Claire Friel

Contact

• workRoom D116 Medical School
  Queen's Medical Centre
  Nottingham
  NG7 2UH
  UK
• work00 44 115 82 30138
• Claire.Friel@nottingham.ac.uk
• test

Teaching Summary

LIFE2077 (Structure and Function of Proteins), 2nd year, module convenor

LIFE2073 (Macromolecular Systems), 2nd year, module convenor

3rd year BSc and 4th year MSci project students (Biochemistry)

Research Summary

Cytoskeletal Dynamics and the Mechanochemistry of Motor Proteins

The major interest of my lab is the role of the kinesin family of motor proteins in controlling cytoskeletal dynamics. Kinesins are crucial engines of eukaryotic self-organisation. Members of the kinesin super-family interact with the microtubule cytoskeleton and play a vital role in transport of cellular cargo and in cell division.

Microtubules are long slender polymers of the protein tubulin. The microtubule cytoskeleton serves as rails for intracellular transport, plays an essential role in positioning and movement of cellular organelles and forms the mitotic spindle which separates sister chromosomes during cell division. The organisation and dynamics of the microtubule cytoskeleton are controlled by accessory proteins, such as the kinesin super-family. Kinesins are motor proteins that hydrolyse ATP to bring about conformational changes within the characteristic motor domain and thereby alter the strength of the kinesin-microtubule interaction. The majority of kinesins translocate along the microtubule using the nucleotide-dependent cycle of binding and detachment to transport cellular cargo. However, one class of kinesins (kinesin-13) does not translocate, but instead diffuses to the end of the microtubule where it binds and depolymerises the microtubule substrate. Microtubule depolymerases are crucial during mitosis, being involved in generating the force required to separate sister chromatids and also in ensuring the correct segregation of chromosomes by correcting inappropriate kinetochore-microtubule attachments.

Work in my lab is currently focused on the molecular mechanisms of microtubule depolymerising kinesins; using as a model the Mitotic Centromere-Associated Kinesin (MCAK), which plays a crucial role in cell division.

Selected Publications

• BELSHAM, HANNAH R. and FRIEL, CLAIRE T., 2019. Identification of key residues that regulate the interaction of kinesins with microtubule ends CYTOSKELETON. 76(7-8), 440-446
• BELSHAM HR and FRIEL CT, 2017. A Cdk1 phosphomimic mutant of MCAK impairs microtubule end recognition. PeerJ. 5, e4034
• PATEL JT, BELSHAM HR, RATHBONE AJ, WICKSTEAD B, GELL C and FRIEL CT, 2016. The family-specific α4-helix of the kinesin-13, MCAK, is critical to microtubule end recognition. Open biology. 6(10),

