Centre for Physical Activity and Life Sciences (PALS)

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 progression.
  • Develop research capacity by providing training 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, and Occupational Therapy.  The Centre includes two main Research Groups (Molecular Biosciences Research Group, Neuromuscular and Musculoskeletal Research Group) with the main interests of researchers in these Groups outlined below:

  • Molecular Biosciences Research Group
    • Immunogenetics
    • Clinical genetics and genomics
    • RNA-based gene therapy
    • Cancer biology
    • Neuromuscular and neurodegenerative disorders
    • Monozygotic twin studies
    • Bioethics
    • Antimicrobial resistance
    • Molecular Mechanisms of Bacterial Pathogenesis
    • Infection control
  • Neuromuscular and Musculoskeletal Research Group
    • Functional decline during ageing and fall risk
    • Sarcopenia and osteoporosis
    • Eccentric exercise in healthy and ageing populations
    • Cognitive impairment, pain and balance in ageing
    • Muscle stretching techniques and strain injury
    • Isometric resistance training and hypertension
    • Exercise-induced muscle damage
    • Heat- and cryo-based therapy
    • Stroke rehabilitation
    • Concussion in impact sports

Centre Staff

Staff leading the Centre include:

Role Name Telephone
Centre Lead Professor Tony Kay +44(0)1604 892577
Biosciences Lead Dr Lee Machado +44(0)1604 893476
Biosciences Lead Dr Karen Anthony +44(0)1604 893467
Musculoskeletal Lead Dr Tony Baross +44(0)1604 892143

Projects

Investigating the role of dystrophin in cancers

This project involves Dr Karen Anthony, Dr Lee Machado and Michael Naidoo and focuses on the3 contention that dystrophin appears to play a poorly defined role in cancer.  This project takes advantage of cancer genome discovery data, tissue microarrays and cancer cell lines to elucidate the relationships between dystrophin expression and cancer.

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.

Selected Outputs:

  • Hargreaves, C.E., Iriyama, C., Rose-Zerilli, M.J.J., Nagelkerke, S.Q., Hussain, K., Ganderton, R., Lee, C., Machado, L.R., … Strefford, J.C. (2015) Evaluation of High-Throughput Genomic Assays for the Fc Gamma Receptor Locus. A. Haziot, ed. PloS one. 10(11), e0142379.
  • Rahbari, R., Zuccherato, L.W., Tischler, G., Chihota, B., Ozturk, H., Saleem, S., Tarazona-Santos, E., Machado, L.R., Hollox, E.J. (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.

Pre-clinical and clinical development of antisense oligonucleotide-mediated exon skipping as a therapy for Duchenne muscular dystrophy (DMD)

Dr Karen Anthony in collaboration with Professor Francesco Muntoni at University College London and 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.  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.

Selected outputs:

  • Anthony K., Arechavala-Gomeza, V., Ricotti, V., Torelli, S., Feng, L., Janghra, N., . . . Muntoni, F. Biochemical characterization of patients with in-frame or out-of-frame DMD deletions pertinent to exon 44 or 45 skipping. JAMA Neurol. 2014:71(1);32-40.
  • Cirak, S., Feng, L., Anthony, K., Arechavala-Gomeza, V., Torelli, S., Sewry, C., . . . Muntoni, F. Restoration of the dystrophin-associated glycoprotein complex after exon skipping therapy in Duchenne muscular dystrophy. Mol Ther. 2012:20(2);462-467.
  • Anthony, K., Cirak, S., Torelli, S., Tasca, G., Feng, L., Arechavala-Gomeza, V., . . . Muntoni, F. Dystrophin quantification and clinical correlations in Becker muscular dystrophy: implications for clinical trials. Brain, 2011:134(12);3547-3559.
  • Cirak, S., Arechavala-Gomeza, V., Guglieri, M., Feng, L., Torelli, S., Anthony, K., . . . Muntoni, F. 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. 2011:378(9791);595-605.

Effects of unilateral lower limb eccentric training on neuromuscular and musculoskeletal 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 muscle strength, mass, balance and mobility in older people to promote healthy ageing and reverse functional decline in ageing.

Selected Outputs:

  • Kay AD, Rubley B, Talbot C, Mina MA, Baross AW, Blazevich AJ. Stretch imposed on active muscle elicits positive adaptations in strain risk factors and exercise-induced muscle damage. Scand J Med Sci Sports. 2018:28(11);2299–2309.
  • Kay AD, Fraser M, Hill M, Blazevich AJ. (2018). Effects of unilateral isokinetic eccentric training (and detraining) on musculoskeletal characteristics in older people. 23rd Annual Congress of the European College of Sport Science (ECSS), Dublin, Ireland, 04-07 July 2018.
  • Blazevich AJ, Kay AD. Stretching of voluntarily-activated muscles evokes greater acute and chronic adaptive changes than (traditional) static stretching. J Sci Med Sport. 2017:20(2);S41–S42.
  • Kay AD, Richmond D, Talbot C, Mina MA, Baross AW, Blazevich AJ. Stretching of active muscle elicits chronic changes in multiple strain risk factors. Med Sci Sport Exer. 2016:48(7);1388-1396.

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.

Selected Outputs:

  • 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. https://doi.org/10.1371/journal.ppat.1007052

Neuropathophysiology of Duchenne muscular dystrophy

Dr Karen Anthony, Amanda Ash

Duchenne muscular dystrophy (DMD) is a fatal childhood genetic disorder with no cure. It is caused by the body-wide absence of a muscle protein called dystrophin. Besides severe muscle wasting; the loss of dystrophin in the brain is linked to intellectual disability and psychiatric syndromes.  We aim to investigate the role of dystrophin in the brain with a view to therapeutically target the cognitive and behavioural symptoms of DMD.

Selected outputs:

  • 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.

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.

Selected outputs:

  • Baross AW, Somania Y, Brook RD, Milne K, McGowan C and Swaine I. 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.  2017:31(3);362-368.
  • Baross AW, Hodgson DA, Padfield SL, and Swaine IL. Reductions in Resting Blood Pressure in Young Adults When Isometric Exercise Is Performed Whilst Walking. J Sports Med. 2017 Volume 2017, Article ID 7123834, 6 pages.
  • Baross AW, Somania Y, Levy P, Zinszer K, Milne K, Swaine I and McGowan C. 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. 2017:22;1-7.

Working with the Centre

If you are interested in working with the Centre for Physical Activity and Life Sciences, please contact tony.kay@northampton.ac.uk.