass spectrometry

Qualifications

2007 PhD Molecular Biophysics, Department of Chemistry, University of Cambridge

2000 BSc Medical Biochemistry, Department of Biochemistry, University of Birmingham

Research group links

Research

Research interests

I am interested in how molecules move, how this underpins important biological functions and ultimately how we can direct those dynamics to create new opportunities for medicine and biosensing.

My background is in protein biophysics – developing physical and chemical methods to gain insight into molecular structure, folding and dynamics. Much of this has been in what are termed ‘structural mass spectrometry’ techniques. The core approach used in my lab is hydrogen/deuterium-exchange mass spectrometry (HDX-MS), which is experiencing something of a renaissance: it has unique advantages in being able to measure protein structure, dynamics and thermodynamics (stability) in arbitrarily large systems (e.g. antibody dimers of 300 kDa), rapidly (<= seconds) and with single amino acid resolution. We are active in developing experimental and computational methods and tools to advance the scope of this powerful analytical technique.

I have experience in studying naturally occurring protein structure, folding and dynamics and also in synthetic biology – designing and building protein switches and self-assembly systems. These dual skillsets were first brought together in a biomedical context with an industrial fellowship to study and engineer protein drugs and drug targets. This momentum is continued at The Living Systems Institute as we investigate naturally occurring biological control and the potential to design conscious control of molecular systems.

The research in my lab is focused on three interwoven threads:

  1. Studying the assembly and dynamics of protein systems in nature.
  2. Creating new molecular systems for medicine and biosensing.
  3. Advancing analytical methods to better understand protein dynamics.

We welcome informal enquiries from prospective fellows and graduate students.

Research projects

  1. High-resolution antibody unfolding studies for developability and novel drug delivery
  2. Biopharmaceutical HOS analysis by automated fast hydrogen deuterium exchange
  3. Alpha synuclein structural dynamics ensemble in Parkinson’s disease mutants
  4. Botulinum neurotoxin stability and structural kinetics
  5. Mechanisms of helicase and nuclease enzymes in DNA damage repair
  6. The quantum robin: Cryptochrome protein as a magnetosensor

Grants/Funding

UKRI Future Leaders Fellowship: Protein Choreography

InnovateUK grant 102612: Biopharmaceutical HOS analysis by automated fast hydrogen deuterium exchange

MRC Proximity to Discovery: An adaptive sampling tool for the analysis of protein drugs

EPSRC DTP: The quantum robin: Cryptochrome protein as a magnetosensor

Ipsen: Botulinum neurotoxin stability and structural kinetics

Research grants

  • 2020 MRC
    Protein Choreography

Publications

Key publications | Publications by category | Publications by year

Publications by category

Books

Borisov OV (2016). State-of-the-art and Emerging Technologies for Therapeutic Monoclonal Antibody Characterization Defining the next generation of analytical and biophysical techniques., ACS Symposium. Abstract.

