PhD Study : A Computational Model of Regulating Neuronal Excitability by GABA Neurons

Summary

Background: It is now known that astrocytes, the major class of glial cells, detect neuronal release of excitatory neurotransmitters and respond by releasing gliotransmitters thus modulating neuronal performance. However, very little is known about how GABA uptake by astrocytes modulates activity in neuronal networks. Specifically, recent findings [4, 5] have shown that the GAT3 transporter facilitates the uptake of extracellular GABA and this is accompanied by a large increase in intracellular Na+ concentration, which can reverse the Na+/Ca2+ exchanger causing an intercellular increase in Ca2+. This may have an important role in regulating blood flow and also can result in the release of gliotransmitters, which is believed to modulate synaptic strength and transmission. Moreover, it is now believed that GAT3 induces a rise in extracellular adenosine that acts at presynaptic adenosine receptors and this is likely to cause a decrease in secondary messengers within cells. This is a completely novel mechanism of glia-neuron communication and capturing this interaction will be the major focus of this PhD.

Project Aim: This project has the aim of developing a computational model of how the transporter GAT3 mediated signalling between astrocytes and neurons. This work will build on recent research within the CNET research team based at the Intelligent Systems Research Centre (ISRC), Ulster University. The CNET team have a long history of modelling the role of glial in brain function [3-5] and are now seeking a highly motivated graduate student to work with them in modelling the underlying mechanism/s for GABA uptake by astrocytes, which constitutes another form of neuron-glia signalling.

Outcome: This project will develop a computational model of the transporter GAT3 and how this transporter mediated signalling between astrocytes and neurons. Success in this project will have a major impact on existing computational models. Additionally, at the end of the PhD study period the candidate will have gained significant expertise in computational modelling and neuroscience Resources: This successful candidate will be supported by CNET team comprising academic staff and existing RA’s/PhD students with expertise in modelling astrocyte – neuron interactions. Also available to the candidate are state-of-the-art facilities which includes MATLAB/C/C++/Python and cluster computing.

References

[1] Doengi M, Hirnet D, Coulon P, Pape H-C, Deitmer JW and Lohr C, “GABA uptake-dependent Ca2+ signaling in developing olfactory bulb astrocytes”, Proc. Natl. Acad. Sci. U. S. A. 106, 17570–5 (2009).

[2] Boddum, K. et al. Nat. Commun. (in press).

[3] Wade JJ, McDaid LJ, Harkin J, Crunelli V, Kelso JAS (2012), Self-repair in a bidirectionally coupled astrocyte-neuron (AN) system based on retrograde signalling, Front. Comput. Neurosci., 26 September 2012 | doi: 10.3389/fncom.2012.00076.

[4] Wade JJ, McDaid LJ, Harkin J, Crunelli V, Kelso JAS (2011), Bidirectional Coupling between Astrocytes and Neurons Mediates Learning and Dynamic Coordination in the Brain: A Multiple Modeling Approach. PLoS ONE 6(12): e29445. doi:10.1371/journal.pone.0029445.

[5] Naeem M, McDaid L, Harkin J, Wade J, Marsland J, “On The Role of Astroglial Syncytia in Self-Repairing Spiking Neural Networks”, IEEE Trans. Neural Net. & Learning Sys, 2015.

Essential criteria

Applicants should hold, or expect to obtain, a First or Upper Second Class Honours Degree in a subject relevant to the proposed area of study.

We may also consider applications from those who hold equivalent qualifications, for example, a Lower Second Class Honours Degree plus a Master’s Degree with Distinction.

In exceptional circumstances, the University may consider a portfolio of evidence from applicants who have appropriate professional experience which is equivalent to the learning outcomes of an Honours degree in lieu of academic qualifications.

• Experience using research methods or other approaches relevant to the subject domain

Desirable Criteria

If the University receives a large number of applicants for the project, the following desirable criteria may be applied to shortlist applicants for interview.

• First Class Honours (1st) Degree
• Masters at 70%
• For VCRS Awards, Masters at 75%
• Publications - peer-reviewed

Funding and eligibility

The University offers the following levels of support:

Vice Chancellors Research Studentship (VCRS)

The following scholarship options are available to applicants worldwide:

• Full Award: (full-time tuition fees + £19,000 (tbc))
• Part Award: (full-time tuition fees + £9,500)
• Fees Only Award: (full-time tuition fees)

These scholarships will cover full-time PhD tuition fees for three years (subject to satisfactory academic performance) and will provide a £900 per annum research training support grant (RTSG) to help support the PhD researcher.

Applicants who already hold a doctoral degree or who have been registered on a programme of research leading to the award of a doctoral degree on a full-time basis for more than one year (or part-time equivalent) are NOT eligible to apply for an award.

Please note: you will automatically be entered into the competition for the Full Award, unless you state otherwise in your application.

Department for the Economy (DFE)

The scholarship will cover tuition fees at the Home rate and a maintenance allowance of £19,000 (tbc) per annum for three years (subject to satisfactory academic performance).

This scholarship also comes with £900 per annum for three years as a research training support grant (RTSG) allocation to help support the PhD researcher.

• Candidates with pre-settled or settled status under the EU Settlement Scheme, who also satisfy a three year residency requirement in the UK prior to the start of the course for which a Studentship is held MAY receive a Studentship covering fees and maintenance.
• Republic of Ireland (ROI) nationals who satisfy three years’ residency in the UK prior to the start of the course MAY receive a Studentship covering fees and maintenance (ROI nationals don’t need to have pre-settled or settled status under the EU Settlement Scheme to qualify).
• Other non-ROI EU applicants are ‘International’ are not eligible for this source of funding.
• Applicants who already hold a doctoral degree or who have been registered on a programme of research leading to the award of a doctoral degree on a full-time basis for more than one year (or part-time equivalent) are NOT eligible to apply for an award.

Due consideration should be given to financing your studies. Further information on cost of living