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Dr Jonathan Phillips

Dr Jonathan Phillips

Senior Research 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

Living Systems Institute Profile

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.

*We also have the potential to support two internships this summer*

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

Grants/Funding

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

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

Lautenschläger J, Stephens AD, Fusco G, Ströhl F, Curry N, Zacharopoulou M, Michel CH, Laine R, Nespovitaya N, Fantham M, et al (In Press). 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). Full text.
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.  Full text.
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.  Full text.
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). Full text.
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

Lautenschläger J, Stephens AD, Fusco G, Ströhl F, Curry N, Zacharopoulou M, Michel CH, Laine R, Nespovitaya N, Fantham M, et al (In Press). C-terminal calcium binding of α-synuclein modulates synaptic vesicle interaction. Nat Commun, 9(1). Abstract.  Author URL.

2018

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). Full text.
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.  Full text.
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.  Full text.
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). Full text.

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 2018-12-15 08:37:35

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Teaching

Supervision / Group

Postgraduate researchers

  • Zacharopoulou Maria (MPhil student at University of Cambridge)
  • Carolina Orozco (Joint PhD student with Dr Sophie Jackson, University of Cambridge)

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