About the Project
This project is one of a number that are in competition for funding from the ‘GW4 BioMed MRC Doctoral Training Partnership’ which is offering up to 17 studentships for entry in October 2021.
+++ Note: Full funding may not be available for all applicants. Please see the Funding Notes below for more information +++
The DTP brings together the Universities of Bath, Bristol, Cardiff and Exeter to develop the next generation of biomedical researchers. Students will have access to the combined research strengths, training expertise and resources of the four research-intensive universities. More information may be found here: https://www.gw4biomed.ac.uk/.
SUPERVISORY TEAM:
Prof Alain Nogaret (lead), University of Bath, Department of Physics https://researchportal.bath.ac.uk/en/persons/alain-nogaret
Dr Jon Brown, University of Exeter, College of Medicine and Health
Dr Kyle Wedgwood, University of Exeter, College of Engineering, Mathematics and Physical Sciences, Living Systems Institute
THE PROJECT:
Neurons display a wide range of electro-responsive properties which depend on the expression of a range of distinct voltage-gated ion channels. Estimating the microscopic parameters of these ion channels is critically important to build a quantitative understanding of the effects of neurodegenerative disease on neurons’ electrical output and subsequently to design drugs with improved efficiency. We aim to estimate the parameters that govern ion channel kinetics, activation and inactivation thresholds and ionic conductances. They are responsible for the alterations in channel activity in Alzheimer disease, Parkinson disease, Rett syndrome, epilepsy, and autism.
Whilst knowledge of these parameters facilitates quantitative understanding of neural response, it is difficult to estimate them because many are hidden from observation. In recent years, powerful data assimilation methods have been developed to infer the full complement of ion channels from time series current-clamp recordings. The Bath group has spearheaded this effort by building quantitative models that predict the behaviour of songbird neurons (Sci. Rep. 6, (2016) 32749), of hippocampal and respiratory neurons (Nature Comm. 10 (2019) 5309) and by incorporating these models in chip implants that reverse the effects of heart failure (J. Physiol. 598 (2020) 455).
This project will build on the recent advances of the Bath team and on the expertise of the Exeter team in patch-clamping small networks of healthy and diseased neurons. The student will be based in the Physics department at Bath and will visit the Living Systems Institute at Exeter to acquire electrophysiological recordings of CA1 neurons in brain slices prepared from transgenic mouse models of Alzheimer’s disease. In Bath, the PhD student will compute ion channel parameters from the membrane voltage recordings of healthy and diseased neurons to quantify the changes introduced by Alzheimer’s disease pathology at the level of individual ion channels. Models completed with the extracted parameters will allow us to predict the behaviour of diseased neurons and to understand the effect of drugs on them via simulation. Once validated, the quantitative model will be used to optimise drugs to restore normal function in Alzheimer neurons.
APPLICATIONS:
Applicants must have obtained, or be about to obtain, a First or Upper Second Class UK Honours degree, or the equivalent qualifications gained outside the UK. We welcome applications from theoretical and computationally-minded students who have studied Maths and Physics, Natural Sciences or Physics and have an interest in applying mathematical models to neuroscience.
IMPORTANT: In order to apply for this project, you should apply using the DTP’s online application form: https://cardiff.onlinesurveys.ac.uk/gw4-biomed-mrc-doctoral-training-partnership-student-appl-2
You do NOT need to apply to the University of Bath at this stage – only those applicants who are successful in obtaining an offer of funding form the DTP will be required to submit an application to study at Bath.
More information on the application process may be found here:
https://www.gw4biomed.ac.uk/doctoral-students/
APPLICATIONS CLOSE AT 17:00 ON 23 NOVEMBER 2020.
Funding Notes
Studentships cover tuition fees at the ‘Home’ level, research/training costs and a stipend (£15,285 p.a., 2020/21 rate) for 3.5 years.
The main categories of candidates normally eligible for 'Home' fees are:
UK nationals*
Irish nationals living in the UK/Ireland
Applicants with settled or pre-settled* status in the UK under the EU Settlement Scheme
Applicants with indefinite leave to enter/remain in the UK
* must have lived in the UK/EEA/Switzerland continuously since September 2018.
Those not meeting the nationality and residency requirements to be treated as a ‘Home’ student may apply for a limited number of full studentships for international students.