Centre for Physical Activity and Life Sciences (PALS)
Catch-up with the latest news, information, research and contacts for the Science department in their newsletter: Issue 1
What is the Centre for Physical Activity and Life Sciences?
The Research Centre aims to:
- Bring together researchers examining physiological, psychological and biomechanical aspects of physical activity interventions in sedentary, active and clinical populations, and the microbiological, genetic and molecular aspects of disease.
- Develop research capacity by providing training and mentorship opportunities for undergraduate to postdoctoral researchers and supporting early career researchers to become independent research leaders targeting national and global challenges to health.
Areas of interest:
The Centre for Physical Activity and Life Sciences is a multidisciplinary Centre including expertise in Biosciences, Sport & Exercise Sciences, Podiatry, Physiotherapy and Occupational Therapy. The Centre includes two main Research Groups (Molecular Biosciences Research Group and Neuromusculoskeletal Research Group).
We are currently accepting self-funded PhD students within all areas of expertise of the researchers in these Groups outlined below:
- Molecular Biosciences Research Group
- Genetics of complex diseases
- Clinical genomics
- RNA-based gene therapy
- Neurological and ovarian cancers
- Duchenne muscular dystrophy
- Monozygotic twin studies
- Applied microbiology
- Antimicrobial resistance
- Molecular Mechanisms of Bacterial Pathogenesis
- Infection control
- Neuromusculoskeletal Research Group
- Functional decline in ageing and fall risk
- Sarcopenia and osteoporosis
- Eccentric exercise in healthy and ageing populations
- Cognitive impairment and balance in ageing
- Muscle stretching techniques and strain injury
- Isometric resistance training and hypertension
- Stroke rehabilitation
- Concussion in impact sports
- Centre Lead
Professor Tony Kay
- Biosciences Lead
Associate Professor Lee Machado
- Biosciences Lead
Associate Professor Karen Anthony
- Neuromusculoskeletal Lead
Dr Tony Baross
Working with the Centre
If you are interested in working with the Centre for Physical Activity and Life Sciences, please contact email@example.com.
Neuropathophysiology of Duchenne muscular dystrophy and the RNA processing of the major brain dystrophin protein, Dp71
This project is funded by the French Muscular Dystrophy Association (AFM-Telethon) and is led by Dr Karen Anthony. Duchenne muscular dystrophy is a fatal childhood genetic disorder. It is caused by the body-wide absence of a muscle protein called dystrophin. Alongside muscle symptoms; the loss of dystrophin in the brain leads to intellectual disability and conditions like autism. This work aims to build a deeper understanding of the production and function of dystrophin in the brain to inform the development of brain-targeting treatments.
- Naidoo M, Anthony K. (2020). Dystrophin Dp71 and the neuropathophysiology of Duchenne muscular dystrophy. Molecular Neurobiology. 57:1748-1767.
- Ash A, Machado L, Raleigh S, Anthony K. (2018). Neuropathophysiology of Duchenne muscular dystrophy: involvement of the dystrophin isoform Dp71 in cell migration and proliferation. Neuromuscular Disorders. 28(Supp 1):S13-S14. 11th Annual Neuromuscular Translational Research Conference, Cambridge, UK.
- Ash A, Booth-Wynne L, Anthony K. (2017). Brain involvement in Duchenne muscular dystrophy: A role for dystrophin isoform Dp71 in cell migration and proliferation. Neuromuscular Disorders. 27(Supp 2):S114-S115. 22nd International Congress of the World Muscle Society, Saint Malo, France.
Investigating the role of the Duchenne muscular dystrophy-associated protein, dystrophin, in cancer
Dr Karen Anthony and Dr Lee Machado lead several projects focused on the contention that dystrophin proteins appear to play a poorly defined role in cancer. These projects take advantage of cancer genome discovery data, human tissue and cancer cell lines to elucidate the relationships and mechanisms between dystrophin expression and cancer progression.
- Jones L, Naidoo M, Machado L, Anthony K. (2020). The Duchenne muscular dystrophy gene and cancer. Cellular Oncology. https://doi.org/10.1007/s13402-020-00572-y
Effects of eccentric plantarflexor and dorsiflexor training on neuromuscular characteristics associated with fall risk in older people
This project is led by Professor Tony Kay and aims to examine the efficacy, adherence and tolerance to seated isokinetic eccentric exercise in older people. Specific emphasis is on the training and detraining effects of eccentric exercise on fall risk factors including muscle strength, mass, balance and mobility to promote healthy ageing and reverse neuromuscular functional decline.