Journal articles

Kish M, Smith V, Subramanian S, Vollmer F, Lethbridge N, Cole L, Bond NJ, Phillips JJ (In Press). Allosteric regulation of glycogen phosphorylase solution phase structural dynamics at high spatial resolution.  Abstract.
Stephens AD, Zacharopoulou M, Moons R, Fusco G, Seetaloo N, Chiki A, Hooper PJ, Mela I, Lashuel HA, Phillips JJ, et al (In Press). Extent of N-terminus exposure by altered long-range interactions of monomeric alpha-synuclein determines its aggregation propensity.  Abstract.
Phillips J (In Press). Millisecond Hydrogen/Deuterium-Exchange Mass Spectrometry for the Study of Alpha-Synuclein Structural Dynamics under Physiological Conditions. Journal of Visualized Experiments Abstract.
Kish M, Subramanian S, Smith V, Lethbridge N, Cole L, Vollmer F, Bond NJ, Phillips JJ (2023). Allosteric Regulation of Glycogen Phosphorylase by Order/Disorder Transition of the 250′ and 280s Loops. Biochemistry, 62(8), 1360-1368.
Kish M, Smith V, Lethbridge N, Cole L, Bond NJ, Phillips JJ (2023). Online Fully Automated System for Hydrogen/Deuterium-Exchange Mass Spectrometry with Millisecond Time Resolution. Analytical Chemistry, 95(11), 5000-5008.
Guo Z, Parakra RD, Xiong Y, Johnston WA, Walden P, Edwardraja S, Moradi SV, Ungerer JPJ, Ai HW, Phillips JJ, et al (2022). Engineering and exploiting synthetic allostery of NanoLuc luciferase. Nature Communications, 13(1). Abstract.
Orozco CT, Bersellini M, Irving LM, Howard WW, Hargreaves D, Devine PWA, Siouve E, Browne GJ, Bond NJ, Phillips JJ, et al (2022). Mechanistic insights into the rational design of masked antibodies. mAbs, 14(1).
Seetaloo N, Zacharopoulou M, Stephens AD, Kaminski Schierle GS, Phillips JJ (2022). Millisecond Hydrogen/Deuterium-Exchange Mass Spectrometry Approach to Correlate Local Structure and Aggregation in α-Synuclein. Analytical Chemistry, 94(48), 16711-16719.
Seetaloo N, Phillips JJ (2022). Millisecond Hydrogen/Deuterium-Exchange Mass Spectrometry for the Study of Alpha-Synuclein Structural Dynamics under Physiological Conditions. Journal of Visualized Experiments, 2022(184). Abstract.
Orozco CT, Edgeworth MJ, Devine PWA, Hines AR, Cornwell O, Thompson C, Wang X, Phillips JJ, Ravn P, Jackson SE, et al (2021). Interconversion of Unexpected Thiol States Affects the Stability, Structure, and Dynamics of Antibody Engineered for Site-Specific Conjugation. Bioconjugate Chemistry, 32(8), 1834-1844.
Groves K, Ashcroft AE, Cryar A, Sula A, Wallace BA, Stocks BB, Burns C, Cooper-Shepherd D, De Lorenzi E, Rodriguez E, et al (2021). Reference Protocol to Assess Analytical Performance of Higher Order Structural Analysis Measurements: Results from an Interlaboratory Comparison. Anal Chem, 93(26), 9041-9048. Abstract.  Author URL.
Stephens AD, Zacharopoulou M, Moons R, Fusco G, Seetaloo N, Chiki A, Woodhams PJ, Mela I, Lashuel HA, Phillips JJ, et al (2020). Extent of N-terminus exposure of monomeric alpha-synuclein determines its aggregation propensity. Nature Communications, 11(1). Abstract.
Lautenschläger J, Stephens AD, Fusco G, Ströhl F, Curry N, Zacharopoulou M, Michel CH, Laine R, Nespovitaya N, Fantham M, et al (2018). C-terminal calcium binding of α-synuclein modulates synaptic vesicle interaction. Nat Commun, 9(1). Abstract.  Author URL.
Stephens AD, Nespovitaya N, Zacharopoulou M, Kaminski CF, Phillips JJ, Kaminski Schierle GS (2018). Different Structural Conformers of Monomeric α-Synuclein Identified after Lyophilizing and Freezing. Anal Chem, 90(11), 6975-6983. Abstract.  Author URL.
Phillips JJ, Buchanan A, Andrews J, Chodorge M, Sridharan S, Mitchell L, Burmeister N, Kippen AD, Vaughan TJ, Higazi DR, et al (2017). Rate of Asparagine Deamidation in a Monoclonal Antibody Correlating with Hydrogen Exchange Rate at Adjacent Downstream Residues. Analytical Chemistry, 89(4), 2361-2368.
Dobson CL, Devine PWA, Phillips JJ, Higazi DR, Lloyd C, Popovic B, Arnold J, Buchanan A, Lewis A, Goodman J, et al (2016). Engineering the surface properties of a human monoclonal antibody prevents self-association and rapid clearance in vivo. Scientific Reports, 6(1). Abstract.
Millership C, Phillips JJ, Main ERG (2016). Ising Model Reprogramming of a Repeat Protein's Equilibrium Unfolding Pathway. Journal of Molecular Biology, 428(9), 1804-1817. Abstract.
Edgeworth MJ, Phillips JJ, Lowe DC, Kippen AD, Higazi DR, Scrivens JH (2015). Global and Local Conformation of Human IgG Antibody Variants Rationalizes Loss of Thermodynamic Stability. Angew Chem Int Ed Engl, 54(50), 15156-15159. Abstract.  Author URL.
Klein T, Vajpai N, Phillips JJ, Davies G, Holdgate GA, Phillips C, Tucker JA, Norman RA, Scott AD, Higazi DR, et al (2015). Structural and dynamic insights into the energetics of activation loop rearrangement in FGFR1 kinase. Nature Communications, 6(1). Abstract.
Tavakoli-Keshe R, Phillips JJ, Turner R, Bracewell DG (2014). Understanding the relationship between biotherapeutic protein stability and solid-liquid interfacial shear in constant region mutants of IgG1 and IgG4. J Pharm Sci, 103(2), 437-444. Abstract.  Author URL.
Main ERG, Phillips JJ, Millership C (2013). Repeat protein engineering: creating functional nanostructures/biomaterials from modular building blocks. Biochem Soc Trans, 41(5), 1152-1158. Abstract.  Author URL.
Phillips JJ, Millership C, Main ERG (2012). Fibrous nanostructures from the self-assembly of designed repeat protein modules. Angew Chem Int Ed Engl, 51(52), 13132-13135. Abstract.  Author URL.
Phillips JJ, Javadi Y, Millership C, Main ERG (2012). Modulation of the multistate folding of designed TPR proteins through intrinsic and extrinsic factors. Protein Sci, 21(3), 327-338. Abstract.  Author URL.
Phillips JJ, Yao Z-P, Zhang W, McLaughlin S, Laue ED, Robinson CV, Jackson SE (2007). Conformational dynamics of the molecular chaperone Hsp90 in complexes with a co-chaperone and anticancer drugs. J Mol Biol, 372(5), 1189-1203. Abstract.  Author URL.

