EMC Postgraduate Research Day 2011
by Bilada Bilican
The second EMC Postgraduate Day was held on 24th of February, bringing together a wide range of activities on Motor Neurone Disease (MND) research conducted in Edinburgh.
It is increasingly recognised that understanding, and ultimately treating, neurodegenerative conditions requires a multidisciplinary approach. Reflecting this necessity, work presented by researchers from the Euan MacDonald Centre and affiliated institutions covered a broad range of research, from cellular and animal models of neurodegeneration to clinical neuropsychology. A brief summary of the research presented by each investigator follows.
Bilada Bilican gave a brief overview of protein abnormalities found in MND and described methods developed to use stem cells, in particular patient-derived stem cell-like cells, to study motor neurone vulnerability and associated proteinopathies in culture. The ability to generate specific neuronal populations from human embryonic stem cells in culture presents an unrivalled opportunity to study neurodegenerative diseases in detail, as neurons have unique cellular physiology compared to other cells thereby necessitating directed investigation of specific cell types in the elucidation of neurodegenerative pathology. Clare Puddifoot presented a detailed characterisation of these human stem cell-derived neurons. This included the demonstration that these cells exhibit the electrophysiological properties of neurons, a property essential for understanding changes in neuronal function in both development and neuropathology.
Fruit flies, with their ease of generation and tractable genetics, present another powerful tool for modelling complex molecular interactions in biology. Based on observations initially made in sporadic ALS cases, Simona Paro presented her work on characterisation of Adar2 mutant fruit flies, showing that the lack of this enzyme causes neurodegeneration coupled with movement defects. Using a genetic screen in fruit flies, she also identified a signaling pathway that can be regulated in order to rescue this defect - thereby implicating a cellular protein quality control mechanism called autophagy in the pathogenesis of ALS. Stuart Forrest described research that focuses on another fruit fly model of motor neuron degeneration based on inherited ALS causative gene VAPB and its protein interactor Sac1. He reported that depletion of VAPB or Sac1 both trigger similar neurodegenerative phenotypes, making these models a powerful comparative tool for studying the downstream pathways involved in neuronal loss.
Chantal Mutsaers reported work investigating molecular changes in muscle in Spinal muscular atrophy (SMA), a childhood form of motor neurone disease caused by deletion of the SMN1 gene. Adopting a proteomics approach, she compared muscle tissue from mutant and control mouse models of SMA and identified alterations in two distinct groups of proteins involved in both muscle development and function. Furthermore, Chantal reported that these mouse proteomics results were validated using human tissue samples, which suggests that this skeletal muscle intrinsic molecular pathology is a key event in SMA.
A subset of patients with ALS are known to show subtle difficulties in a range of cognitive functions, including language processing. Dina van der Hulst's research investigates these changes by means of a battery of neuropsychological tests, which includes analysis of language and information processing. The results presented indicated that ALS-patients have a specific deficit in tasks requiring the comprehension of action sequences.
Finally, Shuna Colville (MND Research Nurse) gave a presentation on the Scottish Motor Neurone Disease Audit, Research and Trials project (SMART). This project aims to audit current clinical practice and access to services, with respect to MND, in light of the recently published NHS Quality Improvement Scotland (QIS) standards. Shuna also reported that SMART is also building on the existing bank of clinical DNA samples for research purposes and ultimately intends to become involved in Clinical Trials.
The talks were followed by an evening reception where participants had the opportunity for further informal, collaborative discussions. Overall, the EMC Postgraduate Research Day provided a successful platform for bringing together a broad spectrum of ALS-focused activities in Edinburgh.
