PhD: Applying super-resolution imaging techniques to elucidate the extracellular trafficking of protein aggregates in the brain and their direct role in early neurodegeneration

Vacancy Reference Number
Closing Date
15 Aug 2019
£15009 annual stipend
University of St Andrews, School of Biology
3.5 years
Small aggregates of misfolded proteins are thought to be the main cause for synaptic loss and neuronal death in a variety of neurodegenerative diseases. A large fraction of these aggregates (particularly in the case of amyloid beta) are present in the extracellular space, which despite being almost 20% of the brain volume, is relatively unexplored due to the lack of techniques that can work at the right spatial resolution in physiological conditions. Taking advantage of the techniques we have recently developed with colleagues at the University of Bordeaux and at the University of Cambridge, the PhD project aims to study the way protein aggregates circulate this narrow and convoluted space. The student will use single-molecule fluorescence microscopy techniques and super-resolution imaging to characterise the trafficking of these protein aggregates. Furthermore, the student will investigate which is the direct toxic effect of protein aggregates, in particular studying how amyloid-beta aggregates and alpha-synuclein aggregates interact with their putative receptors. Characterising the trafficking of aggregates and how they interact with receptors at the nanoscale will have deep consequences in the way we understand the spreading of neurodegeneration along the brain. We are looking for an enthusiastic PhD student with a strong background in either physical or biological sciences, willing to work in an interdisciplinary environment studying the brain at the single-molecule level. Experience in biophysics and/or neurosciences will be advantageous. References: Varela J, Rodrigues M, De S, Flagemeier P, Dobson CM, Klenerman D, Lee SF. “Optical structural analysis of individual ?-synuclein oligomers”. Angewandte Chemie International Edition, 4886–4890 (2018). Godin A*, Varela J*, Gao Z*, Danne N, Dupuis J, Lounis B, Groc L, Cognet L. “Single-nanotube tracking reveals the nanoscale organization of the extracellular space in the live brain”. Nature Nanotechnology, 12, 238–243 (2017). Varela J, Dupuis J, Etchepare L, Espana A, Cognet L and Groc L. “Targeting neurotransmitter receptors with nanoparticles in vivo allows single molecule tracking in brain tissue”. Nature Communications, 7:10947 (2016). Varela J*, Ferreira J*, Dupuis JP*, Durand P, Bouchet D, and Groc L. “Single nanoparticle tracking of NMDA receptors in cultured and intact brain tissue”. Neurophotonics, 3:41808 (2016). Xie L, Kang H, Xu Q, Chen MJ, Liao Y, Thiyagarajan M, O’Donnell J, Christensen DJ, Nicholson C, J. Iliff J, Takano T, Deane R, Nedergaard M, “Sleep drives metabolite clearance from the adult brain”. Science 342, 373–7 (2013). Nicholson C, Hrab?tová S, “Brain Extracellular Space: The Final Frontier of Neuroscience”. Biophysical Journal, 113, 2133–2142 (2017).

Further Information

Funding Notes:

This position is fully funded (for 3.5 years) through the ERC Starting Grant “BrainNanoFlow” for UK and European applicants. We regret that we cannot fund candidates from other countries.

Applicants should hold or expect to gain at least a 2:1 Bachelor Degree or equivalent in a related subject area. Due to the interdisciplinary nature of the project, applicants may have background studies in either biological or physical sciences.

Contact Details

Applicants can contact the PI by email ( for informal enquiries prior to submitting the application.