Conferences

Remmele RL, Bee JS, Phillips JJ, Mo WD, Higazi DR, Zhang J, Lindo V, Kippen AD (2015). Characterization of Monoclonal Antibody Aggregates and Emerging Technologies.  Abstract.

Publications by year

In Press

Kish M, Smith V, Subramanian S, Vollmer F, Lethbridge N, Cole L, Bond NJ, Phillips JJ (In Press). Allosteric regulation of glycogen phosphorylase solution phase structural dynamics at high spatial resolution.  Abstract.
Stephens AD, Zacharopoulou M, Moons R, Fusco G, Seetaloo N, Chiki A, Hooper PJ, Mela I, Lashuel HA, Phillips JJ, et al (In Press). Extent of N-terminus exposure by altered long-range interactions of monomeric alpha-synuclein determines its aggregation propensity.  Abstract.
Seetaloo N, Kish M, Phillips JJ (In Press). HDfleX: Software for flexible high structural resolution of hydrogen/deuterium-exchange mass spectrometry data.  Abstract.
Seetaloo N, Zacharopoulou M, Stephens AD, Kaminski Schierle GS, Phillips JJ (In Press). Local structural dynamics of alpha-synuclein correlate with aggregation in different physiological conditions.  Abstract.
Phillips J (In Press). Millisecond Hydrogen/Deuterium-Exchange Mass Spectrometry for the Study of Alpha-Synuclein Structural Dynamics under Physiological Conditions. Journal of Visualized Experiments Abstract.

