... understanding life in molecular detail

Dr Takashi Ochi

Centrosome, Cilia, Structural protein, Structure biology

Our lab is interested in determining the structures of the centrosome and basal body primary using cryo-electron microscopy and X-ray crystallography. The centrosome is a major microtubule-organising centre, and its core structure centriole is essential for generating a cilium, where the centriole is called the basal body.

Current major projects include:
  • The core structure of the centriole/basal body
  • Molecular mechanisms of generating basal-body structures
  • Evolution of XRCC4/SAS6 superfamily in centrosomes and NHEJ

The centrosome is a major microtubule-organising centre (MTOC) and probably the largest protein assembly (~200 nm diameter and ~400 nm length) found in aminal cells. The centrosome is comparised of a pair of centrioles surrounded by pericentriolar matral (PCM) and centriolar satellites. The centriole has a characteristic 9-fold rotational symmetry, which is created by nine copies of parallely aligned-microtubule blades. One of the centriole pair has appendage structures that are crucial for generating a cilium. Cilia have further extended-microtubule blades (axoneme) from centrioles, which are called basal bodies at cilia. Centrioles and basal bodies are essential the same structure, but their accessary structures are slightly different. Cilia can be largely classified into motile and non-motile. Motile cilia, which can be found more than one per cell, generate fluid flow in our airway, reproduction system & brain and are essential for locomotion of sperm cells. Many unicellular organisms such as green algae also use cilia to swim in fresh water. Non-motile cilia (primary cilia) are present one per cell and mediate intra-cellular signal transductions (e.g. hedgehog signalling). Inherited mutantions in genes related to these organells result in human diseases ciliopathies. Ideally, we want to explain exact mechanisms why mutations in centrosomal / ciliary genes cause diseases. However, this is challenging because a large number of proteins involve in centrosomal and ciliary functions (e.g. proteomics studies identified >100 proteins associate with centrosomes), and we do not know exact functions of many of the proteins. Thus, studying molecular mechanisms of centrosomal and ciliary functions will contribute to understand disease-causing mechanisms as well as to gain knowledge of basic biology.

Our group focuses on determining the atomic stuctures of centrosomes and basal bodies. In order to achieve this, we take both top-down and bottom-up approaches. For the top-down approach, we use cryo-electron tomography (cryo-ET) to observe and characterise the whole centrosomes and basal bodies. For the bottom-up approach, we focus on single protein or sub-complexes of centrosomal / basal-body proteins to determine their structures using X-ray crystallography & cryo-EM and their functrions using biochemical/biophysical studies. Proteins that we are currently interested in are the ones belong to the XRCC4/SAS6 superfamily.

This superfamily is comprised of four protein families SAS6, XRCC4, XLF and PAXX, which all share similar protein folds. SAS6 is a centriolar protein and is the core of a sub-structure of the centriole called the cartwheel, which is key to generate the 9-fold rotational symmetry of the centriole. Remarkably, SAS6 itself assembles into a ring structure having a 9-fold rotational symmetry to scaffold other centrosomal proteins. On the other hand, XRCC4, XLF and PAXX play roles in non-homologous end joining (NHEJ) DNA repair for DNA double-strand breaks. XRCC4 and XLF scaffold two broken DNA ends by forming helical filaments using a similar interface that SAS6 uses to make its ring structure. Therefore, these proteins interestingly use a similar oligomersation mechanism to play a role as scaffold in two different biological systems.

Detailed research programme                  Close ▲

University Academic Fellow

PhD (University of Cambridge)
Postdoc (University of Cambridge) 2011-2016
Postdoc (MRC LMB, Cambridge) 2016-2018
UAF (Leeds) 2018-present

Astbury 8.107
School of Molecular and Cellular Biology
0113 3432528


Selected Publications

  1. Wang, J. L., Duboc, C., Wu, Q., Ochi, T., Liang, S., Tsutakawa, S. E., Lees-Miller, S. P., Nadal, M. Tainer, J. A., Blundell, T. L., and Strick, T. R. (2018). Dissection of DNA double-strand-break repair using novel single-molecule forceps. Nature Structural & Molecular Biology 25, 482-487.

  2. Wu, Q., Paul, A., Mehmood, S., Su, D., Ochi, T., Robinson, C. V., Wang, B. and Blundell, T. L. (2016). Phosphorylated Abraxas promotes dimerization and accumulation of BRCA1 at DNA damage sites. Mol. Cell 61, 1-15

  3. Ochi, T., Blackford, A. N., Coates, J., Jhujh, S., Mehmood, S., Tamura, N., Travers, J., Wu, Q., Draviam, V. M., Robinson, C. V., Blundell T. L. and Jackson S. P. (2015). PAXX, a paralog of XRCC4 and XLF, interacts with Ku to promote DNA double-strand break repair. Science 347, 185-188

  4. Ochi, T., Gu, X. and Blundell, T. L. (2013). Structure of the catalytic region of DNA ligase IV in complex with an Artemis fragment sheds light on Double-Strand Break Repair. Structure 21, 1-8