- Kay AD, Blazevich AJ, Fraser M, Ashmore L, Hill MW. (2020). Isokinetic eccentric exercise substantially improves mobility, muscle strength and size, but not postural sway metrics in older adults, with limited regression observed following a detraining period. Eur J Appl Physiol. 120:2383-2395.
- Pinto MD, Wilson C, Kay AD, Cochrane J, Blazevich AJ. (2019). The effect of isokinetic dynamometer deceleration phase on maximum ankle joint range of motion and plantar flexor mechanical properties tested at different angular velocities. J Biomech. 92:169-174.
- Hill MW, Duncan MJ, Oxford SW, Kay AD, Price MJ. (2018). Effects of external loads on postural sway during quiet stance in adults aged 20–80 years. Appl Ergo. 66:64-69.
- Roberts M, Talbot C, Kay A, Price M, Hill M. (2018). Changes in postural sway and gait characteristics as a consequence of anterior load carriage. Gait Posture. 66:139-145.
- Kay AD, Rubley B, Talbot C, Mina MA, Baross AW, Blazevich AJ. (2018). Stretch imposed on active muscle elicits positive adaptations in strain risk factors and exercise-induced muscle damage. Scand J Med Sci Sports. 28(11):2299-2309.
Fc receptor genetics and disease
This project is led by Dr Lee Machado who is working with David Young and Ed Hollox to better understand how the genetics of the high and low affinity Fc receptors for IgG antibodies may be associated with disease and patient outcomes including autoimmune diseases and Sepsis.
- Rahbari R, Zuccherato LW, Tischler G, Chihota B, Ozturk H, Saleem S, Tarazona-Santos E, Machado LR, Hollox EJ. (2017). Understanding the Genomic Structure of Copy-Number Variation of the Low-Affinity Fcγ Receptor Region Allows Confirmation of the Association of FCGR3B Deletion with Rheumatoid Arthritis. Human Mutation. 38(4):390-399.
- Hargreaves CE, Iriyama C, Rose-Zerilli MJJ, Nagelkerke SQ, Hussain K, Ganderton R, Lee C, Machado LR, et al. (2015). Evaluation of High-Throughput Genomic Assays for the Fc Gamma Receptor Locus. A. Haziot, ed. PloS One. 10(11):e0142379.
Antisense oligonucleotide-mediated exon skipping as a therapy for Duchenne muscular dystrophy (DMD)
Dr Karen Anthony is an active member of the European Cooperation in Science and Technology (COST) action on Delivery of Antisense RNA Therapeutics. We are involved in ongoing projects that aim to expedite the development of candidate exon skipping drugs through the clinic. Working with Professor Francesco Muntoni, Dr Anthony played a key role in the early development of Exondys 51™, the first FDA-approved drug for DMD. A current focus is on overcoming barriers to efficient delivery to target tissues such as the brain.
- Hiller M, Falzarano MS, Garcia-Jimenez I, Sardone V, Verheul RC, Popplewell L, Anthony K, et al. (2018). A multicenter comparison of quantification methods for antisense oligonucleotide-induced DMD exon 51 skipping in Duchenne muscular dystrophy cell cultures. PLOS One. 13(10):e0204485.
- Anthony K, Arechavala-Gomeza V, Ricotti V, Torelli S, Feng L, Janghra N, … Muntoni, F. (2014). Biochemical characterization of patients with in-frame or out-of-frame DMD deletions pertinent to exon 44 or 45 skipping. JAMA Neurol. 71(1):32-40.
- Cirak S, Feng L, Anthony K, Arechavala-Gomeza V, Torelli S, Sewry C, … Muntoni, F. (2012). Restoration of the dystrophin-associated glycoprotein complex after exon skipping therapy in Duchenne muscular dystrophy. Mol Ther. 20(2):462-467.
- Anthony K, Cirak S, Torelli S, Tasca G, Feng L, Arechavala-Gomeza V, … Muntoni, F. (2011). Dystrophin quantification and clinical correlations in Becker muscular dystrophy: implications for clinical trials. Brain. 134(12):3547-3559.