2023

Kish M, Subramanian S, Smith V, Lethbridge N, Cole L, Vollmer F, Bond NJ, Phillips JJ (2023). Allosteric Regulation of Glycogen Phosphorylase by Order/Disorder Transition of the 250′ and 280s Loops. Biochemistry, 62(8), 1360-1368.
Kish M, Smith V, Lethbridge N, Cole L, Bond NJ, Phillips JJ (2023). Online Fully Automated System for Hydrogen/Deuterium-Exchange Mass Spectrometry with Millisecond Time Resolution. Analytical Chemistry, 95(11), 5000-5008.

2022

Guo Z, Parakra RD, Xiong Y, Johnston WA, Walden P, Edwardraja S, Moradi SV, Ungerer JPJ, Ai HW, Phillips JJ, et al (2022). Engineering and exploiting synthetic allostery of NanoLuc luciferase. Nature Communications, 13(1). Abstract.
Orozco CT, Bersellini M, Irving LM, Howard WW, Hargreaves D, Devine PWA, Siouve E, Browne GJ, Bond NJ, Phillips JJ, et al (2022). Mechanistic insights into the rational design of masked antibodies. mAbs, 14(1).
Seetaloo N, Zacharopoulou M, Stephens AD, Kaminski Schierle GS, Phillips JJ (2022). Millisecond Hydrogen/Deuterium-Exchange Mass Spectrometry Approach to Correlate Local Structure and Aggregation in α-Synuclein. Analytical Chemistry, 94(48), 16711-16719.
Seetaloo N, Phillips JJ (2022). Millisecond Hydrogen/Deuterium-Exchange Mass Spectrometry for the Study of Alpha-Synuclein Structural Dynamics under Physiological Conditions. Journal of Visualized Experiments, 2022(184). Abstract.

2021

Seetaloo N, Kish M, Phillips JJ (2021). HDfleX: Software for the flexible structural resolution of hydrogen-deuterium exchange mass spectrometry data.  Abstract.
Orozco CT, Edgeworth MJ, Devine PWA, Hines AR, Cornwell O, Thompson C, Wang X, Phillips JJ, Ravn P, Jackson SE, et al (2021). Interconversion of Unexpected Thiol States Affects the Stability, Structure, and Dynamics of Antibody Engineered for Site-Specific Conjugation. Bioconjugate Chemistry, 32(8), 1834-1844.
Groves K, Ashcroft AE, Cryar A, Sula A, Wallace BA, Stocks BB, Burns C, Cooper-Shepherd D, De Lorenzi E, Rodriguez E, et al (2021). Reference Protocol to Assess Analytical Performance of Higher Order Structural Analysis Measurements: Results from an Interlaboratory Comparison. Anal Chem, 93(26), 9041-9048. Abstract.  Author URL.

2020

Stephens AD, Zacharopoulou M, Moons R, Fusco G, Seetaloo N, Chiki A, Woodhams PJ, Mela I, Lashuel HA, Phillips JJ, et al (2020). Extent of N-terminus exposure of monomeric alpha-synuclein determines its aggregation propensity. Nature Communications, 11(1). Abstract.

2018

Lautenschläger J, Stephens AD, Fusco G, Ströhl F, Curry N, Zacharopoulou M, Michel CH, Laine R, Nespovitaya N, Fantham M, et al (2018). C-terminal calcium binding of α-synuclein modulates synaptic vesicle interaction. Nat Commun, 9(1). Abstract.  Author URL.
Stephens AD, Nespovitaya N, Zacharopoulou M, Kaminski CF, Phillips JJ, Kaminski Schierle GS (2018). Different Structural Conformers of Monomeric α-Synuclein Identified after Lyophilizing and Freezing. Anal Chem, 90(11), 6975-6983. Abstract.  Author URL.

2017

Phillips JJ, Buchanan A, Andrews J, Chodorge M, Sridharan S, Mitchell L, Burmeister N, Kippen AD, Vaughan TJ, Higazi DR, et al (2017). Rate of Asparagine Deamidation in a Monoclonal Antibody Correlating with Hydrogen Exchange Rate at Adjacent Downstream Residues. Analytical Chemistry, 89(4), 2361-2368.

