Kosala Dissanayake

Lecturer in Veterinary Biomedical Sciences

Biography

Background

Kosala graduated from university of Peradeniya, Sri Lanka with a degree in veterinary medicine and animal science in 2007.  After short time in small animal and exotic animal practice in Sri Lanka, she moved to Scotland to do a masters in integrative neuroscience at university of Edinburgh (2010) before completing her PhD in neuroscience from the same university (2015). Her PhD project was to understand the neuromuscular transmission failure in organophosphorus pesticide toxicity in humans, under the supervision from Prof. Richard Ribchester and Prof. Michael Eddleston. Then she undertook a post-doctoral research project looking at further mechanisms of her PhD research project (2015 – 2020).

Following a brief post-doctoral project with Prof. David Wyllie and Prof. Peter Kind at university of Edinburgh (2021- 2022), Kosala became a lecturer in Veterinary Biomedical Science at the Royal (Dick) School of veterinary studies in 2022.   

Her current research focuses are on calcium (Ca2+) induced excitotoxicity in neuromuscular junction. She is also interested in comparative neuromuscular junction physiology in large animals including companion animals and farm animals.   

Qualifications

2015 Doctor of Philosophy (PhD). University of Edinburgh

2010 Master of Science (MSc by research). University of Edinburgh

2007 Bachelor of Veterinary medicine and Animal Science (BVSc). University of Peradeniya, Sri Lanka

Responsibilities & affiliations

Animal Body 3 course organiser

Principle investigator  - Euan MacDonald Centre for Motor Neurone Disease Reasearch

Undergraduate teaching

Year 1 : Animal body 1

Year 2 : Animal body 3 & Animal Body 4

Year GEP : Animal body

Year 3 - 5 : Student research component 

Open to PhD supervision enquiries?

Yes

Areas of interest for supervision

Physiology of neuromuscular junction transmission in health and disease. 

Current research interests

Synaptic vulnerability to excitotoxicity may be a common pathway to neurodegeneration in many neurodegenerative diseases, including motor neuron diseases such as Amyotrophic Lateral Sclerosis (MND/ALS), Alzheimer’s disease, Parkinson’s disease and Huntington disease. Therefore, understanding how excitotoxicity contributes to synaptic vulnerability and preventing it may help to prevent or retard the progression of these devastating diseases in the long run. Ca2+ dependent excitotoxicity leading to neuronal cell death is one of the common pathways hypothesised at both glutamatergic and cholinergic synapses. Therefore we are investigating how normal handling of intracellular Ca2+ is altered by excitotoxic triggers and, specifically, test the hypothesis that excitotoxicity at NMJs depends on either cytoplasmic increases in Ca2+ ions due to their release from the sarcoplasmic reticulum (Ca-induced Ca-release via ryanodine receptors) or failure to initiate relaxation (Ca2+ removal from cytoplasm via SERCA). I will use pharmacological interventions to separate out the fast and slow Ca2+ transients, in order to identify whether post-tetanic Ca2+ surges depend on either CaV 1.1 or dihydropyridine receptors (DHPRs) and ryanodine receptors, or DHPR and inositol trisphosphate receptors (IP3Rs). Alternatively, promoting initiation of relaxation via SERCA or other mechanisms (uptake via sarcolemmal Ca2+ transport proteins and mitochondrial uniporter) would results in reduction of Ca2+ surges. I will explore the possible pathways of Mg2+ mitigation of Ca2+. Finally, we are also investigating evidence for Ca2+ dependent excitotoxicity and degeneration by looking at human post-mortem in samples pesticide toxicity cases.

Past research interests

The focus of my previous postdoctoral research was to understand the failure of neuromuscular transmission that occurs following ingestion of organophosphorus (OP) insecticides, responsible for over 200,000 deaths per annum, predominantly in rural Asia. My studies have shown that cyclohexanol, a solvent metabolite of a key agricultural insecticide formulation, dimethoate EC40, acts conjointly with the OP metabolite omethoate, compromising synaptic transmission at neuromuscular junctions (NMJs) and causing neuromuscular paralysis. We found that the effect of cyclohexanol was strongly temperature dependent, which also identified a possible treatment, namely, targeted temperature management (induced hypothermia) as an adjunct to existing treatments. We showed that lowering body temperature in an OP intoxicated pig model mitigates cyclohexanol-induced neuromuscular paralysis. A clinical trial is being instigated. We also identified Mg2+ as a potential adjunct to treatment of toxicity induced by organophosphorus anticholinesterases.

View all 13 publications on Research Explorer

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