On Friday 30th May, we held our 5th Annual Postgraduate Seminar Afternoon.
This is a great chance for the many and varied members of the Euan MacDonald Centre to get together to discuss their research, and an opportunity for the postgraduate students to gain experience in presenting their data and get invaluable feedback.
We all enjoyed an afternoon of excellent research talks, ending with a fascinating and entertaining keynote lecture by Professor Nick Hastie, Director of the Institute of Genetics and Molecular Medicine, University of Edinburgh.
We also presented three students with the Noel Hampton Award, a prize devised by Euan MacDonald Centre researcher David Hampton and his mother Francine, in memory of their late father/husband Noel. The prize was to reward PhD students or postdoctoral researchers who had really gone “above and beyond” in their research. The winners were (left to right in photo), Matt Livesey (2nd prize), Abigail Herrmann (1st prize) and Anna-Claire Devlin (3rd prize). Congratulations all!
Then it was time to socialise and meet other members over beer and pizza…
Below are short summaries of the postgraduate talks.
Ratko Radakovic: Apathy in motor neurone disease
Ratko Radakovic, a 2nd year PhD student working with Dr Sharon Abrahams and Prof. John M. Starr, is looking at apathy in various neurodegenerative diseases. Apathy is reported as a frequent symptom of MND. Ratko has developed a scale for assessing different subtypes of apathy, called the Dimensional Apathy Scale (DAS). It has been designed specifically to account for physical disability associated with MND. The DAS is a short, 3-subscale patient and carer questionnaire. Ratko found that the DAS is both reliable and valid at assessing apathy in MND with no associations with physical disability.
Phillipa Rewaj: Behind the curtain of dysarthria: the nature of language impairment in MND
Phillipa Rewaj, a speech and language therapist who recently completed her PhD supervised by Dr Thomas Bak and Dr Sharon Abrahams, spoke about her research investigating the nature of language impairment in MND. Traditionally communication impairment in MND has been thought to be solely due to the motor speech impairment ‘dysarthria’. However increasingly recognised cognitive changes and recent evidence from the literature has raised the possibility of more central processing deficits. Using a compilation of cognitive and linguistic assessments she found that 44% of the 25 MND patients with dysarthria tested in her study could also be classed as having a language impairment. Deficits in spelling, reading, naming, and grammatical comprehension were documented in the ‘linguistically impaired’ subgroup, in addition to varying severity of dysarthria. This research has potential implications for how we manage communication impairment in MND patients, particularly with regard to augmentative and alternative (AAC) communication strategies.
Nina Rzechorzek: Hypothermic neuroprotection in hPSC-derived cortical neurons: pre-conditioning the neuronal compartment to stress
Nina Rzechorzek, a 3rd year PhD student in Prof. Siddharthan Chandran’s lab, is exploring the effects of temperature on neuronal health. Therapeutic hypothermia protects the human infant brain from anoxia-driven injury, but cooling adults is more challenging – with potentially lethal side effects. Cooling engages a physiological response within neurons that promotes their survival. Molecular mechanisms underlying this effect are poorly understood, but they could hold the key to preventing adult neuronal death. Using cortical neurons derived from human pluripotent stem cells, Nina has found that cooling induces a predictable ‘cold-shock’ response, as described in other model systems. This was accompanied by developmental reversal of protein tau and mild activation of the unfolded protein response pathway – critical players in many neurodegenerative disorders. The same duration of cooling also protected the neurons from oxidative and excitotoxic insults, important mediators of acute and chronic neuronal injury. Cooling thus preconditions these neurons to stress and returns them to a more primitive state, making them resistant to injury and simultaneously ‘priming’ them for repair. With more detailed analysis, the goal is to define drug targets that can be manipulated in various neuronal subtypes, and tailored to specific disease phases for maximal therapeutic gain.
Yujie Yang: Genes Involved in Motor Neuron Development and Differentiation
The zebrafish is a model organism for developmental biology. Importantly, a high degree of conservation of genes implicated in neurodegenerative diseases makes the zebrafish also an excellent model to study motor neuron diseases. Therefore, it is important to improve our understanding of motor neuron development and axonal differentiation in this model. Yujie has conducted a standard mutagenesis screen on a transgenically labelled sub-class of dorsally projecting motor neurons. She recovered six mutants displaying reduced neuron numbers and/or impaired differentiation of motor axons. Yujie is currently verifying the specificity of these phenotypes and further characterising the signalling mechanisms involved. Causative candidate genes will be determined to facilitate subsequent functional analyses. Genes found in this study will lead us to a better understanding of the molecular and genetic aspects of motor neuron development, and ultimately may help us to study the mechanisms underlying the development of motor neuron disease.
Kosala Dissanayake: Intermediate syndrome in Organophosphate neurotoxicity: a model for sporadic ALS?
Kosala Dissanayake, a 3rd year PhD student in Prof. Richard Ribchester’s lab, illustrated how the model system of intermediate syndrome of organophosphate pesticide neurotoxicity could help our understanding of neurodegenerative diseases such as ALS. Organophosphate toxicity in humans demonstrates an immediate classic anticholinergic syndrome but this is followed by delayed respiratory failure with weakness in proximal muscle groups in some patients. Kosala has established that the main cause of acute cholinergic syndrome is through prolonged synaptic transmission due to inactivation of acetylcholinesterase enzyme at neuromuscular junctions (NMJ). She has also revealed that, surprisingly, the molecules primarily responsible for this prolonged transmission are mainly the metabolic breakdown products of the pesticide ingredients. In order to model delayed respiratory failure, she has utilized an ex vivo organ culture assay exploiting the preservation of NMJ in Wallerian degeneration slow (Wlds) mice. She has shown that the combination of pesticide ingredients and their metabolic breakdown products give rise to both paralysis and degeneration in this assay. These findings highlight the importance of metabolites of environmental toxins in mechanisms of chronic paralysis and neurodegeneration.
Abigail Herrman: Synapse Degeneration in Alzheimer’s Disease: Investigating the Synergistic Effects of Amyloid-Beta and Tau
[summary to be added]