BBSRC NLD Doctoral Training Partnership: Understanding mechanisms of ageing and muscle weakness utilizing omics and bioinformatics

Anabolic resistance refers to the reduced responsiveness of skeletal muscle to robust muscle-building stimuli like resistance exercise and muscle-enhancing foods as individuals age. This diminished response is considered a significant factor contributing to the age-related loss of skeletal muscle, known as sarcopenia. Intriguingly, not all older individuals display the same extent of anabolic resistance, as demonstrated by the research conducted by supervisors 1 and 4. Additionally, A healthy gut can support muscle function by generating postbiotics, such as short-chain fatty acids (SCFA) and Urolithin A (UA). Both UA and SCFA are suggested to enhance mitochondrial function and reduce excessive inflammation, key factors for maintaining muscle function and health in older age. Interestingly, not everyone possesses a microbiome capable of producing postbiotics, making postbiotics an appealing strategy for overcoming anabolic resistance—a fundamental aspect of the gut-muscle relationship.

In 'Work Package 1,' we propose that anabolic resistance is also related to how muscles metabolically respond. Our goal is to categorize individuals based on their response to muscle stimuli, distinguishing those who exhibit robust strength gain and muscle growth ('responders') from those who do not ('anabolic resistance'). These categorizations will provide valuable models for studying potential mechanisms that are challenging to explore directly in human subjects.

Our experimental approach involves employing bioinformatic analyses to unravel the mechanisms behind anabolic resistance to exercise in older adults. The primary supervisor and the team have recently gathered extensive metabolomic data from muscle biopsies of older participants, collected before and after leg resistance exercise, funded by the BBSRC. This data has enabled the characterization of the group experiencing anabolic resistance, showing up to a 40% lower hypertrophy response to exercise as measured by MRI compared to the 'responders.' The subsequent focus of this project is on integrated bioinformatic analyses, studying molecular pathways and identifying candidate metabolites.

In 'Work Package 2,' we hypothesize that postbiotics, such as UA and SCFAs can overcome anabolic resistance. Our experimental approach involves studying the effects of postbiotics like UA and SCFAs on human myoblasts (MB) in vitro, isolated from both younger and older human participants categorized as 'responders' and 'anabolic resistance,' before and after resistance exercise. We'll utilize various molecular assays to assess the impact on mitochondrial metabolism, reactive oxygen species production, target gene/protein biomarkers, and the metabolites identified in the first phase of experiments.

HOW TO APPLY

Applications should be made by emailing bbsrcdtp@liverpool.ac.uk with:

• a CV (including contact details of at least two academic (or other relevant) referees);
• a covering letter – clearly stating your first-choice project, and optionally 2nd ranked project, as well as including whatever additional information you feel is pertinent to your application; you may wish to indicate, for example, why you are particularly interested in the selected project(s) and at the selected University;
• copies of your relevant undergraduate degree transcripts and certificates;
• a copy of your passport (photo page).

A GUIDE TO THE FORMAT REQUIRED FOR THE APPLICATION DOCUMENTS IS AVAILABLE AT https://www.nld-dtp.org.uk/how-apply. Applications not meeting these criteria may be rejected.

In addition to the above items, please email a completed copy of the Additional Details Form (as a Word document) to bbsrcdtp@liverpool.ac.uk. A blank copy of this form can be found at: https://www.nld-dtp.org.uk/how-apply.

Informal enquiries may be made to masoudi@liverpool.ac.uk

The deadline for all applications is 12noon on Monday 22nd July 2024. 

Part-Time Study Options

All NLD DTP PhDs are available as part time or full time, with part time being a minimum of 50% of full time. Please discuss potential part time arrangements with the primary supervisor before applying to the programme.

Project CASE Status

This project is not a CASE project. While individual applicant quality is our overriding criterion for selection, the NLD DTP has a commitment to fund 8 CASE projects per year - as such, CASE projects may be favoured in shortlisting applicants when candidates are otherwise deemed to be equal or a consensus on student quality cannot be reached.