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PhD Studentship in Quantitative Pharmacology and Neuroscience

University of Reading - School of Pharmacy

Qualification Type: PhD
Location: Reading
Funding for: UK Students, EU Students
Funding amount: £14,777
Hours: Full Time
Placed On: 29th November 2018
Closes: 23rd February 2019
Reference: GS18-01
 

Multilevel modelling of neuronal function: combining metabotropic pathways and membrane excitability in-silico.

Supervisors:  

Dr Francesco Tamagnini (Pharmacy), Dr Marcus Tindall (Mathematics & Statistics), Prof Krasimira Tsaneva-Atanasova (University of Exeter, College of Mathematics, Engineering and Physical Sciences).

Project Overview:   

Neurons work as information relays. They integrate information received from the environment at the subcellular scale, generating an appropriate electrophysiological response. The understanding of electrical processes happening at the plasma membrane level has been clarified by Hodgkin and Huxley, combining experimental recordings with mathematical modelling of equivalent electrical circuits. However, quantitative models describing the effects of cell signalling on the cellular response are lacking.

Adenosine is a neurotransmitter binding both A1 (Gi) and A2 (Gs) receptors. A1 and A2 stimulation results in altered neuronal excitability via K+ permeability changes. In this project, we aim to combine a mathematical model of adenosine receptor signal transduction (Tindall) with the Hodgkin-Huxley model of a neuron (Tsaneva-Atanasova), to generate an in-silico unified model, predictive of neuronal function following exposure to chemical stimulation. We will test the predictive capability of the model with whole-neuron patch-clamp recordings (Tamagnini).

The mathematical models formulated during the project will utilise the theory of differential equations (ordinary and partial) solved and analysed both numerically and analytically (e.g. dynamical systems theory, asymptotic methods). The successful candidate will be involved in the design and undertaking of wet laboratory experiments for testing and informing the mathematical models. The candidate will be trained in whole cell patch clamp techniques, with the value added of performing dynamic clamp to test the validity of the model on to a live system. The design and validation of the unified model is aimed at providing a tool (software) for the pre-clinical, ethical, high-throughput screening of newly developed molecules with biological activity and their action on neuronal function.  

Eligibility: 

  • Applicants should hold or expect to gain a minimum of a 2:1 Bachelor Degree or equivalent in Mathematics, Engineering or Neuroscience related subjects. The applicant will have a strong background in mathematics and computer coding (Matlab, Python, C++) and a keenness to engage with and learn wet lab techniques (i.e. pipetting, solution making, single cell electrophysiology).
  • This studentship is open to UK/EU students only.

Funding Details:   

  • Start date, 23rd April 2019
  • 3-year award
  • Tuition fees plus stipend (Research Council UK 2018/19 rate is currently £14,777)

How to apply:  To apply for this studentship please submit an application for a PhD in Pharmacy at http://www.reading.ac.uk/graduateschool/prospectivestudents/gs-how-to-apply.aspx.

*Important notes*

  • 1) Please quote the reference ‘GS18-018’ in the ‘Scholarships applied for’ box which appears within the Funding Section of your on-line application.
  • 2) When you are prompted to upload a research proposal, please omit this step.

Application Deadline: 23rd February 2019

Further Enquiries:  Please note that, where a candidate is successful in being awarded funding, this will be confirmed via a formal studentship award letter; this will be provided separately from any Offer of Admission and will be subject to standard checks for eligibility and other criteria. 

For further details please contact f.tamagnini@reading.ac.uk

   
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