University of Exeter funding: Sensing and Imaging Synaptic Vesicl

Sensing and Imaging Synaptic Vesicle Trafficking and Neurotransmitter Release - A Novel Opto-Synaptic Interface Ref: 3054

About the award

Supervisors

Prof George Augustine, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore

Prof Frank Vollmer, Living Systems Institute, University of Exeter

About the award:

The University of Exeter (UoE) and Nanyang Technological University (NTU), Singapore are offering six fully funded postgraduate studentships to undertake collaborative research projects at the two institutions, leading to PhD degrees (split-site) to be conferred either by the UoE or NTU.

Students pursuing these postgraduate research projects will benefit from the unique opportunity to conduct their research at both institutions.  Students will be registered at one or other institution, where they will be based for the majority of their time, but will spend at least 12 and not more than 18 months at the partner institution over the duration of the programme.  The frequency and length of stays at each institution will be agreed with successful candidates prior to offers being made.

All six projects are advertised concurrently at both institutions and three will be allocated to each institution after the deadline has passed, based on a collaborative decision made between the UoE and NTU.  The final decision on the successful applicant for each project will be made by the institution hosting the project.  Project allocation will be based on the applicant’s best fit to a project, following a review of applications submitted to each institution.  Applications to undertake the projects at the UoE and NTU are open to all nationalities.
The programme start dates are August 2019 for NTU and September 2019 for UoE

The home institution will determine the regulations that will apply to the successful applicant.  The student’s main supervisor will be based at the home institution.

Project Description:

Whispering Gallery Mode sensors are an advanced optical sensing technology capable of detecting and sizing nanoparticles in the 0.1-500 nm size range. These advanced optical sensing tools have already been utilised for the detection and sizing of Lentiviruses (500 nm) (1), Influenza A virus particles (100 nm) (2), detection of single molecule (1-10 nm) (3) and even single atomic ions (0.1 nm) (4).

This doctoral studentship will enable development of WGM sensors as a novel tool for the detection of neuronal synaptic vesicles (SVs) and the direct detection of synaptic activity at the single-molecule level. SVs are a key organelle in brain function, because they store and release the neurotransmitters that are used for inter-neuronal signalling. Imaging individual SVs at the light-microscope level has been a challenge, due to the very small size (approximately 40 nm in diameter) of SVs. The goal is to determine the stoichiometry and structure of SV aggregates and to characterise the role they play in synaptic vesicle trafficking and the transmission of information between nerve cells. SVs aggregate to form a “reserve pool” of SVs that are mobilised to maintain synaptic transmission during sustained neuronal activity. Thus, being able to sense and visualise these SV clusters in living neurons is important to understand the dynamics of synaptic transmission. It is particularly relevant to clarify the roles of the SV binding proteins called synapsins. It was previously hypothesized that these proteins control the formation of aggregates during mobilization of reserve vesicles in rapidly-firing neurons (6). Elucidating the interplay of synapsin isoforms in SV aggregation and trafficking has important implication for diseases such as epilepsy, schizophrenia and other brain disorders (7).The relative amounts of two synapsin isoforms, synapsins IIA and IB, may constitute a novel signal to control the vesicle replenishment and the dynamics of electro-chemical signalling at the synapse.


NTU
 

In this project, a student will develop novel label-free optical sensing and imaging modalities for nanoscale synaptic processes, combining advanced optical WGM sensors with label-based fluorescence imaging and single-cell electrophysiological modalities. The overall aim of this fellowship is to elucidate the role of synapsin IB and IIA in the regulation of neuronal vesicle dynamics, vesicle aggregation, and vesicle replenishment. Sensing and imaging tools will be developed to visualise the vesicular aggregates, determine the number of vesicles in each aggregate, and determine the protein-vesicle stoichiometry as a function of different synapsin isoforms and their concentrations. The modulation of the dynamics vesicle trafficking by synapsin proteins will be explored on previously inaccessible timescales down to micro-and nanoseconds in vitro reconstituted sensing assays (5). In the second part of the project, the analysis of the dynamical processes in the synapse will be extended to the single molecule level. Leveraging previous progress in techniques for getting neurons to innervate artificial substrates (8), artificial synapses will be formed between nerve cells and optoplasmonic WGM sensors capable of detecting the release of neuronal transmitters down to the single-molecule level. For the first time, an optical interface for the label-free readout of neuronal activity will be established.

