Research
Loss of muscle mass and function and defective regeneration of skeletal muscle during ageing and disease
Epigenetic events, such as DNA methylation, chromatin remodelling or microRNA-mediated regulation of gene expression play a key role during organism development, life and ageing. Our research is focused on the phenomenon of gene and chromatin regulation by microRNAs and the role of these mechanisms in maintaining muscle homeostasis. We use both high-throughput and focused approaches, as well as in vitro and in vivo model systems to decipher the role of epigenetic changes and microRNA:target interactions during muscle regeneration and ageing.
This strand of research is funded by BBSRC and Dunhill Medical Trust Research grants.
The role of microRNAs in tendon injury
This research investigates:
1) How cells in a specific part of tendon which is vital for tendon function, alter their behavior in disease, and how this altered behavior is controlled by a class of recently discovered small genes known as microRNAs.
2) Can we reverse the disease changes in these tendon cells by altering levels of these specific small genes (microRNAs) to improve healing of tendons after injury?
This project will use the state-of-the-art techniques (sequencing and computer based approaches) to identify the most promising microRNAs and determine how they may be altered in tendon injury. We will then confirm the role of the microRNAs which we think are important through undertaking experiments where we alter the levels of specific microRNAs in lab based cell culture experiments. This will identify specific targets which we can develop into novel treatments for tendon injuries.
This project is funded by Orthopaedic Research UK.
The role of microRNAs in neuromuscular interactions in ageing and disease
Irreversible muscle wasting occurs during amyotrophic lateral sclerosis (motor neuron disease; ALS) and ageing (sarcopenia). Loss of skeletal muscle mass and strength is characterised by muscle fibre atrophy (decreased muscle size) and reduced muscle function linked to deterioration of the muscle:nerve communication. Muscle loss leads to poor balance, falls and fractures and increased morbidity and mortality in older people and ALS patients. There is no cure for muscle wasting. Therefore, it is important to identify the mechanisms responsible for muscle loss related to changes in muscle:nerve interactions. The molecular factors responsible for muscle wasting are not fully understood, however there is increasing evidence that microRNAs might have a significant role to play.
MicroRNAs (miRNAs, miRs) are small RNA molecules that regulate gene expression. Each microRNA is predicted to regulate the levels of up to several hundred genes. Expression of many microRNAs and their targets changes with age or in diseases. This makes microRNAs very strong candidates for therapeutic targets for muscle wasting, for example by controlling their levels by using molecules that mimic their behaviour.
We are identifying microRNA:target interactions that change during age- and ALS-related loss of muscle mass and strength and establish the function of these microRNAs. We will examine whether using molecules to increase or decrease the levels of microRNAs have potential therapeutic applications for muscle wasting through preserving muscle:nerve interactions.
Research grants
microRNA-based interventions against loss of muscle mass and function resulting from in utero and early post-natal protein restriction
BIOTECHNOLOGY & BIOLOGICAL SCIENCE RESEARCH COUNCIL
May 2017 - April 2020
Reverse engineering glaucoma: Progress toward the integrative genomics of glaucoma
UK AND EIRE GLAUCOMA SOCIETY (IRELAND)
February 2016 - August 2019
The role of microRNA:target interactions in tendon function deterioration
ORTHOPAEDIC RESEARCH UK (UK)
October 2016 - September 2019
2014 allocation - Wellcome ISSF non clinical fellowships
WELLCOME TRUST (UK)
May 2015 - October 2018
Do age-related changes in microRNA expression in muscle mediate sarcopenia?
BIOTECHNOLOGY & BIOLOGICAL SCIENCE RESEARCH COUNCIL
July 2014 - February 2018
Research collaborations
Dr. Ilaria Bellantuono
miRs in musculoskeletal ageing
University of Sheffield
The potential of microRNAs against age-related musculoskeletal disorders.
Dr. Brian McDonagh
miRsa dn redox homeostasis in muscle ageing
National University of Ireland, Galway
Investigating interaction between miRs and ROS during muscle wasting.
Prof. N. Deutz, Prof. M. Engelen
miRs in muscle wasting
Texas A&M University
Investigating the potential of microRNAs as biomarkers of muscle wasting in ageing and disease