The neuronal sodium-activated potassium channel KNa1.1 (KCNT1, Slack) couples sodium influx to changes in membrane excitability and action potential firing. Dysfunction of this ion channel in humans causes intellectual disability and severe epilepsy, for which there is no treatment, making it a potential therapeutic target for a range of neurological conditions. Despite its importance in health and disease, many aspects of its function remain poorly understood. The aim of this project is to develop a molecular understanding of how sodium ions bind to the protein, and how this causes conformational changes that result in channel opening. Structural analysis involving cryo-EM data and molecular dynamics simulations will be used to understand the molecular basis of channel activation. These structural models will be evaluated and refined experimentally by site-directed mutagenesis, electrophysiological measurements, and by identifying state-specific ligands.
Applications are especially welcome and encouraged from groups that are under-represented in science and academia.
Keywords: Ion channels, membrane proteins, structural biology, molecular dynamics simulations, structure-based drug-design, protein mechanism
Eligibility:
You should be a UK-based applicant (due to funding constraints) and hold a first degree equivalent to at least a UK upper-second class honours degree or a MSc degree in a relevant subject. This project would suit someone with a strong interest in neuroscience, ion channel biology, or membrane protein structure and function.
Applications are especially welcome and encouraged from groups that are under-represented in science and academia.
Funding Note
This opportunity is funded by a project grant and the appointed candidate will be fully-funded for 4 years. The funding includes:
Tax-free annual UKRI stipend (£15,840 for 2022/23 starts. Awards increase every year, typically with inflation).
UK tuition fees (Around £4,600 per year)
How to apply
Applicants should complete an online application form and attach the following documentation to support their application.
- a full academic CV
- degree certificate and transcripts of marks
- Evidence that you meet the University's minimum English language requirements (if applicable).
To help us identify that you are applying for this studentship project please ensure you provide the following information on your application form;
- Select PhD in Biological Sciences as your programme of study
- Give the full project title and name the supervisors listed in this advert
- For source of funding please state "BBSRC White Rose DTP"
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