2016

Dobson CL, Devine PWA, Phillips JJ, Higazi DR, Lloyd C, Popovic B, Arnold J, Buchanan A, Lewis A, Goodman J, et al (2016). Engineering the surface properties of a human monoclonal antibody prevents self-association and rapid clearance in vivo. Scientific Reports, 6(1). Abstract.
Millership C, Phillips JJ, Main ERG (2016). Ising Model Reprogramming of a Repeat Protein's Equilibrium Unfolding Pathway. Journal of Molecular Biology, 428(9), 1804-1817. Abstract.
Borisov OV (2016). State-of-the-art and Emerging Technologies for Therapeutic Monoclonal Antibody Characterization Defining the next generation of analytical and biophysical techniques., ACS Symposium. Abstract.

2015

Remmele RL, Bee JS, Phillips JJ, Mo WD, Higazi DR, Zhang J, Lindo V, Kippen AD (2015). Characterization of Monoclonal Antibody Aggregates and Emerging Technologies.  Abstract.
Edgeworth MJ, Phillips JJ, Lowe DC, Kippen AD, Higazi DR, Scrivens JH (2015). Global and Local Conformation of Human IgG Antibody Variants Rationalizes Loss of Thermodynamic Stability. Angew Chem Int Ed Engl, 54(50), 15156-15159. Abstract.  Author URL.
Klein T, Vajpai N, Phillips JJ, Davies G, Holdgate GA, Phillips C, Tucker JA, Norman RA, Scott AD, Higazi DR, et al (2015). Structural and dynamic insights into the energetics of activation loop rearrangement in FGFR1 kinase. Nature Communications, 6(1). Abstract.

2014

Tavakoli-Keshe R, Phillips JJ, Turner R, Bracewell DG (2014). Understanding the relationship between biotherapeutic protein stability and solid-liquid interfacial shear in constant region mutants of IgG1 and IgG4. J Pharm Sci, 103(2), 437-444. Abstract.  Author URL.

2013

Main ERG, Phillips JJ, Millership C (2013). Repeat protein engineering: creating functional nanostructures/biomaterials from modular building blocks. Biochem Soc Trans, 41(5), 1152-1158. Abstract.  Author URL.

2012

Phillips JJ, Millership C, Main ERG (2012). Fibrous nanostructures from the self-assembly of designed repeat protein modules. Angew Chem Int Ed Engl, 51(52), 13132-13135. Abstract.  Author URL.
Phillips JJ, Javadi Y, Millership C, Main ERG (2012). Modulation of the multistate folding of designed TPR proteins through intrinsic and extrinsic factors. Protein Sci, 21(3), 327-338. Abstract.  Author URL.

2007

Phillips JJ, Yao Z-P, Zhang W, McLaughlin S, Laue ED, Robinson CV, Jackson SE (2007). Conformational dynamics of the molecular chaperone Hsp90 in complexes with a co-chaperone and anticancer drugs. J Mol Biol, 372(5), 1189-1203. Abstract.  Author URL.

Jonathan_Phillips Details from cache as at 2023-06-08 16:55:51

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Teaching

Supervision / Group

Postgraduate researchers

  • Hannah Barnard (Joint PhD student with Prof. Geoff Nash and Dr Isaac Luxmoore, Dept. Engineering)
  • Heather Bottomley
  • Monika Kish Graduate Research Associate
  • Neeleema Seetaloo
  • Maria Zacharopoulou (PhD student at University of Cambridge with Dr Gabriele Kaminski Schierle)

Alumni

  • Denzel Gonzales
  • Carolina Orozco Now at AstraZeneca.(Previously joint PhD student with Dr Sophie Jackson, University of Cambridge)
  • Rinky Parakra
  • Laura Reffo ThermoFisher ScientificGraduated PhD with Dr Jonathan Phillips and Prof. Richard Chahwan (Univ. Zurich)

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