PhD: Locomotor and Respiratory Pattern Generators

The University of St Andrews seeks a PhD student to map the descending and ascending pathways that control walking and breathing circuits, and how they are disrupted in ALS, on a funded four-year EASTBIO PhD with Dr Ilary Allodi and Prof Gareth Miles.

Background: Rhythmic movements such as walking and breathing are generated by central pattern generators (CPGs) which are dedicated neuronal networks within the spinal cord and brainstem. While the intrinsic organisation of these CPGs is increasingly well understood, several questions remain unanswered about how they are controlled by descending pathways from supraspinal centres and modulated by ascending sensory and proprioceptive feedback. This gap is particularly important in the context of motor neuron disorders such as ALS, where degeneration is not confined to motor neurons themselves but also affects the premotor circuits and long-range pathways that coordinate locomotor and respiratory output. Thus, understanding how these pathways shape CPG function, and how their disruption contributes to disease progression, is essential.

Aims: This project will map and functionally characterise the descending and ascending pathways that regulate locomotor and respiratory CPGs. Specific aims are to: (1) anatomically trace descending and ascending connections onto CPG neurons using viral and tissue-clearing approaches; (2) determine the functional contribution of identified pathways using in vivo Ca2+ imaging, as well as optogenetic and chemogenetic manipulation; (3) assess circuit-level changes with locomotor and respiratory behaviour; and (4) correlate how these pathways may be altered in disease.

Approach: The project combines anatomical, functional and behavioural techniques. Circuit tracing will be performed using retrograde/anterograde viral tools combined with tissue clearing and imaging, generating large 3D datasets analysed with advanced, semi-automated image-analysis pipelines. Functional interrogation of identified pathways will use in vivo calcium imaging to monitor pathway activity during behaviour, alongside optogenetics and chemogenetics to selectively activate or silence specific projections. Locomotor and respiratory behaviour will be quantified using markerless, machine-learning-based tracking and classification, allowing high-resolution, unbiased analysis of motor output.

Significance and training: The student will acquire an integrated skill set spanning viral tracing, tissue clearing, large-scale image analysis, in vivo imaging, optogenetics, chemogenetics and machine-learning-based behavioural quantification. The project bridges anatomy, circuit physiology and behaviour to address a fundamental open question in motor control, with direct relevance to understanding circuit-level vulnerability in disease.

HOW TO APPLY

Application instructions can be found on the EASTBIO website- How to Apply | EastBio Doctoral Training Partnership | Biology

1) Download and complete the Equality, Diversity and Inclusion survey.

2) Download and complete the EASTBIO Application Form.

3) Please complete an application on our online portal: How to apply – Study at St Andrews – University of St Andrews

4) Select the course ‘PhD with internship’

5) Your online application must include the following documents:

• Completed EASTBIO application form
• Academic Qualifications
• English Language Qualification (if applicable)
• 2 References: this must be completed on the EASTBIO Reference Form, also found on the EASTBIO website.

Please download the EASTBIO reference form and send it to your referees. They can either upload it directly to the portal using the automated email they will receive, or they can email it to Rachel at pgrecbiology@st-andrews.ac.uk

CONTACT

Queries on the project can be directed to the project supervisor.

Queries on the application process can be directed to Rachel Horn at pgrecbiology@st-andrews.ac.uk

UKRI eligibility guidance: Terms and Conditions: View Website International/EU: View Website

Funding Notes

This 4 year PhD project is part of a competition funded by EASTBIO BBSRC Doctoral Training Partnership.

This opportunity is open to UK and International students and provides funding to cover stipend at UKRI standard rate and UK level tuition fees. The University of St Andrews will cover the Home-International fee difference.