• View all publications

• BELSHAM, HANNAH R. and FRIEL, CLAIRE T., 2019. Identification of key residues that regulate the interaction of kinesins with microtubule ends CYTOSKELETON. 76(7-8), 440-446
• QU Y, HAHN I, LEES M, PARKIN J, VOELZMANN A, DOREY K, RATHBONE A, FRIEL CT, ALLAN VJ, OKENVE-RAMOS P, SANCHEZ-SORIANO N and PROKOP A, 2019. Efa6 protects axons and regulates their growth and branching by inhibiting microtubule polymerisation at the cortex. eLife. 8,
• FRIEL CT and WELBURN JP, 2018. Parts list for a microtubule depolymerising kinesin. Biochemical Society transactions. 46(6), 1665-1672
• BELSHAM HR and FRIEL CT, 2017. A Cdk1 phosphomimic mutant of MCAK impairs microtubule end recognition. PeerJ. 5, e4034
• PATEL JT, BELSHAM HR, RATHBONE AJ, WICKSTEAD B, GELL C and FRIEL CT, 2016. The family-specific α4-helix of the kinesin-13, MCAK, is critical to microtubule end recognition. Open biology. 6(10),
• PATEL JT, BELSHAM HR, RATHBONE AJ and FRIEL CT, 2014. Use of stopped-flow fluorescence and labeled nucleotides to analyze the ATP turnover cycle of kinesins. Journal of visualized experiments : JoVE.
• SANHAJI M, RITTER A, BELSHAM HR, FRIEL CT, ROTH S, LOUWEN F and YUAN J, 2014. Polo-like kinase 1 regulates the stability of the mitotic centromere-associated kinesin in mitosis. Oncotarget. 5(10), 3130-44
• MOURAD SANHAJI, CLAIRE T FRIEL, LINDA WORDEMAN, FRANK LOUWEN and JUPING YUAN, 2012. Mitotic centromere-associated kinesin (MCAK): a potential cancer drug target. Oncotarget. 2, 935-947
• FRIEL, CLAIRE T. and HOWARD, JONATHON, 2012. Coupling of kinesin ATP turnover to translocation and microtubule regulation: one engine, many machines Journal of Muscle Research and Cell Motility.
• FRIEL, CLAIRE T, BAGSHAW, CLIVE R and HOWARD, JONATHON, 2011. Analysing the ATP turnover cycle of microtubule motors. Methods in Molecular Biology. 777, 177-92
• GELL, CHRISTOPHER, FRIEL, CLAIRE T, BORGONOVO, BARBARA, DRECHSEL, DAVID N, HYMAN, ANTHONY A and HOWARD, JONATHON, 2011. Purification of tubulin from porcine brain. Methods in Molecular Biology. 777, 15-28
• FRIEL, C.T. and HOWARD, J., 2011. The kinesin-13 MCAK has an unconventional ATPase cycle adapted for microtubule depolymerization EMBO Journal. 30(19), 3928-3939
• CHEN, M.M., BARTLETT, A.I., NERENBERG, P.S., FRIEL, C.T., HACKENBERGER, C.P.R., STULTZ, C.M., RADFORD, S.E. and IMPERIALI, B., 2010. Perturbing the folding energy landscape of the bacterial immunity protein Im7 by site-specific N-linked glycosylation Proceedings of the National Academy of Sciences of the United States of America. 107(52), 22528-22533
• GELL, CHRISTOPHER, BORMUTH, VOLKER, BROUHARD, GARY J, COHEN, DANIEL N, DIEZ, STEFAN, FRIEL, CLAIRE T, HELENIUS, JONNE, NITZSCHE, BERT, PETZOLD, HEIKE, RIBBE, JAN, SCHÄFFER, ERIK and STEAR, JEFFREY H, 2010. Microtubule dynamics reconstituted in vitro and imaged by single-molecule fluorescence microscopy. Methods in Cell Biology. 95, 221-45
• SANHAJI, M., FRIEL, C.T., KREIS, N.-N., KRÄMER, A., MARTIN, C., HOWARD, J., STREBHARDT, K. and YUAN, J.P., 2010. Functional and spatial regulation of mitotic centromere-associated kinesin by cyclin-dependent kinase 1 Molecular and Cellular Biology. 30(11), 2594-2607
• FRIEL, C.T., SMITH, D.A., VENDRUSCOLO, M., GSPONER, J. and RADFORD, S.E., 2009. The mechanism of folding of Im7 reveals competition between functional and kinetic evolutionary constraints Nature Structural & Molecular Biology. 16(3), 318-324
• MORTON, VICTORIA L, FRIEL, CLAIRE T, ALLEN, LUCY R, PACI, EMANUELE and RADFORD, SHEENA E, 2007. The effect of increasing the stability of non-native interactions on the folding landscape of the bacterial immunity protein Im9. Journal of Molecular Biology. 371(2), 554-68
• MASCA, S.I, RODRIGUEZ-MENDIETA, I.R, FRIEL, C.T, RADFORD, S.E and SMITH, D.A., 2006. A Detailed Evaluation of the Performance of Microfluidic T-Mixers using Fluorescence and Ultra-violet Resonance Raman Spectroscopy. Review of Scientific Instruments. 77, 055105
• HACKENBERGER, C.P.R, FRIEL, C.T and RADFORD, S.E. AND IMPERIALI, B., 2005. Semi-synthesis of a Glycosylated Im7 Analogue for Protein Folding Studies. Journal of the American Chemical Society. 127, 12882-12889
• CRANZ-MILEVA, S, FRIEL, CT and RADFORD, SE, 2005. Helix Stability And Hydrophobicity In The Folding Mechanism Of The Bacterial Immunity Protein Im9 Protein Engineering Design & Selection. 18(1), 41-50
• MAXWELL, KL, WILDES, D, ZARRINE-AFSAR, A, DE LOS RIOS, MA, BROWN, AG, FRIEL, CT, HEDBERG, L, HORNG, JC, BONA, D, MILLER, EJ, VALLEE-BELISLE, A, MAIN, ERG, BEMPORAD, F, QIU, LL, TEILUM, K, VU, ND, EDWARDS, AM, RUCZINSKI, I, POULSEN, FM, KRAGELUND, BB, MICHNICK, SW, CHITI, F, BAI, YW, HAGEN, SJ, SERRANO, L, OLIVEBERG, M, RALEIGH, DP, WITTUNG-STAFSHEDE, P, RADFORD, SE, JACKSON, SE, SOSNICK, TR, MARQUSEE, S, DAVIDSON, AR and PLAXCO, KW, 2005. Protein Folding: Defining A "Standard" Set Of Experimental Conditions And A Preliminary Kinetic Data Set Of Two-State Proteins Protein Science. 14(3), 602-616
• PACI, E, FRIEL, C.T, LINDORFF-LARSEN, K, RADFORD, S.E and KARPLUS, M. & VENDRUSCOLO, M., 2004. Comparison of the transition state ensembles for folding of Im7 and Im9 determined using all-atom molecular dynamics simulations with Φ-value restraints. Proteins: Structure, Function and Genetics. 54, 513-525
• FRIEL, CT, BEDDARD, GS and RADFORD, SE, 2004. Switching Two-State To Three-State Kinetics In The Helical Protein Im9 Via The Optimisation Of Stabilising Non-Native Interactions By Design Journal Of Molecular Biology. 342(1), 261-273
• FRIEL, CT, CAPALDI, AP and RADFORD, SE, 2003. Structural Analysis Of The Rate-Limiting Transition States In The Folding Of Lm7 And Lm9: Similarities And Differences In The Folding Of Homologous Proteins Journal Of Molecular Biology. 326(1), 293-305