This project is one of a number which are funded by the Engineering and Physical Sciences Research Council (EPSRC) Doctoral Training Partnership to commence in September, 2016. The studentships will provide funding for a stipend (currently £14,057 per annum
for 2015/16), research costs of £3,000 and UK/EU tuition fees at Research Council rates for 3.5 years.
Location: Streatham Campus, University of Exeter, EX4 4QJ
Secondary supervisors: Professor Krasimira Tsaneva-Atanasova (University of Exeter), Professor Andrew Randall (University of Exeter)
The production of action potentials is a defining feature of the functional physiology of all excitable cells. Typically, only after firing a spike will a cell perform its task and, furthermore, the rate, timing and patterns of spike generation have important
effects on the nature of the downstream events they trigger, for example neurotransmitter release. Hence, quantifying the characteristic features of action potential production in neurons is crucial in helping us to understand the normal functional physiology
of nervous systems, as well as how these are altered during pathological conditions associated with disease.
Based within the EPSRC Centre for Predictive Modelling in Healthcare, a £2M initiative bringing together mathematicians, statisticians and clinicians, you will work on a project aiming to develop in silico biophysical models of neural excitability in the mammalian
nucleus reuniens (NRe). This area within the thalamus is receiving increased attention from neuroscientists, (including both the 2013 and 2014 Nobel Laureates in Physiology and Medicine; see Xu and Sudhoff (2013), Science 339, 1290-5 and Ito et al. (2015)
Nature 522, 50-5). Through its robust connectivity to structures such as the hippocampus and prefrontal cortex, this midline thalamic nucleus is involved in both spatial and cognitive processing. It is also a key site of pathology in Korsakoff’s syndrome (aka
amnesic-confabulatory syndrome), a form of dementia. Recent ongoing work in the Randall lab at Exeter has generated a large body of novel electrophysiological data that details the core electrical excitability of neurons in the nucleus reuniens, in both normal
adult animals and rodent disease models. These datasets are supported by additional biophysical characterisations of the gating of some of the key underpinning ion channels in NRe neurons. These experimental data will form the basis for the computational models
that this project will generate, models that will probe the mechanisms that govern the physiological spiking and bursting dynamics of NRe cells. The ultimate goal is to both better understand normal physiological NRe function, and to identify possible interventional
routes through which abnormal NRe activity observed in disease models can be normalised toward the neurophysiological signatures presented by healthy tissue. Mathematical analysis and numerical/computational techniques will be applied to study the behaviour
of the system in normal and pathological conditions. The computational component of the project will include the use of multi-objective evolutionary algorithms to optimise the parameters of the model to data, and the use of bifurcation analysis software.
Application Criteria
Applicants should have or expect to achieve a 2:1 Honours degree, or equivalent, in Mathematics, Physics, Natural Sciences, Medicine or other numerate discipline.
The closing date for applications if midnight on 4 January, 2016. Interviews will be held at the University of Exeter mid-late January, 2016.
For further information, or an informal discussion about the position, please contact Dr Ozbur Akman, e-mail:
O.E.Akman@exeter.ac.uk.