Unravelling how cells use local transport mechanisms to move cargo long-distance.
Understanding the molecular mechanisms regulating organelles transport in cells is fundamental for improving health and the development of future medicine. The importance of this area of research was recently underlined by the award of the 2013 Nobel Prize in Physiology/Medicine to Randy Schekman, James Rothman and Thomas Sudhof ‘for their discoveries of machinery regulating vesicle traffic, a major transport system in our cells’. However, in spite of much progress many important aspects of the organisation of intracellular transport remain poorly understood. This PhD project aims to investigate one such area – namely how networks of dynamic actin filaments (F-actin) and myosin motors drive organelle transport in animal cells.
According to the cell biology textbook microtubules and F-actin regulate transport in animal cells in a manner akin to the transport infrastructure of a developed nation. This ‘highways and local roads’ model suggests that microtubules are tracks for long-distance transport (highways) between the cell centre and periphery, while actin filaments (local roads) and myosin motors pick up cargo at the cell periphery and transport it for the ‘last micron’ to its final destination. This model makes intuitive sense as microtubules typically form a polarised network of tracks, spanning 10s of microns from the centrosome to the cell periphery, which appears ideal for long-range transport. Meanwhile, actin filament architecture is much more complex and an obvious track network is often not visible.
However, recent ground-breaking work from our group, co-first authored by a current PhD student, has revealed that the actin motor, myosin-Va, and a population of dynamic F-actin can drive long-range organelle transport from the cell centre to the periphery in opposition to microtubules in skin pigment cells (melanocytes) (Evans et al, Current Biology 2014;24(15):1743-50.). Interestingly, similar results have been reported by other leading groups of cell biologists studying organelle transport in other cell systems (Ooctyes: Schuh, Nat Cell Biol. 2011;13(12):1431-6; Pancreas: Geron et al, Proc Natl Acad Sci U S A. 2013;110(26):10652-7). This suggests that such actin/myosin-based mechanisms of long-range transport may be widespread in animal cells.
This project follows on from this work (see above) and aims characterise the molecular mechanism by which dynamic actin works in concert with myosin-Va to drive long-range organelle transport. This represents an exciting opportunity to train with a leading research group in a dynamic and multi-disciplinary environment and participate in a new area of research at the cutting-edge of cell biology.
The results of this research will be presented at meetings such as the ‘Actin dynamics meeting’ in Regensberg, Germany, and the Gordon Research Conference on ‘Muscle and Molecular Motors’ in Vermont, USA, and will be published in peer-reviewed journals.
Throughout the project you will receive training in molecular biology, cell culture, flow cytometry, protein purification as well as state-of-the-art imaging techniques such as confocal, total internal reflectance fluorescence (TIRF) and super-resolution structured illumination (SIM) microscopy. Through participation in weekly research group meeting, post-graduate seminars and UK and international meetings you will develop your presentation skills and be exposed to wide range of related research.
Home applicants should contact the supervisor to determine the current funding status for this project. EU applicants should visit the Graduate School webpages for information on specific EU scholarships http://www.nottingham.ac.uk/graduateschool/funding/index.aspx . International applicants should visit our International Research Scholarships page for information regarding fees and funding at the University http://www.nottingham.ac.uk/studywithus/international-applicants/scholarships-fees-and-finance/scholarships/research-scholarships.aspx
Evans et al, Current Biology 2014;24(15):1743-50.
Hammer JA 3rd, Sellers JR. Nat Rev Mol Cell Biol. 2011 Dec 7;13(1):13-26.
Hume AN, Seabra MC. Biochem Soc Trans. 2011 Oct;39(5):1191-6.
How good is research at University of Nottingham in Biological Sciences?
FTE Category A staff submitted: 90.86
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