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)
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.
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