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Personal profile

Overview

Most cells have an internal transport system that uses filamentous protein polymers (microtubules) as railway tracks for the movement of a whole range of different structures. These cargoes are transported by tiny motors attached to their surface, which then walk along the track. The distances travelled in most cells is small, but in nerve cells it can be a metre or more. The tracks themselves are polar, in that one end is different to the other. Unlike a car where you change gear to switch direction, the cellular cargoes have to switch the motor protein. We can see these cellular structures moving using light microscopy both in living cells, and in extracts we make from cells. We are interested in which motors move each cargo, and how they are regulated in time and space. We would also like to know how the movement of cargoes constributes to their cellular function. These molecular motors are crucial for normal cell function, and even slight decreases in their activity can lead to serious consequences for nerve cells in particular, and may contribute to motor neuron diseases and Alzheimer's disease.

Biography

I obtained a B.Sc. in Biochemistry and a D. Phil. in Cell Biology from the University of York. I then went to the European Molecular Biology Laboratory in Heidelberg, Germany, to take up a 3 year Post-Doc position with the late Thomas Kreis. I then travelled to the USA to join Ron Vale's laboratory at the University of California, San Francisco, for 2.5 years. I returned to the UK as an independent Staff Scientist in the Structural Studies division of the MRC Laboratory of Molecular Biology in Cambridge. From there I moved to the University of Manchester in 1994 as a Lister Institute Senior Research Fellow to start my own laboratory. I then took up a lectureship position, followed by a Senior Lectureship and professorship.

Research interests

Microtubule motors in health and disease

Our research centres on microtubule motor proteins: their regulation, diversity and function, both in healthy cells and how their misfunction may contribute to disease.

Microtubules and their associated motor proteins play a variety of vital roles in orchestrating many processes within higher eukaryotes, such as membrane traffic and cell division. A major challenge is to understand how the cell co-ordinates and regulates all aspects of microtubule-based movement, both temporally and spatially. A number of diseases have been linked malfunction of motor proteins, particularly within the nervous system, and it is certain that more examples will be identified. In addition, our research has shown that the motor protein cytoplasmic dynein is an early target for destruction during programmed cell death, and that disrupting cytoplasmic dynein function in otherwise normal cells can itself trigger apoptosis. Taken together with the essential function of motors in cell division and in transporting tumour suppressors such as Adenomatous Polyposis Coli, this raises the possibility that abnormal motor function could play a part in the development of cancer.

The reconstitution of microtubule-based movement in cell-free systems provides a powerful approach for analysing the components involved. We use cell-free extracts as a rich source of motors, microtubules and membranes. High resolution video-enhanced light microscopy is then used to follow the movement of organelles along microtubules in real time. We also track the movement of green fluorescent protein-tagged cargoes within living cells using timelapse fluorescence microscopy. We combine these motility assays with a wide range of cell and molecular biological techniques to ask the following interconnected questions:

  • how are membrane-associated motors regulated during the cell cycle?
  • how are membrane movement and membrane traffic integrated within space and time?
  • how does one motor bind to many different cargoes?

We have recently made progress on the third topic, as we have shown that different isoforms of kinesin light chain are important in targeting kinesin-1 to distinct membranes (Wozniak & Allan, 2006)(Open access manuscript version : PDF 10.2Mb)

Teaching

I am committed to engaging students with the field of cell biology. I give 11 lectures to 1st year students on the Molecules to Cells course. I set up the second year Cell Biology Research Skills Module practical course. Lisa Swanton and I deliver two weeks of this practical in which students have the chance to learn how to use research-quality fluorescence microscopes to investigate protein localisation within the cell. This practical gives the students the opportunity to design, carry out and interpret their own experiments in order to determine the localisation of an unknown green fluorescent protein chimera that they are given.

Expertise related to UN Sustainable Development Goals

In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):

  • SDG 3 - Good Health and Well-being

Areas of expertise

  • QH301 Biology
  • Cell Biology

Research Beacons, Institutes and Platforms

  • Dementia@Manchester

Keywords

  • Cell biology
  • Cytoskeleton
  • Motor proteins
  • Membrane traffic
  • Endosome

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