We have a potential PhD studentship available to start in October 2013.
This studentship is part of the MRC Doctoral Training Programme at the University of Bristol. As such you apply to the Programme and the selection process is in competition with all other advertised projects. You can find full details on the programme, including the other available projects here:
This is an exciting inter-disciplinary project bridging ongoing work in Biochemistry and Physics. The project would suit a graduate in biochemistry, cell biology, or biophysics. Full training will be provided and the training elements can be tailored to the interests of the successful candidate.
Please note the eligibility criteria: Only applicants from the UK/EU are eligible for this programme.
Title: Analysis Of Integration Between Membrane And Cytoskeleton Dynamics Using Advanced Light Microscopy
Supervisors: Professor David Stephens (Biochemistry) & Dr Henkjan Gersen (Physics)
To apply for this project please select ‘Faculty of Medical and Veterinary Sciences’ and ‘Biochemistry (PhD)(4-yr)’. Please also identify ‘MRCDTG’ as your fee payer in the Funding section of the online application.
The intricate relationship between endomembranes and cytoskeletal filaments governs the spatial organization, morphology, and function or organelles. Multiple cellular functions that coalesce around Golgi membranes are governed by small GTPases of the Rho family, Cdc42 being the most significant Rho GTPase at the Golgi (1). Recent years have seen the emergence of the septins as a critical component of this system; Cdc42 is known to dictate septin filament organization (2). Septin filaments act in concert with microtubules to direct trafficking around the Golgi (3). Septins also dictate the formation and function of primary cilia, a “cellular antenna” that integrates key signalling pathways essential to normal organism development and tissue function (4, 5, 6). Through selective disruption of Cdc42, Golgi, or septin function, we will define how the classical structure of the Golgi apparatus is defined by septin filaments and vice versa.
Septins adopt a highly conserved structural organization within filaments that can be detected by polarization fluorescence microscopy (7, 8), allowing the subunit architecture of septin filaments to be analysed in an intact cell context. This advanced bioimaging approach will form a core training aspect of the work and would suit a biomedical science graduate with a keen interest in imaging or a biophysics graduate with a strong interest in cell biology. The project bridges the Biochemistry and Physics departments at the University of Bristol. You would be based in the Stephens lab in the School of Biochemistry within newly refurbished cell biology laboratories and the project will involve considerable mammalian cell biology using gene silencing and advanced light microscopy. The Gersen lab, located a short distance away, will provide training in development and application of novel optical microscopy methods, notably fluorescence polarization. Successful PhD training is ensured through links to existing cell biology and nanoscience students in both labs as well as international collaboration.
Informal enquires to David Stephens (firstname.lastname@example.org) or Henkjan Gersen (H.Gersen@bristol.ac.uk) are welcome.
For further details see:
- S. Etienne-Manneville, Cdc42–the centre of polarity. J. Cell Sci. 117, 1291 (Mar 15, 2004).
- G. Joberty et al., Borg proteins control septin organization and are negatively regulated by Cdc42. Nat. Cell Biol. 3, 861 (Oct, 2001).
- E. T. Spiliotis, Regulation of microtubule organization and functions by septin GTPases. Cytoskeleton 67, 339 (Jun, 2010).
- Q. Hu et al., A septin diffusion barrier at the base of the primary cilium maintains ciliary membrane protein distribution. Science 329, 436 (Jul 23, 2010).
- J. R. Bowen, D. Hwang, X. Bai, D. Roy, E. T. Spiliotis, Septin GTPases spatially guide microtubule organization and plus end dynamics in polarizing epithelia. J. Cell Biol. 194, 187 (Jul 25, 2011).
- E. T. Spiliotis, S. J. Hunt, Q. Hu, M. Kinoshita, W. J. Nelson, Epithelial polarity requires septin coupling of vesicle transport to polyglutamylated microtubules. J. Cell Biol. 180, 295 (Jan 28, 2008).
- B. S. DeMay et al., Septin filaments exhibit a dynamic, paired organization that is conserved from yeast to mammals. The Journal of cell biology 193, 1065 (Jun 13, 2011).
- S. A. Rosenberg, M. E. Quinlan, J. N. Forkey, Y. E. Goldman, Rotational Motions of Macromolecules by Single-Molecule Fluorescence Microscopy, . Accounts of Biochemical Research 38, 583 (2005).
Potential applicants are encouraged to contact David when applying.
The deadline for applications is Wednesday 16th January 2013 and interviews are likely to be in the weeks of 11th February and 18th February 2013.