... understanding life in molecular detail

Dr Joe Cockburn

Structural biology of the cytoskeleton

The cytoskeleton is a dynamic scaffold inside cells that determines cell shape, allows cells to move, and functions as a set of internal tracks for transport of cellular components (e.g. organelles) by molecular motors. Defects or deregulation of cytoskeletal processes are implicated in various pathogenic states such as viral infections, neurodegeneration, developmental defects and cancer.

The research of our group aims to understand how the positioning of cellular components is encoded at the molecular level. We combine structural biology (principally X-ray crystallography and increasingly cryo-EM) with biophysical and cell biology approaches to obtain a unified understanding of the biological processes under study.

Are you interested in doing a PhD in structural cell biology? We are currently accepting applications for two PhD projects for 2019 entry:

- The structure and function of retinal photoreceptor connecting cilium proteins. Defects in these proteins are associated with inherited disorders characterized by blindness and/or kidney failure. In this project you will investigate the structure and function of these proteins by X-ray crystallography, cryo-EM and cell biology approaches. (BBSRC White Rose DTP project supervised jointly between the Cockburn, Johnson and Ranson labs at the University of Leeds; please see https://www.findaphd.com/phds/project/structural-and-functional-studies-on-proteins-required-for-vision/?p59606 for more details. Closing date: 7th January 2019.)

-  The molecular pathogenesis of KIF5A mutations.  The microtubule motor KIF5A is involved in long-range axonal transport. KIF5A mutations cause inherited spastic paraplegias. This project will investigate the effects of pathogenic mutations on the structure and function of KIF5A. (MRC DiMeN DTP project supervised jointly between the Twelvetrees and De Vos labs at the University of Sheffield and the Cockburn lab at the Univerisity of Leeds; please see https://www.findaphd.com/phds/project/mrc-dimen-doctoral-training-partnership-how-do-neurodegenerative-mutations-in-kinesin-1-alter-its-structure-motility-and-cellular-function/?p103997 for more details. Closing date: 21st January 2019.)




Current major projects include:
  • How cellular cargo molecules recruit and regulate cytoskeletal molecular motors
  • Towards a molecular-level understanding of the ciliary transition zone


The main areas of current activity within my lab are described in more detail in the sections below.

How cellular cargo molecules recruit and regulate cytoskeletal molecular motors

The cytoplasm is a highly crowded environment containing tens of thousands of different protein species, mRNA molecules, ribosomes, vesicles and organelles. Cellular function is critically dependent on the correct localisation of these components in space and time.

The movement of cellular cargoes over long distances requires dedicated motor proteins (kinesins and cytoplasmic dynein) that use ATP hydrolysis to power movement along a dynamic network of tracks called microtubules. How these motors couple ATP hydrolysis to movement is now fairly well understood, and attention in the field is now turning towards the questions of how cellular cargoes recruit molecular motors and regulate their motility. The combined action of all the kinesin and dynein motors inside your body is very powerful – if all the kinesin motors in your cells were working at full tilt all the time, they would use up somewhere in the region of 8000 kcal of energy per day! Molecular motors must therefore be carefully regulated by their cargoes to ensure that they only consume energy then they are needed.

The main focus of our activity at present is on kinesin-1, which mediates the long-range transport of diverse cellular cargoes (proteins, mRNPs, vesicles, organelles and viruses). We use structural biology, biophysical and cell biology techniques to understand how kinesin-1 switches itself off when not in use, how cargo molecules bind to kinesin, and how this “switches on” kinesin-1.

Towards a molecular-level understanding of the ciliary transition zone (in collaboration with Prof. Colin Johnson at the Faculty of Medicine and Health, University of Leeds)

Cilia are the antennae of eukaryotic cells, sensing a wide variety of environmental signals (e.g light, molecules, proteins, and fluid flow). The cilium possesses a distinct protein and lipid composition relative to the rest of the cell. This is maintained by the transition zone, a large complex of over 20 proteins at the base of the cilium that controls the exchange of material between the cilium and the rest of the cell. Mutations in transition zone genes result in a range of autosomal recessive inherited disorders, such as nephronophthisis, Joubert Syndrome and Meckel-Gruber syndrome. Around 1% of the population are genetic carriers for these conditions.

We use a combination of structural and cell biology approaches to obtain a unified, molecular-level understanding of the function of transition zone proteins, and how mutations in transition zone genes cause diseases. This will aid in the development of gene therapies against these conditions.


Detailed research programme                  Close ▲

Lecturer in X-ray Crystallography

DPhil (University of Oxford) 2000-2005
Postdoctoral Fellow (Pasteur Institute, Paris) 2005-2011
Postdoctoral Fellow (London Research Institute, CRUK) 2011-2014

Astbury building
School of Molecular and Cellular Biology


Selected Publications

  1. Cockburn JJB, Hesketh SJ, Mulhair P, Thomsen M, O’Connell MJ, Way M. Insights into kinesin-1 activation from the crystal structure of KLC2 bound to JIP3. Structure 2018 Nov 6;26:1-13. https://doi.org/10.1016/j.str.2018.07.011).

  2. Bravo JPK, Borodavka A, Barth A, Calabrese AN, Mojzes P, Cockburn JJB, Lamb DC, Tuma R. Stability of local secondary structure determines selectivity of viral RNA chaperones. Nucleic Acids Res. 2018 Sep 6;46(15):7924-7937. doi: 10.1093/nar/gky394

  3. S Shakeel, EC Dykeman, SJ White, A Ora, JJB Cockburn, SJ Butcher, PG Stockley, R Twarock. Genomic RNA folding mediates assembly of human parechovirus. Nature Commun. 2017 Feb 23;8(1):5. doi: 10.1038/s41467-016-0011-z.

  4. Hesketh EL, Meshcheriakova Y, Dent KC, Saxena P, Thompson RF, Cockburn JJ, Lomonossoff GP, Ranson NA. Mechanisms of assembly and genome packaging in an RNA virus revealed by high-resolution cryo-EM. Nat Commun. 2015 Dec 10;6:10113. doi: 10.1038/ncomms10113.