- Cirak S, Arechavala-Gomeza V, Guglieri M, Feng L, Torelli S, Anthony K, … Muntoni F. (2011). Exon skipping and dystrophin restoration in patients with Duchenne muscular dystrophy after systemic phosphorodiamidate morpholino oligomer treatment: an open-label, phase 2, dose-escalation study. Lancet. 378(9791):595-605.
Tolerance of oxidative and metal stresses in Streptococcus pneumoniae: transcriptional responses and novel mechanisms
- PhD student: Lewis Waterfield
- First supervisor: Dr Alex Woodacre
- Second supervisor: Dr Jodie Score
This project aims to characterise the ways in which S. pneumoniae responds to different toxic environments within the human host and therefore how it survives to cause disease. Particular emphasis is on the combination of copper and oxygen used to kill bacteria in macrophages and the bacterial response to host iron sources such as haemoglobin.
- Glanville DG, Han L, Maule AF, Woodacre A, Thanki D, Abdullah IT, et al. (2018). RitR is an archetype for a novel family of redox sensors in the streptococci that has evolved from two-component response regulators and is required for pneumococcal colonization. PLoS Pathog. 14(5):e1007052.
Effects of Isometric Resistance Training on Ambulatory Blood Pressure and Morning Blood Pressure Surge in Young Normotensive Men and Women
This project is led by Dr Tony Baross and aims to examine the impact of isometric exercise in young adult normotensive people. Specific emphasis is on the effects on morning blood pressure surge which is associated with an increased risk of cardiovascular events.
- Smart NA, Way D, Carlson D, Millar P, McGowan C, Swaine I, Baross A, et al. (2019). Effects of isometric resistance training on resting blood pressure: individual participant data meta-analysis. J Hypertension. 37(10):1927-1938.
- Baross AW, Somania Y, Brook RD, Milne K, McGowan C and Swaine I. (2017). Acute Response to a 2-Minute Isometric Exercise Test Predicts the Blood Pressure-Lowering efficacy of Isometric Resistance Training in Young Adults. Am J Hypertension. 31(3):362-368.
- Baross AW, Hodgson DA, Padfield SL, and Swaine IL. (2017). Reductions in Resting Blood Pressure in Young Adults When Isometric Exercise Is Performed Whilst Walking. J Sports Med. 2017:7123834.
- Baross AW, Somania Y, Levy P, Zinszer K, Milne K, Swaine I and McGowan C. (2017). Reductions in ambulatory blood pressure in young normotensive men and women after isometric resistance training and its relationship with cardiovascular reactivity. Blood Pressure Monitoring J. 22:1-7.
Genetics of complex diseases and traits
These projects are led by Dr. Jamal Nasir and aim to investigate the genetics of complex diseases and traits, including COVID-19. Using a combination of dry (bioinformatics) and wet lab approaches, the identification of genes underlying neurodevelopmental, cardiovascular and other diseases, including COVID-19 and the related disease mechanisms are the main priorities.
- Salim S, Nasir J, Chen PE. (2019). Overexpression of the dopamine receptor-interacting protein Alix/AIP1 modulates NMDA receptor triggered cell death. Febs Letters. 593(12):1381-1391.
- Jelani M, Dooley HC, Gubas A, Mohamoud HSA, Khan MTM, … Nasir J. (2019). A mutation in the major autophagy gene, associated with global developmental abnormalities. Brain. 142(5):1242 -1254.
- Vadgama N, Lamont D, Hardy J, Nasir J, Lovering RC. (2019). Distinct proteomic profiles in monozygotic twins discordant for ischaemic stroke. Mol Cell Biochem. 456:157-165.
- Vadgama N, Pittman A, Simpson M, Nirmalananthan N, Murray R, Yoshikawa T, … Nasir J. (2019). De novo single-nucleotide and copy number variation in discordant monozygotic twins reveals disease related genes. Eur J Human Genetics. 27(7):1121-1133.
- Mohamoud HS, Ahmed S, Jelani M, Alrayes N, Childs K, Vadgama N, … Nasir J. (2018). A missense mutation in TRAPPC6A leads to build-up of the protein, in patients with a neurodevelopmental syndrome and dysmorphic features. Scientific Reports. 8(1):2053.