Dr Joe Cockburn

Profile

After graduating in Natural Sciences from Cambridge, I obtained by DPhil from the Division of Structural Biology, University of Oxford, and performed postdoctoral research at the Pasteur Institute, Paris. During this time, my research focused on the structural biology of viruses, solving the first high-resolution structure of an enveloped virus (bacteriophage PRD1) and solving several structures of complexes of dengue virus envelope proteins bound to antibodies.

My interest in virus:host interactions continued with a postdoc at the London Research Institute to investigate kinesin-1 recruitment by vaccinia virus, which is where my interests in the microtubule cytoskeleton began. I have been a lecturer and group leader at the University of Leeds since 2014.

Research interests

Our interests lie in combining structural biology (principally X-ray crystallography), biophysical and cell biology approaches to obtain a unified understanding of cellular function. Broadly speaking, the research of my group aims to understands how cellular components are positioned inside the cell through interactions with the cytoskeleton.

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

How cellular cargo molecules recruit molecular motors and regulate their activities

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. 

Qualifications

• DPhil, University of Oxford (2005)
• BA, MSci, Fitzwilliam College, University of Cambridge (2000)

Current postgraduate researchers

• Travis Bannell

Projects

<li><a href="//phd.leeds.ac.uk/project/1927-using-cryo-electron-microscopy-to-study-large-protein-complexes-that-mediate-the-female-post-mating-response">Using cryo-electron microscopy to study large protein complexes that mediate the female post-mating response</a></li>