The student will have the possibility to combine state-of-the art imaging/ electrophysiology (Augustine) with state-of-the-art nanosensors (Vollmer) to establish an entirely novel platform technology for the analysis of synaptic vesicles, down to the level of single-molecules. This collaborative research will bring about breakthroughs in optical technologies for sensing/neuroscience, which require the joint efforts by the Augustine/Vollmer labs. The doctoral student will have access to state of the art technology that are not available in this combination anywhere else in the world. This will uniquely position the student to acquire skills and training in sensing and imaging which cannot be obtained in any other fellowship or training programme. The fellowship is cutting across disciplines and is ideally supported by the NTU-Exeter partnership aimed at advancing interdisciplinary research and nucleating entirely new fields of studies at the boundaries of physics and biology.

Please contact the supervisors for project-specific queries.

Entry requirements

Successful applicants will need a good first degree (preferably 1st Class Honours and at least an upper Second class honours, or international equivalent) in a relevant field.  Applicants with a Lower Second Class honours degree may be considered if they also have a Master's degree in a relevant field.

Candidates applying to the University of Exeter, for whom English is not their first language will also need to satisfy our English language entry requirements, prior to commencing the programme.

How to apply

Please read all of the information below on how to apply prior to submitting an application for this project.

Note enquiries about NTU's application process should be emailed to gradprog_LKCMedicine@ntu.edu.sg

In order to apply for funding for this studentship, you must click the 'How to Apply' button on this page.

In the application process you will be required to upload several documents as detailed below;
• CV
• Cover Letter
• 2 References
• Transcripts
• IELTS or equivalent (if from a non-english speaking country)

Please note our preferred format is PDF, each file named with your surname and the name of the document, eg. “Smith – CV.pdf”, “Smith – Cover Letter.pdf”, “Smith – Transcript.pdf”

The closing date for applications is 31 January 2019.  Interviews are anticipated to be held February 2019, date to be confirmed.

If you have any general enquiries about the application process please email pgrenquiries@exeter.ac.uk

Please quote reference 3054 on your application and in any correspondence about this studentship.


Reference information
References should be submitted to us directly in the form of a letter. Referees must email their references to us from their institutional email accounts. We cannot accept references from personal/private email accounts, unless it is a scanned document on institutional headed paper and signed by the referee.

It us your responsibility to ensure that your two referees email their references to pgrenquiries@exeter.ac.uk, as we will not make requests for references directly; you must arrange for them to be submitted by 31 January 2019.

All application documents must be submitted in English. Certified translated copies of academic qualifications must also be provided.


Data sharing
During the application process, the University of Exeter may need to make certain disclosures of your personal data to Nanyang Technological University to be able to administer your application, carry out interviews and select candidates.  These are not limited to, but may include disclosures to:

The selection panel and/or management board or equivalent of the relevant programme, which is likely to include staff from NTU.
Administrative staff at NTU related to the relevant programme.
Such disclosures will always be kept to the minimum amount of personal data required for the specific purpose. Your sensitive personal data (relating to disability and race/ethnicity) will not be disclosed without your explicit consent.

Summary

Application deadline:31st January 2019
Value:3 year studentship funding covering tuition fees and an annual maintenance allowance equivalent to research council rates. The maintenance allowance for 2018/19 is £14,777 per annum.
Duration of award:per year
Contact: PGR Enquiries pgrenquiries@exeter.ac.uk