"Early intervention is critical to preventing the devastating symptoms seen in Parkinson’s disease. My lab focuses on the thing that makes neurons special, chemo-electric signal transduction and temporal encoding. We will look at the progression of the disease over time to understand how and when this communicative role between neurons breaks down." Dayne Beccano-Kelly
UK DRI Group Leader
Dr Dayne Beccano-Kelly obtained his BSc (Hons) in Biochemistry (with Industry) from the University of Leeds in 2006, before going on to complete my PhD on the relationship between stroke and Alzheimer’s disease (AD). Both his undergraduate degree and PhD included an educational/professional placement at the Mayo clinic in Jacksonville, Florida working with human tissue under the direction of Dr. Dennis Dickson. He subsequently went on to investigate the potential neuro-protective effects of the feeding hormone leptin in Alzheimer's disease at the University of Dundee, Scotland, before becoming a senior post-doctoral fellow at the University of British Columbia (Canada) Centre for Applied Neurogenetics (CAN). Here he worked on the longitudinal characterisation of genetically faithful parkinsonian models in an attempt to isolate changes in synaptic function over time in disease. In 2015, Dr Beccano-Kelly joined the University of Oxford as a Parkinson’s UK Career Development Fellow. Using human iPSCs as a model and with a focus of electrophysiology and calcium imaging as tools, he identified robust phenotypes relating to synaptic function and energy. In 2020, Dr Beccano-Kelly won the prestigious Future Leader Fellowship allowing him to carry out his work on early synaptic health in Parkinson’s disease as a Group Leader based at UK DRI at Cardiff from February 2021.
1. At a glance
Parkinson’s is the fastest growing neurological condition and the second most common neurodegenerative disorder - around 145,000 people live with the condition in the UK. Current therapeutics only treat symptoms so a means to prevent the onset of Parkinson’s is essential. In the past, research has focused on the late stages of Parkinson’s, but evidence suggests that how the job of neurons breaks down before significant brain cell loss, would provide the best chance of preventing the clinical symptoms of Parkinson’s. Dr Dayne Beccano-Kelly and his team study communication between brain cells using research models of Parkinson’s, with the aim of deciphering what goes wrong early in Parkinson’s and how it can be corrected.
2. Scientific goals
In Parkinson’s Disease (PD), the loss of dopaminergic neurons of the substantia nigra pars compacta (SNpc) is attributed to the classic clinical symptoms observed in the disorder. Research has typically been carried out on late-stage pathologywith these works yielding important insights into cell death. However, the most common prescribed treatment, L-DOPA, loses its effectiveness over time, does not prevent further degeneration and can provoke new symptoms. These outcomes are likely a result of targeting the late stages of PD i.e. loss of neurons, rather than the preceeding dysfunction and abberent mechanism. (Beccano-Kelly et al., 2015; Janezic et al., 2013; Matikainen-Ankney et al., 2016; Volta et al., 2017; Yue et al., 2015).
This programme aims to identify the early changes in neuronal function that can be targeted to prevent clinical symptoms of PD. The team focus on longitudinal assessment of genetically faithful models of PD, and assesses the chemo-electric communication and signal transduction of neurons and the molecular functions which directly impact this critical specialised role. This will provide data on the neuronal dysfunction which likely results in the susceptibility seen in PD. Two critical questions in the field of PD research are being addressed: Which phenotypes should be corrected and critically, when? This approach facilitates the unmet need for effective therapies via understanding of the temporal nature of PD.
Main objectives and research goals
- Determine the progression of synaptic phenotypes in PD hiPSC DA neurons over time.
- Investigate the longitudinal progression of synaptic phenotypes in genetic PD mouse models.
- Elucidate the restorative potential of early pharmaceutical intervention in PD on neural network/synaptic dysfunction.
- Validate synaptically related phenotypes in multiple major mutation and sporadic PD lines
- Identify early network dysfunction in human PD
3. Team Members
Dr David (Harri) Harrison (Research Associate)
Dr Shiva Kompella (Research Associate)
Within UK DRI:
- Prof Caleb Webber, UK DRI at Cardiff
- Prof. Vincent Dion, UK DRI at Cardiff
Beyond UK DRI:
- Prof. Birgit Liss, University of Ulm, Germany
- Prof. Mark Walton, University of Oxford
- Dr. Mattia Volta, European Academy, Bolzano, Italy
- Prof. Michele Hu, University of Oxford
- Prof. Matt Farrer, University of Florida
- Dr Dave Smith, AstraZeneca
Parkinson’s Disease, Neurodegeneration, iPSC models, Synaptic Function, Disease Temporality, Electrophysiology,
Electrophysiology, Immunocytochemistry, Behaviour, Photometry, Optogenetics, Molecular Biology