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How do organelles use short tracks to make long trips in cells


School of Life Sciences

About the Project

The cells of our body contain internal structures (organelles) that perform essential functions e.g. energy production. Organelle transport is vital for function and the viability of cells and the whole body. In line with this transport defects result in disease e.g. Cystic Fibrosis, hypercholesterolemia, neuro-degeneration and some cancers.

To allow transport, cells have evolved a protein-based machinery known as the cytoskeleton that moves organelles. The cytoskeleton comprises subcellular protein filaments or ’tracks’ and motor proteins that attach to cargo and convert chemical energy, from food, into movement. Thus moving cargo along the tracks. There are two-types of tracks in our cells; microtubules (MTs) and actin filaments (AFs).

Most researchers consider that MTs and AFs co-operate to regulate fast long distance, and slow local transport in cells. This makes intuitive sense as MTs often form a polarised radial network of long filaments that span from the centre to the periphery of the cell and appear ideal routes for long-range transport. The AF cytoskeleton meanwhile is more complex, comprising a mixed network of often short branched and linear filaments, and appears to lack uniform polarity.

However, using melanin-containing pigment granules (melanosomes) of skin pigment cells (melanocytes), we recently discovered that short linear AFs, built by SPIRE and FMN proteins at the melanosome surface, and the melanosome associated motor myosin-Va (MyoVa) can rapidly disperse melanosomes over long distances. Thus the overall aim of this proposal is to understand how short-range MyoVa/AF mechanisms drive long-range transport in cells.

We are a small research group located in the Medical School (QMC campus) working in highly interactive environment alongside other teams investigating related research. In addition to regular group meetings we are part of a cytoskeleton and cell division group of several research teams at Nottingham that meets regularly to discuss our latest research in a friendly and informal environment.

Our research is multidisciplinary in nature using a range of molecular and cell biological methods e.g. cloning, PCR, confocal and super-resolution microscopy. You will also have the opportunity to benefit from training provided by our collaborators in electron microscopy and in silico modelling of cell biological process.

Finally as a PhD student in the group you will be encouraged to attend national and international meetings at which you can present the findings of your research to leaders in this research area.

The University of Nottingham is one of the world’s most respected research-intensive universities, ranked 8th in the UK for research power (REF 2014). Students studying in the School of Life Sciences will have the opportunity to thrive in a vibrant, multidisciplinary environment, with expert supervision from leaders in their field, state-of-the-art facilities and strong links with industry. Students are closely monitored in terms of their personal and professional progression throughout their study period and are assigned academic mentors in addition to their supervisory team. The School provides structured training as a fundamental part of postgraduate personal development and our training programme enables students to develop skills across the four domains of the Vitae Researcher Development Framework (RDF). During their studies, students will also have the opportunity to attend and present at conferences around the world. The School puts strong emphasis on the promotion of postgraduate research with a 2-day annual PhD research symposium attended by all students, plus academic staff and invited speakers.

Funding Notes

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. International applicants should visit our International Research Scholarships page for information regarding fees and funding at the University View Website.

References

Alzahofi N., Robinson C.L., Welz T., Page E.L., Briggs D.A., Stainthorp A.K., Reekes J., Elbe D.A., Straub F., Tate E.W., Goff P.S., Sviderskaya E.V., Cantero M., Montoliu L., Bailly M., Kerkhoff E., Hume A.N. Rab27a co-ordinates actin-dependent transport by controlling organelle-associated motors and track assembly proteins. bioRxiv, doi: https://doi.org/10.1101/314153.

Evans RD, Robinson C, Briggs DA, Tooth DJ, Ramalho JS, Cantero M, Montoliu L, Patel S, Sviderskaya EV, Hume AN. Myosin-Va and dynamic actin oppose microtubules to drive long-range organelle transport. Curr Biol. 2014 Aug 4;24(15):1743-50. https://pubmed.ncbi.nlm.nih.gov/25065759/

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