Back to search results

PhD Studentship: Investigating the Biological Basis of Sex Differences in Nociceptor Excitability with Age-related Joint Degeneration

London Interdisciplinary Biosciences Consortium - William Harvey Research Institute, Queen Mary, University of London

Qualification Type: PhD
Location: London
Funding for: UK Students, EU Students, International Students
Funding amount: £20,622 per annum
Hours: Full Time
Placed On: 20th October 2023
Closes: 10th January 2024

This PhD aims to determine the biological basis of sex specific mechanisms of nociceptor hyperexctaibility in age-related joint degeneration. The proposal addresses the biology of ageing, the long-term condition of joint degeneration and the consequent burden of pain, which fit the BBSRC remit of ‘securing better health, ageing and wellbeing.’ 

Ageing is associated with joint degeneration that can lead to increased excitability of articular nociceptors and consequent pain. However, the impact of ageing itself on the excitability of articular nociceptors is unknown. Moreover, females are at higher risk of age-related joint degeneration, although mechanisms underlying sex differences in associated pain sensitivity are unclear. 

A major hurdle in effective translation of preclinical studies addressing the biology of age-related joint degeneration is the availability of clinically relevant rodent models. Preliminary data generated in our lab demonstrates that the menisco-ligamentous injury model in mice leads to substantial cartilage loss and behavioural hypersensitivity (to mechanical and cold stimuli), which mimics the clinical picture of age-related joint degeneration and associated changes in pain sensitivity, in a sex dependent manner. 

The rationale of this project is based on 2 overarching questions: (1) How does age-related joint degeneration cause increased pain sensitivity and sex differences in pain? Pain sensitivity may be mediated by hyperexcitable nociceptors that innervate the degenerative joint (e.g. subchondral bone), or through cross talk of primary sensory neurons (e.g. through gap junctions in dorsal root ganglia). (2) Can modulation of the neuro-immune axis affect nociceptor excitability mediated by age-related joint degeneration? We will test the hypothesis that targeting the neuro-immune axis can modulate nociceptor excitability in age-related joint degeneration, either directly or indirectly via inter-cellular communication. 

Key techniques will involve in vivo microCT imaging for bone morphology, In vitro calcium imaging of primary sensory neurons, immunophenotyping and cell sorting, as well as pain behaviour assays and the use of transgenic mice for in vivo studies. This PhD is an iCASE studentship in collaboration with GSK. 

Aim 1. Determine whether bone morphological changes with age-related joint degeneration drive sex differences in the development of pain sensitivity. 

Aim 2. Determine whether sex differences in pain sensitivity following age-related joint degeneration are mediated directly by changes in neuronal excitability of articular afferents or via neuro-immune cross-talk within dorsal root ganglia 

Aim 3. Test the mechanistic role of specific immune cells on articular nociceptor hyperexcitability in age-related joint degeneration

We value your feedback on the quality of our adverts. If you have a comment to make about the overall quality of this advert, or its categorisation then please send us your feedback
Advert information

Type / Role:

Subject Area(s):

Location(s):

PhD tools
 

PhD Alert Created

Job Alert Created

Your PhD alert has been successfully created for this search.

Your job alert has been successfully created for this search.

Ok Ok

PhD Alert Created

Job Alert Created

Your PhD alert has been successfully created for this search.

Your job alert has been successfully created for this search.

Manage your job alerts Manage your job alerts

Account Verification Missing

In order to create multiple job alerts, you must first verify your email address to complete your account creation

Request verification email Request verification email

jobs.ac.uk Account Required

In order to create multiple alerts, you must create a jobs.ac.uk jobseeker account

Create Account Create Account

Alert Creation Failed

Unfortunately, your account is currently blocked. Please login to unblock your account.

Email Address Blocked

We received a delivery failure message when attempting to send you an email and therefore your email address has been blocked. You will not receive job alerts until your email address is unblocked. To do so, please choose from one of the two options below.

Max Alerts Reached

A maximum of 5 Job Alerts can be created against your account. Please remove an existing alert in order to create this new Job Alert

Manage your job alerts Manage your job alerts

Creation Failed

Unfortunately, your alert was not created at this time. Please try again.

Ok Ok

Create PhD Alert

Create Job Alert

When you create this PhD alert we will email you a selection of PhDs matching your criteria.When you create this job alert we will email you a selection of jobs matching your criteria. Our Terms and Conditions and Privacy Policy apply to this service. Any personal data you provide in setting up this alert is processed in accordance with our Privacy Notice

Create PhD Alert

Create Job Alert

When you create this PhD alert we will email you a selection of PhDs matching your criteria.When you create this job alert we will email you a selection of jobs matching your criteria. Our Terms and Conditions and Privacy Policy apply to this service. Any personal data you provide in setting up this alert is processed in accordance with our Privacy Notice

 
 
 
More PhDs like this
Join in and follow us

Browser Upgrade Recommended

jobs.ac.uk has been optimised for the latest browsers.

For the best user experience, we recommend viewing jobs.ac.uk on one of the following:

Google Chrome Firefox Microsoft Edge