Wellcome Trust Centre For Mitochondrial Research

Dr Brendan Payne

Personal Biography

I undertook my undergraduate medical training at the University of Nottingham, graduating in 2002 with BMedSci (1st class) and BMBS (with honours). I then moved to Newcastle for postgraduate training in General Internal Medicine (MRCP, 2005), followed by specialisation in Infectious Diseases. I am dual CCT accredited in Infectious Diseases and Medical Virology (FRCPath, 2014).

My doctoral research training was in the laboratory of Professor Patrick Chinnery in the Institute of Genetic Medicine at Newcastle University, funded by personal fellowships from the British Infection Association and the MRC (PhD, 2014). During this time I undertook the initial work characterising somatic mitochondrial DNA mutations in the setting of anti-retroviral therapy for HIV infection.

Since completion of my clinical training (2015), I have worked as a Clinical Academic within the Wellcome Centre for Mitochondrial Research. My clinical and research interests focus on the long-term health of people living with HIV and specifically, the role that acquired mitochondrial dysfunction plays in this.


Research Project

The Molecular Basis of Ageing in HIV Infection

Principal Investigators: Dr Brendan Payne

Other staff members involved: Laura Greaves, Amy Vincent, Carla Roca Bayerri, Megan McNiff and Matthew Hunt.

Project details

My lab undertakes a combination of clinical and basic laboratory studies, with the overall aim of better understanding the role of mitochondrial DNA mutations in the interplay of ageing and HIV.

  • The role of acquired mitochondrial dysfunction in ageing with HIV. We have previously demonstrated an excess of mtDNA mutations in some people living with HIV (PLWH), in an apparent acceleration of the process seen in normal human ageing. Current studies collect tissue samples from PLWH, especially skeletal muscle. We measure mitochondrial dysfunction at the cellular and molecular level in tissue, alongside physical function in patients. Our work to date suggests that some PLWH have myofibres with defects of mitochondrial respiratory chain complexes (especially complex I). These defects correlate with ageing phenotypes, including frailty. We have previously shown that a ‘legacy effect’ of prior exposure to mtDNA polymerase γ inhibiting anti-retroviral therapy (ART) is a major driver of these acquired mitochondrial defects. Current work attempts to delineate other causal pathways. Overall this programme of work aims to understand potential modifiers of healthy ageing in PLWH.
  • Modelling the natural history of mtDNA mutations. The natural history of mtDNA mutations within cells is critical to the expression of functional mitochondrial defects. It is widely suggested that the clonal expansion of pre-existing mtDNA mutations within cells is more relevant than mutagenesis in both ageing and HIV/ART. Modelling clonal expansion is technically challenging but potentially highly tractable, especially for testing potential therapeutic strategies. We are therefore developing mouse models of clonal expansion and assessing the effects of ART and other interventions on the expression of mitochondrial dysfunction.
  • Multisystem mitochondrial damage in HIV infection. Although skeletal muscle is the ‘prototype’ tissue in which to study mitochondrial defects, it is recognised that inherited mitochondrial diseases and ageing are multisystem processes. As such, we expect that acquired mitochondrial dysfunction may be present in multiple tissues in PLWH. We have previously demonstrated mtDNA deletions in the urinary epithelium of PLWH, associated with ART-induced renal tubulopathy. We are currently performing studies on post-mortem brain from PLWH in order to define the presence and determinants of acquired mitochondrial defects. This may be important in understanding the excess of mild cognitive impairment seen in otherwise successfully treated PLWH. As ART-treated PLWH also show features of ‘immune-ageing’, we are developing approaches to studying mitochondrial dysfunction in parallel with T-cell phenotype.

Sponsor/funder: Wellcome Postdoctoral Research Training Fellowship for Clinicians, Wellcome Centre for Mitochondrial Research, British HIV Association.

Publications: https://www.ncl.ac.uk/ion/staff/profile/brendanpayne.html#publications

Contact: Brendan.Payne@ncl.ac.uk