... understanding life in molecular detail

Prof Mike McPherson

Affimer artificial binding proteins; Protein expression and engineering, and directed evolution.


Research activity is focussed upon the use of our libraries of Affimer artificial binding proteins, previously called Adhiron. These can replace antibodies for most purposes and are small (ca 100 aa), robust (Tm >80 oC), easy to engineer and produce recombinantly. We use them for biomarker detection in research and biosensors, as tools for in vitor and vivo studies of protein-protein interactions,  as therapeutics, and imaging reagents. For example a major current focus is in the area of antimicrobial resistance. The lab is also engaged in enzyme engineering, often interfacing with Affimers.

Current major projects include:
  • Affimer binding proteins as antibody replacements
  • Protein engineering
  • Directed evolution
  • Antimicrobial resistance
  • Biosensors

Affimer artificial binding proteins as research tools and for diagnostics, imaging and therapy

We have developed a small stable protein scaffold and have generated high complexity libraries within variable regions  that create novel binding sites. These binding proteins, called Adhirons and also known as Affimers, are small, robust alternatives to antibodies. We use phage display to screen the libraries against a wide range of target molecules to identify specific binders. Affimers can be produced recombinantly and represent important tools for scientific investigations, essentially replacing antibodies with stable simple reagents. They can be used in applications such as biosensors, development of imaging reagents, as co-crystallization chaperones, to identify druggable sites, and as therapeutic agents.

For example, we generated Affimers against disease related biomarkers for incorporation into multiplex label-free electronic detection devices for clinical use. Affimers also be selected for other diagnostic applications including environmental, security or agricultural purposes. We use them as labelled reagents or coupled to quantum dots to detect various proteins in Western blots and tissue samples.

 We have used them in vivo where they can interfere with protein-protein interactions  to modulate protein function potentially identifying druggable sites.

I am Director of the Leeds Bioscreening Technology Group supported by the Leeds Biomedical Health Research Centre to provide a screening service for academics and clinicians and we undertake a range of collaborative projects with colleagues in Leeds, nationally and internationally.

 

Detailed research programme                  Close ▲

Selected Publications

  1. Robinson, JI, Baxter, EW, Owen, RL, Thomsen, M, Tomlinson, DC, Waterhouse, MP, Win, SJ, Nettleship, JE, Tiede, C, Foster, RJ, Owens, RJ, Fishwick, CWG, Harris, SA, Goldman, A, McPherson, MJ, Morgan, AW (2017) Affimers inhibit immune complex binding to FcγRIIIa with high specificity through competitive and allosteric modes of action. PNAS Plus, E72-81 doi/10.1073/pnas.1707856115, 2017.

     

  2. Tiede, C, Bedford, R, Heseltine, S, Smith, G, Wijetunga, I, Ross, R, Al-Qallaf, D, Roberts, A, Balls, A, Curd, A, Hughes, R, Martin, H, Needham, S, Zanetti-Domingues, L, Y. Sadigh, Peacock, T, Tang, A, Gibson, N, Kyle, H, Platt, G, Ingram, N, Taylor, T, Coletta, P, Manfield, I, Knowles, M, Bell, S, Esteves, F, Maqbool, A, Prasad, R, Drinkhill, D, Bon, R, Patel, V, Goodchild, S, Martin-Fernandez, M, Owens, R, Nettleship, J, Webb, M, Harrison, M, Lippiat, J, Ponnambalam, S, Peckham, M, Smith, A, Ko Ferrigno, P, Johnson, M, McPherson, M, Tomlinson, D, (2017) Affimer proteins are versatile and renewable affinity reagents. eLIFE 6:e24903. DOI: 10.7554/eLife.24903.

  3. Hughes, D, Tiede, C, Penswick, N, Tang, A, Trinh, C, Mandal, U, Zajac, K, Gaule, T, Howell, G, Edwards, T, Duan, J, Feyfant, E, McPherson, M, Tomlinson, D, Whitehouse, A. (2017) Generation of specific inhibitors of SUMO-1- and SUMO2/3-mediated protein-protein interactions using Affimer (Adhiron) technology. Science Signaling 10, eaaj2005. DOI: 10.1126/scisignal.aaj2005.

  4. Sharma, R., Deacon, S.E., Nowak, D., George, S.E., Szymonik, M.P., Tang, A.A.S., Tomlinson, D.C., Davies, A.G., McPherson, M.J., Wälti, C. (2016) Label-free electrochemical impedance biosensor to detect human interleukin-8 in serum with sub-pg/ml sensitivity. Biosensors and Bioelectronics, 80, 607–613. doi:10.1016/j.bios.2016.02.028