Dr John M. Sanderson
(email at firstname.lastname@example.org)
Dr John M Sanderson has research interests in Biophysical Chemistry, with a particular emphasis on biological membranes. He is a committee member of the British Biophysical Society, and a member of the Biophysical Society (US) and the Royal Society of Chemistry (MRSC). Research expertise in the group includes amino acid and peptide synthesis, liposome technology and techniques for studying biological membranes, including surface tensiometry, calorimetry, x-ray scattering, optical microscopy and mass spectrometry. Current work is directed towards the study of protein-membrane interactions over all timescales and the preparation of asymmetric lipid membranes for biophysical studies of membrane activity (funded by an EPSRC programme grant).
Work encompasses the design of peptides that have the potential to form stable pores in lipid membranes, the characterisation of peptide interactions with membrane lipids and the physical organic chemistry of peptide reactions in membranes. Particular interests include the kinetics of peptide rearrangements following membrane binding1 and the chemical stability of peptide-lipid systems. Recent work has begun to establish the factors that control the innate reactivity of peptides towards acyl transfer from membrane lipids (intrinsic lipidation).2
Membrane Protein Chemistry
The behaviour of membrane proteins in membranes is being examined using a range of analytical approaches. Post-translational modifications to aquaporin-0 are being examined by mass spectrometry and reveal a diverse lipidation profile at each of the two lipidation sites of the protein (with Prof. R. A. Quinlan, Biological Sciences, Durham University). The membrane-binding properties of proteins from enveloped viruses are being characterised by a combination of microscopy, chemical biology and structral biology approaches (with Dr R. P. Yeo, Biological Sciences, Durham University). This has led to the structure determination for RSV M protein (in collaboration with Dr V. Money),3 and studies of membrane bindign using tensiometry, electron microscopy, circular dichroism and Brewster angle microscopy.4
Amino Acid and Drug-Lipid Interactions
We have used host-guest chemistry5 to test the hypothesis that aromatic amino acids have thermodynamically significant interactions with the headgroups of neutral lipids such as phosphatidylcholines. In the case of the Tryptophan and Tyrosine, we have demonstrated that both preferentially form 2:1 adducts with lipids. Using NMR and modelling approaches, we have been able to rationalise the adducts formed between Tryptophan and phosphocholine headgroups in terms of the intermolecular interactions involved. Current work is examining the chemistry exhibited by drug molecules after their adsorbtion to lipid membranes.
Spectroscopy and Microscopy of Lipid Membranes
Current work centres around the synthesis and exploitation of labelled lipids and sterols.6 In previous work we demonstrated the generation of Raman spectra from individual trapped liposomes and the use of Scanning Electrochemical Microscopy (SECM) to observe redox switching of a modified gramicidin channel (with Dr R. Kataky, Durham University). Brewster angle microscopy has been used to characterise the association of peripheral membrane proteins with lipid monolayers (with Dr A Beeby, Durham University).4
- Catherine J. Pridmore, Alison Rodger and John M. Sanderson, Biochim. Biophys. Acta, 2016, 1858, 892–903.
- Robert H. Dods, Burkhard Bechinger, Jackie A. Mosely and John M. Sanderson, J. Mol. Biol., 2013, 425, 4379–4387.
- Victoria A. Money, Helen K. McPhee, Jackie A. Mosely, John M. Sanderson and Robert P. Yeo, Proc. Natl. Acad. Sci. U. S. A., 2009, 106, 4441–4446.
- Helen K. McPhee, Jennifer L. Carlisle, Andrew Beeby, Victoria A. Money, Scott M. D. Watson, Robert P. Yeo and John M. Sanderson, Langmuir, 2011, 27, 304–311.
- Georg Blaser, John M. Sanderson and Mark R. Wilson, Org. Biomol. Chem., 2009, 7, 5119–5128.
- Celia de la Calle Arregui, Jonathan A. Purdie, Catherine A. Haslam, Robert V. Law and John M. Sanderson, Chem. Phys. Lipids, 2016, 195, 58–62
- 1: Sanderson, John M (2020). Far From Inert: Membrane Lipids Possess Intrinsic Reactivity That Has Consequences For Cell Biology. BioEssays 42(3): 1900147.
- 2: Britt, Hannah M. , Prakash, Aruna S. , Appleby, Sanna , Mosely, Jackie A. & Sanderson, John M. (2020). Lysis of Membrane Lipids Promoted by Small Organic Molecules: Reactivity Depends on Structure but not Lipophilicity. Science Advances 6(17): eaaz8598.
- 3: Britt, Hannah M., García-Herrero, Clara A., Denny, Paul W., Mosely, Jackie A. & Sanderson, John M. (2019). Lytic reactions of drugs with lipid membranes. Chemical Science 10(3): 674-680.
- 4: Britt, Hannah M., Mosely, Jackie A. & Sanderson, John M. (2019). The Influence of Cholesterol on Melittin Lipidation in Neutral Membranes. Physical Chemistry Chemical Physics 21(2): 631-640.
- 5: Pridmore, Catherine J., Rodger, Alison & Sanderson, John M. (2016). The Association of Defensin HNP-2 with Negatively Charged Membranes: A Combined Fluorescence and Linear Dichroism Study. Biochimica et Biophysica Acta (BBA) - Biomembranes 1858(4): 892-903.
- 6: Ismail, Vian S., Mosely, Jackie A., Tapodi, Antal Quinlan, Roy A. & Sanderson, John M. (2016). The Lipidation Profile of Aquaporin-0 Correlates with The Acyl Composition of Phosphoethanolamine Lipids in Lens Membranes. Biochimica et Biophysica Acta (BBA) - Biomembranes 1858(11): 2763-2768.
- 7: de la Calle Arregui, Celia, Purdie, Jonathan A., Haslam, Catherine A., Law, Robert V. & Sanderson, John M. (2016). Optimised conditions for the synthesis of 17O and 18O labelled cholesterol. Chemistry and Physics of Lipids 195: 58-62.
- 8: Dods, RH Bechinger, B Mosely, JA & Sanderson, JM (2013). Acyl Transfer from Membrane Lipids to Peptides Is a Generic Process. Journal of Molecular Biology 425(22): 4379–4387.
- 9: Dods, RH, Mosely, JA & Sanderson, JM (2012). The innate reactivity of a membrane associated peptide towards lipids: acyl transfer to melittin without enzyme catalysis. Organic & Biomolecular Chemistry 10(28): 5371-5378.
- 10: Sanderson, John M (2012). Resolving the kinetics of lipid, protein and peptide diffusion in membranes. Molecular Membrane Biology 29(5): 118–143.
- 11: Ennaceur, Sue M. , Hicks, Matthew R. Pridmore, Catherine J. , Dafforn, Tim R. Rodger, Alison. & Sanderson, John M. (2009). Peptide Adsorption to Lipid Bilayers: Slow Processes Revealed by Linear Dichroism Spectroscopy. Biophysical Journal 96(4): 1399-1407.
- 12: Money, V.A. McPhee, H.K. Mosely, J.A., Sanderson, J.M. & Yeo, R.P. (2009). Surface features of a Mononegavirales matrix protein indicate sites of membrane interaction. Proceedings of the National Academy of Sciences, USA 106(11): 4441-4446.