PhD Studentship in Quantitative Pharmacology and Neuroscience: Multilevel modelling of neuronal function: combining metabotropic pathways and membrane excitability in-silico for the quick screening of drugs

University of Reading - School of Pharmacy

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 to 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 multiscale model of electrophysiological response 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 informing the mathematical models. The final aim of this project is to develop and validate a software capable of predicting changes to an artificial neuron based on its exposure to varying concentrations of a given ligand.

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:   

  • Starts 10/2018;
  • 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 online application.
  2. When you are prompted to upload a research proposal, please omit this step.

Application deadline: 30th June 2018.

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.